[Analysis of the causes of repeat stenosis of the coronary arteries after elective stenting in patients with stable angina pectoris].

AIM: Coronary stenting is the evidence-based treatment approach of stable angina. The objective was to determine the incidence of restenosis or atherosclerosis progression which led to the need for coronary angiography according to a single center registry data. MATERIALS AND METHODS: The procedure and clinical data of 3732 (2897 males) consecutive stable coronary artery disease patients undergoing coronary stenting, over five years between March 2010 and September 2014, were subject of this study. Over the next 4 years, 1487 (1173 males) patients were re-evaluated due to angina reoccurrence. 699 patients demonstrated the indications for coronary angiography. RESULTS: The restenosis of the previously stented segment was detected in 84 (12%) cases, the progression of coronary atherosclerosis in 306 (44%), the combination of restenosis and atherosclerosis progression in 63 (9%), and the absence of these complications in 245 (35%) cases. The progression of coronary atherosclerosis was the leading indication for the repeat angiography and revascularization (44 and 58%, respectively); p0.05. The basal level of hsCRP2 mg/l had a prognostic significance for the development of combined event (the restenosis and atherosclerosis progression): AUC 0.65 (0.500.75), OR 3.0 (1.17.9), p0.05. CONCLUSION: The progression of coronary atherosclerosis was the leading indication for the repeat angiography and repeat revascularization during 2 years after coronary stenting. The hsCRP level 2 mg/l at baseline had a prognostic significance for the development of restenosis in previously stented segment and coronary atherosclerosis progression.

[Affine Haemosorbents Based on Aromatic Peptides for Binding of the Immunoglobulin G].

Affinity haemoadsorbents based on WY, WTY, WNY ligands and polysaccharide matrix were developed for the human immunoglobulin G binding. The characteristics of new sorbents such as the binding of total IgG and binding of IgG subclasses were compared. It was found that all new sorbents well extract the IgG from the blood plasma. It was evidenced that WNY-based sorbent is more effective for binding of IgG subclass 3. The determination of physic-chemical characteristics of IgG binding revealed that desorption constants for IgG are 10 ± 3, 28 ± 4 and 13 ± 3 µM for WY, WTY, WNY based sorbents respectively. Maximum sorption capacities for IgG are 43 ± 2, 45 ± 3 and 46 ± 3 mg IgG per ml of sorbent for WY, WTY, WNY based sorbents respectively. Also it was shown that the new sorbents are compatible with blood and are suitable for the medical purposes.

[The different notions about beta-oxidation of fatty acids in peroxisomes, peroxisomes and ketonic bodies. The diabetic, acidotic coma as an acute deficiency of acetyl-CoA and ATP].

The mechanisms of beta-oxidation of fatty acids developed more than a century before have no compliance with actual physical chemical data. The oxidation of long-chain C 16:0 palmitic saturated fatty acid occurs not by sequential formation of eight molecules of acetyl-KoA but by force of formation of double bond and its hydrolysis on two short-chain C 8:0 fatty acids. Only short-chain fatty acids can become shorter under "chipping" of C 2-acetate with formation of C 4-butyric acid (butyrate) and its metabolites (beta-hidroxibutirate, acetoacetate, acetone). The critical moment of oxidation is a hydrolysis of acetoacetyl-KoA on two molecules of acetyl-KoA. The molecule of ATP is to be expended on hydrolysis. The foundation of nonspecific biological reaction of stress--ketoacidosis,--is a decrease in mitochondrions of acetyl-KoA pool formed both from glycogen and glucose and fatty acids. The oxalate acetate inputs into Krebs cycle inadequate amount of acetyl-KoA which limits synthesis of ATP. The insulin has no direct involvement into development of ketoacidosis but prepares conditions to facilitate nonspecific etiological factor to initiate diabetic ketoacidosis. These are the pooling of small amount of glycogen in cytozol and the predominance in cytozol of cells and adipocytes of palmitic triglycerides which are slowly hydrolyzed by hormone-dependent lipase to release non-esterified fatty acids into intercellular medium. The increase of their concentration in blood plasma precedes ketoacidosis which is developing in patients without diabetes mellitus too. When cells begin to oxidize unsaturated linoleic and linolenic acids with large number of double binds instead of medium-chain fatty acids, oleinic and palmitic fatty acids to support beta-oxidation in mitochondrions and synthesis of ATP the amount of butyric acid, beta-hidroxibutiryl-KoA and acetoacetyl-KoA increases and of acetyl-KoA decreases. The cause of fatal outcome is the development of metabolic acidosis, hyperhydration of cerebral cells with development of edema and a physiologic respiratory compensation of metabolic acidosis. The decarboxylation of acetoacetate and formation of acetone--initial stage of gluconeogenesis--formation of glucose from fatty acids--is manifested poorly both in primates and humans. From theoretical positions, to arrest ketoacidosis and to restore synthesis of AFT, it is reasonable to apply the infusion of optimal amount of acetyl-KoA which as nonpolar tioester can get over hematoencephalic barrier, plasma membrane and inner membrane of mitochondrions. It is supposed that diabetes mellitus is to be considered primarily as pathology of metabolism of fatty acids and only secondly as pathology of glucose.

