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It has been found out that methylation of nucleic acids, proteins and low-molecular substrates is necessary to renew cellular structures, their restoration and cytoprotection. Methionine plays the most important role in this process but whether its metabolism changes during anesthesia and how different anesthetics affect it, has not yet been studied. The objective : to study the metabolism of methionine during cardiopulmonary bypass when the direct myocardial revascularization is performed and the impact of the anesthetics used (propofol, desflurane, and sevoflurane) on methionine metabolism. Subjects and methods : 74 patients who underwent surgery due to coronary heart disease with cardiopulmonary bypass were enrolled in the study. The patients were divided into three groups by the anesthetic used (desflurane, sevoflurane, propofol). Levels of methionine, homocysteine, cysteine, and taurine were tested in the blood collected from veins and jugular vein before the aorta clamping and after the release of clamps. Results . In all three groups, lower levels of methionine and a higher level of homocysteine were observed after the release of clamps from the aorta, especially in the jugular vein. The most significant consumption of methionine was noted when propofol was used. In the same group, the exocytic release of homocysteine into the blood and the formation of cysteine were significantly lower. No significant difference was observed in the effect of desflurane and sevoflurane on methylation. Conclusion . During the anoxia, the consumption of methionine increases significantly but the intensity of demethylation/remethylation depends on the anesthetics used during anesthesia. The most significant decrease in the level of methionine as well as the remethylation of homocysteine into methionine occurs with the use of propofol, rather than inhalation anesthetics which may be a consequence of desflurane and sevoflurane cytoprotective properties.

Introduction. Under the conditions of circulatory disorders and coronary heart disease (CHD), amino acids acquire additional value as a source of intermediates of Krebs cycle, participating in cell energetics. If there is a disturbance of energy metabolism, the level of amino acids in the blood can change, including the minor non-encoding amino acid homoarginine (hArg).The objective of this study was to compare the shifts in the levels of hArg and other amino acids in the venous blood flowing from the tissues of the heart and brain versus their levels in blood plasma from the cubital vein in patients with CHD.Methods and materials. The study used plasma samples of 58 patients (46 men and 12 women) aged 62 (57 — 66) years with CHD and heart failure of functional class III (NYHA). The level of hArg and the spectrum of 22 other amino acids were determined by the reversed-phase high-performance liquid chromatography (HPLC). Besides, the levels of lactic acid (LA) were determined by spectrophotometric method, as well as routine biochemical parameters were determined using standard kits.Results. Patients with CHD had compensated, without significant deviations, biochemical data of glucose level, lipid and nitrogen metabolism profiles. The level of hArg in the patient group of 1.4 (1.0—1.9) p.M was significantly lower compared to the reference interval, and the level of total homocysteine was increased, although there were no differences depending on the venous basin. The highest concentrations of LA, alanine and glutamine were detected in the plasma from the internal jugular vein. At the same time, lower concentrations of arginine, lysine and alanine corresponded to the lowest values of hArg.Conclusion. In patients with CHD and heart failure, a significant increase in the levels of glutamine and alanine in plasma from the internal jugular vein and coronary sinus in comparison with plasma from the cubital vein was accompanied by profound dysregulation of energy metabolism with the decrease in hArg levels.

According to current data, a low level of folic acid (FA) contributes to the progression of arterial hypertension (AH), affecting the metabolism of cells that are involved in the vascular tone regulation, such as hypothalamic astrocytes of nervous tissue. It is also known that the level of FA in the nervous tissue and cerebrospinal fluid is 2-3 times higher than in plasma. There is another metabolic marker of cardiovascular diseases, the level of plasma homoarginine (hArg). The decrease in the level of plasma hArg is also known as a diagnostic sign. In our study, we established that in patients with AH (n = 60), the level of hArg was almost 2 times lower than in healthy individuals, and in 75% of cases the rate was below 1.80 μM. The insufficiency of FA taking into account its low level in plasma FA, as well as the level of total homocysteine (tHcy) higher than 10.9 μM, was observed in 78% of patients. HArg levels at values less than 1.80 μM corresponded to a statistically significant decrease in FA when its content was less than 13.5 nM. This relationship (r = 0.63, p = 0.020) appears in patients with AH, regardless of the number and severity of target organ damage (TOD). FA and hArg as metabolic markers exhibit various diagnostic capabilities when comparing subgroups of patients without TOD and with multiple TOD. Significant differences fared at an acceptable level (p = 0.007) only for the hArg levels, while for the FA concentrations there was only a trend to decrease. It is possible that metabolic disturbances in the central nervous system that are associated with the necessary to maintain high FA concentration contribute to the development of hypertensive status. The causal relationship of a parallel decrease in hArg and FA levels in patients with AH requires further research.

The level of homoarginine (hArg) in terms of prognostic significance may exceed the natriuretic peptides and other well-known markers according to the latest data about the progression of cardiovascular diseases. The lack of data on the association of hArg levels with levels of other metabolites makes it difficult to understand its role in the pathogenesis of cardiovascular diseases. Relationships of hArg and other amino acids, including methionine (Met) and total homocysteine (tHcy), and their ratio in patients with ischemic heart disease were evaluated. The study included 74 patients with coronary heart disease (57 men and 17 women) aged 62 (57 - 67) years before coronary artery bypass surgery and 27 healthy people of similar age. In patients, the level of hArg was almost 2 times lower (p

A large number of studies have established a link between the progression of arterial hypertension (AH) and folic acid (FA) deficiency. Due to the deficiency of FA, an increase in the level of total homocysteine (tHcy) is observed. The cut-off point for total homocysteine (tHcy), which is not associated with the toxic effect of Hcy itself, indicating the increase in FA deficient state, has not been clearly defined to date. The purpose of this work was to assess the cutoff value of tHcy applied to assesment of functional FA deficiency in hypertensive patients, including group with chronic kidney disease (CKD). Material and methods. The study included blood samples from 60 hypertensive patients aged 61 (45-70) without (N=31) and with (N=29) diagnosed kidney disease and also samples from 30 healthy donors. Clinical and biochemical data, including tHcy, FA and vitamin B12 of blood plasma were assessed. Results and conclusion. Hyperhomocysteinemia in patients with CKD was significantly higher than in patients without CKD. The level of tHcy in all patients was inversely correlated with the level of FA in the blood plasma. Some patients without a deficiency of FA and B12 had an increased level of tHcy, which indicated a functional deficiency of FA. Another situation in few patients without functional deficiency of FA was observed, in which the decreased FA level without increasing level of tHcy established. Frequently used cutoff point for hyperhomocysteinemia above 15 μM indicates the starting point of tHcy concentrations associated with the toxic effects of Hcy by itself. To determine the functional deficiency of FA in the absence of its deficiency in the plasma, the cutoff level of tHcy from 10.9 µM should be used.

Introduction.In systemic autoimmune diseases with joint damage (SADJD), impaired angiogenesis occurs, which plays a key role in the progression of proliferative synovitis and in the development of lesions of the internal organs. Excessive production of vascular endothelial growth factor VEGF-A, the main mediator of angiogenesis, leads to an increase of the inflammatory process.The objectiveof the work was to study the relationship of VEGF-A with glutathione metabolism parameters, activity of the process and immune status in systemic autoimmune diseases with joint damage.Material and methods.58 patients with systemic autoimmune diseases with joint damage were examined. The comparison group consisted of 45 healthy individuals. The main clinical parameters and rheumatoid factor (RF) were analyzed. To determine the activity of the process, we calculated the indices DAS28 for patients with rheumatoid arthritis (RA) and BASDAI for patients with ankylosing spondylarthritis (AS). The activities of the enzymes glutathione peroxidase (GPO), glutathione reductase (GR), superoxide dismutase (SOD) and the content of GSH were determined in erythrocytes.Results. The level of serum VEGF-A in patients with systemic autoimmune diseases with joint damage was increased more than 30 %, in erythrocytes the concentration of GSH and GPO activity were 2 times lower and almost 2 times lower respectively, and GR activity was reduced by about 20 % compared with donors. A correlation was found between the level of VEGF-A and GR activity (R = 0.579; P = 0.03) in RA patients with moderate activity of the process, and absence of relationship between these parameters and the activity of the process in AS. The activity of both GPO and GR in patients with RF was lower by more than 1.5 times, and SOD activity was twice lower than control. The VEGF-A level in the blood plasma was determined by the method of non-competitive enzyme immunoassay.Conclusion.The increase in VEGF-A level in the blood plasma of patients with systemic autoimmune diseases with joint damage is most pronounced in RA patients with moderate activity of the process and is associated with the presence of RF. The relationship of VEGF-A and GR activity indicates a special role for this enzyme in the regulation of angiogenesis in RA.

Aim . To assess the safety of the application of high-dose atorvastatin and its effect on metabolic parameters, such as the total level of nitric oxide and homocysteine in the blood plasma in patients with ischemic heart disease during a coronary artery bypass surgery (CABG). Material and methods . The study included 42 patients with stable effort angina II-IV functional class. A special criterion for selection was the taking atorvastatin at a dose of 20 mg/day for at least 30 days before patient was directed to surgical revascularization of the myocardium. Immediately before the intervention, the dose of atorvastatin was increased to the maximum allowed with subsequent taking of 40 mg/day. Complications after CABG, indicators of lipid metabolism and biochemical safety of statin use were analyzed. The duration of observation of results of the acute atorvastatin recapture therapy was 3 weeks during hospital period. We used modern enzymatic method for nitrogen oxides determination with the application of nitrate reductase. Determination of total homocysteine was performed by high performance liquid chromatography. Results. It was found that atorvastatin 80 mg for 12 hours and 2 hours before CABG in patients previously treated with atorvastatin 20 mg/day is well tolerated and leads to decrease in total levels of nitric oxide by 1.6 (0.18-10.8 ) μmol/l and homocysteine by 0.9 (0.17-2.69) μmol/l (p< 0.05 for both) Conclusion. It is assumed that the metabolic effects of high-dose therapy with atorvastatin may have a positive influence on the immediate postoperative period.