[The fatty acids in blood plasma and erythrocytes in test of glucose tolerance].

The sample of 26 patients with ischemic heart disease and syndrome of insulin resistance was subjected to standard test of glucose tolerance. The content of individual fatty acids was detected using technique of gas chromatography and mass spectrometry. In blood plasma, after 2 hours of post-prandial hyperglycemia, reliably decreased content of C 16:1 of palmitoleic mono fatty acid, C 18:1 oleic mono fatty acid and in a lesser degree C 18:2 linoleic unsaturated fatty acid (p < 0.05). The level C 14:0 of myristic unsaturated fatty acid, C 16:0 of palmitic unsaturated fatty acid and with 18:0 of stearic unsaturated fatty acid, ratio C 16:0/C 16:1 and C 18:0/C 18:1 had no changes: content of both (omega-6 C 20:3 digomo-gamma-linoleic unsaturated fatty acid and essential polyenoic fatty acids remained the same. The significant differences between initial content in blood plasma of palmitic saturated fatty acid and oleic monoenic fatty acid was noted. The alteration in content of fatty acids in membranes of erythrocytes is the most expressed. In erythrocytes reliable (p < or = 0.05) decrease of content of C 16:0 palmitic fatty acid, C 18:0 stearic fatty acid and C 18:1 oleic fatty acid is established. The reliable decrease is noted in content of linoleic unsaturated fatty acid. In erythrocytes, moderate decrease is detected in levels of C 20:4 arachidonic polyenoic fatty acid, C 20:5 eicosapentaenoic polyenoic fatty acid. It is assumed that under post-prandial hyperglycemia insulin regulates metabolism of fatty acids, blocks lipolysis, decreases in cytosol of cells content of oleic and palmitic fatty acids inform of acetyl-KoA and forces mitochondrions intensively oxidate acetyl-KoA formed from pyruvate, from GLU. On surface of membrane, insulin increases number of glucose carriers GLUT4. Hypoglycemic effect of insulin is mediated by regulation first of all of metabolism of fatty acids. Hyperglycemia and insulin are two phylogenetically different humoral regulators. Insulin initiates blockade of lipolysis in adipocytes and positioning on membrane GLUT4. Hyperglycemia passively (activated) increases absorption by cells GLU on gradient of concentration inter-cellular medium--cytosol and synthesis of glycogen.

[The positional isomers of triglycerides in oils, fats and apoB-100 lipoproteins: palmitic and oleic modes of metabolism of fatty acids-substrates for energy acquiring].

Even total resemblance of content of fatty acids in triglycerides has both no standing for their functional unity nor even identity of their physical chemical characteristics. The etherification of fatty acids in various positions of three-atomic glycerin separates triglycerides on palmitic and oleic substrates for energy acquiring by cells. The kinetic parameters of biochemical reactions under palmitic mode of metabolism of fatty acids are always low. The myocytes in biological reaction of exotrophy experience deficiency of exogenous fatty acids which in vivo is to permanently supply through activation of biological reaction of endotrophy--enhancement of lipolysis in adipocytes. The biological role of insulin is to prevent formation in vivo of palmitic mode of metabolism of saturated and monoenic fatty acids. Under this condition, the necessity to activate lipolysis and to increase in blood plasma concentration of unesteritied fatty acids forms syndrome of resistance to insulin. The surplus of palmitic fatty acid in food and deficiency of insulin show in vivo unidirectional a physiologic action. The formation of palmitic mode of metabolism of energy substrates--portion of pathogenesis of atherosclerosis, metabolic syndrome, obesity, non-alcoholic fatty infiltration of liver and partiallly essential arterial hypertension.

[The difference of conformation of apoB-100 in lipoproteins of low and very low density. The modified lipoproteins and destructive inflammation in intima of arteries: a lecture].

The formation of ligand occurs in phylogenetically earlier lipoproteins of very low density and later lipoproteins of very low density when apoB- 100 takes active conformation in association with essential polyenoic fatty acids, in form of ethers with alcohol cholesterol, palmitic and oleic triglycerides. In lipoproteins of low density apoB-100-domain-ligand is formed, in lipoproteins of very low density apoE/B-100-ligand is formed. The ligand lipoproteins absorb cells using apoE/B-100 and apoB-100 receptor endocytosis. In cases of excess of palmitic triglycerides. and lipoproteins of very low density of the same name in blood, damage of primary structure of post-heparin, hepatic lipoprotein lipase and co-enzymes apoC-II and apoC-II, phenotype E2/E2 blood accumulates pre-ligand lipoproteins rich in triglycerides. In case of pathology of apoB-100-receptor post-ligand lipoproteins of low density with low content of triglycerides are cumulated. All non-ligand lipoproteins in a physiological way denature neutrophils. The presence of pathology induces modification in case of action of other agents (glyco-toxins). The pre-lipoproteins form in the intima of arteries soft voluminous plaques and such destructive inflammatory process as athero-thrombosis. The post-lipoproteins form flat plaques and destructive inflammatory atheromatosis. The atherosclerosis can be labeled as disease ofconformation. The surplus of palmitic saturated fatty acids in food, phenotype E2/E2 and deletion of gene apoB-100-receptor are causes of intima lesion. The non-ligand lipoproteins form destructive process, dying foam cells and macrophages--inflammatory component. The atheromatosis is a result of realization of biological function of endoecology, support of "purity" of intercellular medium.

[Diagnostic significance of different apolipoprotein levels during hypertriglyceridemia].

Active receptor-mediated uptake of fatty acids (as lipids in VLDLP and LDLP) involves dynamic apolipoproteins apoE and apoC-III. Modern methods allow apoB-100 and apoA-1 to be determined both separately and together in HDLP and VLDLP+LDLP. We estimated diagnostic significance of simultaneous apoE and apoC-III determination in the serum and two LP classes in the patients having either physiological levels of triglycerides or moderate and pronounced hypertriglyceridemia. Serum apoE and apoC-III increased with increasing triglyceride levels and percent of prebeta-LP fractions in electrophoresis. There was significant correlation between apoE and apoC-II content in the sera and in apoB-100 LP. It precludes using measurements of apoproteins for differential assessment of VLDLP and LDLP uptake by the cells or differential diagnostics of primary phenotypes and secondary hyperlipoproteinemias. The apoE content in LDLP was increased only in 1/5 of the patients with marked hyertriglyceridemia. The ApoE an apoC-III content in lipoproteins is of no diagnostic value; it is enough to determine serum apoprotein levels. Significant correlation between HDLP cholesterol and apoA-1 and between LDLP and apoB-100 questions the necessity of measuring serum apoA-1 and apoB.