In the analysis of plasma amino acid profile in a group of patients with left ventricular outflow tract pathology (n = 151) increased levels of serine, alanine, arginine, and lysine has been found. These metabolic shifts can be linked with the development of circulatory deficiency and mitochondrial dysfunction. The differentiation of the reference values intervals helps in the assessment of individual amino acid profiles.

Patients with abnormal left ventricular outflow tract had middle lactic acidemia with detected cytochrome C release into the bloodstream and liberation of protein PGC1a (peroxisome proliferator-activated receptor gamma coactivator-1alpha) with elevation its blood concentration reflecting mitochondrial biogenesis in tissues.

Background: Ascending thoracic aortic aneurysm (aTAA) is a heterogeneous group of disorders that involve impaired endothelial function. The nitric oxide (NO) synthase inhibitor asymmetric dimethylarginine (ADMA) serves as an endothelial dysfunction marker. Thus, we investigated ADMA levels in patients with aTAA. Methods: Eighty-six patients with aTAA and 18 healthy individuals were enrolled. All patients underwent echocardiography. Plasma ADMA levels were measured using high-performance liquid chromatography. Results: ADMA levels were higher in aTAA patients than in control patients (p = 0.034). According to the multivariable regression model, higher ADMA levels were associated with ascending aortic diameter (p = 0.017), smoking (p = 0.016), and log-transformed estimated glomerular filtration rate (eGFR, p = 0.005). Conclusion: This pilot study demonstrates an association of ADMA with ascending aortic dilatation; however, further studies are needed to investigate whether increased ADMA levels underlie aTAA development.

The level of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC1α) in human blood plasma was investigated. Samples of healthy individuals (n=34) and patients with cardiovascular diseases (n=110), including aortic aneurysm (n=69), aortic stenosis (n=25) and patients without aortic pathologies were analyzed. In patients the PGC1α concentration was higher than that in healthy persons, and tended to decrease with age. Elevated concentrations of lactic acid, total homocysteine and asymmetric dimethylarginine in the blood of patients suggested a parallel development of endothelial and secondary mitochondrial dysfunction. However, concentrations of lactic and pyruvic acids exceeding reference limit were associated with the decrease in the PGC1α level.Vpervye provedeno issledovanie urovnia belka PGC1a (1a-koaktivatora gamma-retseptora, aktiviruiushchego proliferatsiiu peroksisom) v plazme krovi. Issledovany obraztsy zdorovykh lits (n=34) i patsientov s serdechno- sosudistymi zabolevaniiami (n=110), v tom chisle s anevrizmoĭ aorty (n=69), s aortal'nym stenozom (n=25) i bez patologii aorty. V gruppe patsientov kontsentratsiia PGC1a byla vyshe, chem u zdorovykh lits, i imela tendentsiiu k snizheniiu s vozrastom. Povyshennye kontsentratsii molochnoĭ kisloty, obshchego gomotsisteina i asimmetrichnogo dimetilarginina v krovi patsientov svidetel'stvovali o parallel'nom narastanii éndotelial'noĭ i vtorichnoĭ mitokhondrial'noĭ disfunktsiĭ. Na fone kontsentratsiĭ molochnoĭ i pirovinogradnoĭ kislot vyshe referentnykh znacheniĭ obnaruzheno snizhenie kontsentratsii PGC1a.

Blood carboxypeptidases play an important role in the regulation of fibrinolysis. We have proposed here the method for the assay of blood carboxypeptidase activity associated with coagulation/fibrinolysis using the natural substrate fibrin and the detection of basic amino acids arginine and lysine as products under conditions closely resembling those in vivo. Plasma samples from 15 patients with arterial hypertension have been investigated. Coagulation and subsequent fibrinolysis were initiated by addition of standard doses of thrombin and tissue plasminogen activator, respectively. Arginine and lysine concentrations before, during, and after completion of fibrinolysis were determined using HPLC. The parameters of fibrinolysis were evaluated by the clot turbidity assay. The coagulation/fibrinolysis cycle was accompanied by a significant increase in concentrations of arginine and lysine in the incubation mixture by 101 and 81%, respectively. The duration of fibrinolysis initiation significantly correlated with the degree of increase of these amino acids: rS = −0.733 and −0.761 for arginine and lysine, respectively (p < 0.05). Arginine generation had two maximums: one in the beginning of clot lysis and another one at the end of the lysis, whereas the lysine release occurred mainly in the middle of fibrinolysis. Thus, the carboxypeptidase activity associated with fibrinolysis can be considered as a local source of the essential amino acids originated from fibrin clot degradation products.