[Lipoprotein-associated phospholipase A2 in subjects at low and moderate risk estimated by the SCORE scale].

The aim of the work was to elucidate the relationship between PLA2 content and results of the tests of abnormal lipid transfer in lipoproteins (LP) in subjects at low and moderate risk estimated by the SCORE scale. Another aim was to estimate the diagnostic value of plasma PLA2 content that was determined in 378 subjects (285 women and 93 men) aged 30-64 yr at low and moderate risk (SCORE scale). The patients were divided into groups depending on the age, the number of atheroscleroic plaques (ACP) in carotid arteries (0ACP 1 ACP, more than 1 ACP), enhanced and normal PLA2 levels. PLA2 was measured using PLAC Test Elisa Kits (DiaDexus, USA), with the upper normal limit assumed to be 200 ng/ml. In women, PLA2 levels positively correlated with apoA-1 (main HDLP apoprotein) content (r = 0.51, p < 0.03); in men, PLA2 negatively correlated with TG (r = -0.38, p < 0.01); in subjects with homogeneous ACP PLA2 positively correlated with LP(a) (r = -.38, p < 0.03). Simultaneous rise in PLA2 and LP(a) levels may be a significant risk factor of atherosclerosis and atherothromhosis. Enhanced levels of TG, PLA2, and LP(a) may be the biochemical triad of "soft" plaque formation in the intima.

[The hyperuricosuria in patients with high content of triglycerides: the combination of genetic and environmental factors and tactics of treatment].

The increasing of uric acid level (hyperuricosuria) is regularly detected in blood during the examination of patient with such cardiovascular diseases as arterial hypertension, atherosclerosis, diabetes mellitus, metabolic syndrome and obesity. The hyperiricosuria and hypertriglyceridemia are two independent risk factors, especially for arterial hypertension. The higher level of uric acid combined with hyper-lipoproteinemia (phenotypes) IIa and IIb was noted in 65% of patients. In males, hyperiricosuria was detected more often than in females. In groups with higher content of uric acid, the significant difference between median and quartiles was determined concerning the indicators of height, body mass, triglycerides concentration, beta-lipoprotein fractions content, pre beta-lipoprotein fractions content, apolipoprotein E in blood serum and apolipoprotein B=100 lipoproteins, but not both apolipoprotein C=III and apolipoprotein E in lipoproteins of high density. The increase of concentration of triglycerides and uric acid in blood is the outcome of disorder of metabolism of fat acids and nucleotides under surplus intake of substances with food. The fructose of sweet drinks can be considered as the source of fructose. The fructose is capable to increase the concentration of uric acid The catabolism of nucleotides is under regulatory impact of fructose: dicarboxylic derivatives can provoke increase of uric acid concentration. The treatment of patients with hyper-triglycerideimia, hyperiricosuria and hyperglycemia has to begin from decreasing of triglycerides concentration, dietotherapy and further if it is necessary, to apply the hypolipidemic therapy with fibrates.

[The secretory phospholipase A2 and transport of lipids by lipoproteins in patients with the risk of cardio-vascular pathology (the system "score") of lower and average degree. The diagnostic significance of the test].

The clinical and pathomorphologic data demonstrate that the most frequent cause of cardiac infarction is the formation of "soft" atheromatosis plaques in the intima of arteries. Their rupture results in thrombosis of coronary arteries. The plaques are characterized by higher content of triglycerides. On the basis of the research data, it is possible to validly consider that the detection of secretary phospholipase content A2 conjugated with lipoproteins is the test of systemic inflammatory response. This response is formed under atherosclerosis in vivo as a feedback to the accumulation in the intercellular medium of the endogenic flogogens (initiators of biological reaction of inflammation)--lipoproteins of lower density subclass A. Their utilization in the intima, as a pool of local interstitial tissue, by the resident macrophagocytes transformed from monocytes result in the formation of doth soft and disposed to laceration atheromatosis plaques and the atherothrombosis of coronary arteries and rarer of carotids. Concurrently, the increase of lipoproteins content in blood plasma is supposed to be the test of proliferation of cells in vivo, the smooth muscle cells of medium in particular. The simultaneous detection of content of secretory associated with lipoproteins phospholipase A2 and lipoprotein (a) can be considered as a valid risk factor of atherosclerosis and atherothrombosis--atheromatosis of intima of arteries with the formation of "soft" plaques in the intima, their laceration and thrombosis of coronary arteries and clinical presentation of cardiac infarction. The diagnostic triad of formation of soft plaques in the intima can be composed of the higher level of triglycerides, the content of protein of phospholipase A2 and lipoprotein (a).

[Lipid blood spectrum in patients with amiodarone associated hypothyroidism. Effect of replacement therapy with L-thyroxine].

Blood lipid levels were measured in 23 patients with amiodarone associated hypothyroidism (most of them had ischemic heart disease). Abnormalities of lipid spectrum were found in 12 of these patients. All 12 patients were subjected to replacement therapy with l-thyroxine. Compensation of thyroid status was associated with average 12.6 and 12.3% lowering of total and low density lipoprotein cholesterol, respectively. However target levels of low density lipoprotein cholesterol were achieved only in 1 patient. There were no significant changes of high density lipoprotein cholesterol and triglycerides.

[Co-renitek treatment of patients with moderate and severe forms of hypertensive disease]. / Ko-renitek pri lechenii bol'nykh s umerennoi i tiazheloi formami gipertonicheskoi bolezni.

AIM: To evaluate efficacy and tolerance of a compound drug co-renitec combining an ACE inhibitor enalapril maleate and diuretic hydrochlorothiazide co-renitec taken for 16 weeks in essential hypertension (EH). MATERIAL AND METHODS: 28 patients with EH (16 males and 12 females aged 47-74 years) of mean duration 13.1 +/- 1.6 years. Blood pressure (BP) was monitored for 24 hours with the device SL 90207 (SpaceLabs Medical, USA). Microalbuminuria (MAU) was estimated with the use of immunoturbodimetric test. RESULTS: By 24-hour monitoring, co-renitec reduced day BP by 14.9/8.9 +/- 3/2 mm Hg, nocturnal BP lowered by 18.6/11.4 +/- 3/2 mmHg, pulse pressure also fell. Coefficient T/P was 53.5% for systolic BP (SBP) and 59.6% for diastolic BP (DBP). The target SBP was reached in 77% patients, target DBP--in 69%. Co-renitec significantly decreased MAU, albumines excretion normalized in 46% patients. CONCLUSION: Co-renitec lowers both day and nocturnal blood pressure, improves 24-h rhythm of BP, has a positive effect on the kidneys. This allows its recommendation as a first-line drug in patients with moderate and severe EH.

Intensification of free radical oxidation of low-density lipoproteins in the plasma of patients with ischemic heart disease receiving beta-hydroxy-beta-methylglutaryl-coenzyme A reductase inhibitor cerivastatin and inhibition of low-density lipoprotein peroxidation with antioxidant probucol.

Inhibitors of the key enzyme of cholesterol biosynthesis beta-hydroxy-beta-methylglutaryl-coenzyme A reductase (statins) decrease cholesterol content in atherogenic low-density lipoproteins in patients with coronary heart disease and hypercholesterolemia, but inhibited biosynthesis of ubiquinone Q10 protecting low-density lipoproteins from free radical oxidation. Cerivastatin in a daily dose of 0.4 mg markedly increased the content of lipid peroxides in low-density lipoproteins. However, complex therapy with cerivastatin and antioxidant probucol (250 mg/day) was accompanied by a sharp decrease in the content of lipid peroxides in low-density lipoproteins in patients with coronary heart disease in vivo. These data indicate that antioxidant agents should be used in combination with inhibitors of beta-hydroxy-beta-methylglutaryl-coenzyme A reductase (hypolipidemic preparations) for the therapy of patients with coronary heart disease.