[Lipolysis in very low density lipoproteins - locus minoris resistentiae - in the pathogenesis of hypertriglyceridemia. Positive effects of diet, polyenic fatty acids, statins and fibrates.]

Inhibition of hydrolysis of palmitic and oleic triglycedires (TG) in very low density lipoproteins (VLDL), slow formation of active apoВ-100 conformation, blockade of апоЕ/В-100 ligand formation in VLDL and their reduced uptake by insulin-dependent cells cause hypertriglyceridemia (HTG). Palmitic and oleic VLDL (>80% total VLDL) are not converted in low density lipoproteins (LDL). Atherosclerosis is not an alimentary deficiency of polyenic fatty acids (PFA), but results from low in vivo bioavailability of PFA in LDL against the background of high dietary palmitic FA and palmitic LDL. Plasma PFA content and cellular PFA deficiency are as high as LDL cholesterol (CL). Primary prevention of atherosclerosis should be based on a decrease in dietary content of palmitic saturated FA, trans FA and a moderate increase in PFA. It seems highly unlikely that the xeobiotics statins, fibrates and probucol produce pleiotropic biological effects in vivo. These effects are brought about by phylogenetically early humoral mediators eicosanoids: prostacyclins, prostaglandins, thromboxanes, leukotrienes, and resolvins. It is reasonable to suggest that all preparations which act according to the same algorithm activate TG hydrolysis in VLDL and normalize cellular uptake of PFA in linoleic and linolenic LDL via apoВ-100 endocytosis. Atherosclerosis is a syndrome of cellular deficiency of essential polyenic FA.

[Clinical biochemistry methods in objectiva evalution of overeating foood of carnivores (meat)by a phylogenetically herbivorous homo sapiens (a patient).]

The abuse of food of carnivores (meat) by phylogeneticallyI herbivorous Homo sapiens (a patient) initiates atherosclerosis. Addressing biogenetic law of E. Haeckel that ontogeny recapitulates phylogeny (a universal anamnesis), we suggest a diagnostic technique that allows evaluation of the meat diet abuse by a herbivorous Homo sapiens. This technique is based on application of phylogenetic theory of general pathology to clinical practice. The degrees of objective evaluation of nonphysiological overeating of meat are: the first, an increase in the fast plasma content of oleic triglycerides palmitoyl-oleyl-palmitate (POP). The second, hyperglyceridemia + an increase in low density lipoprotein cholesterol (LDL-CL) content. The third, increased plasma content of apoС-III. The fourth, an increase in the concentration of apoВ-48. If electrophoregrams are analyzed and hyperlipoproteinemia (HLP) type is determined according to WHO classification, the first degree of meat overeating is not informative, the second, corresponds to type IV HLP; the third, to type IIb HLP, and the forth, to type V HLP, i.e, the patient diet consists practically of the food of carnivores. Hyperlipoproteinemia coincides with insulin resistance syndrome, hyperglycemia and hyperinsulinemia, which is based on blood increase of fatty acids in the form of polar unesterified fatty acids (UFA). According to phylogenetic theory of general pathology, in vivo cells do not internalize glucose if there is a possibility to internalize UFA. Preventive examination allows evaluation of disorders in the biological function of trophology (food consumption). Thus, the use of different methods in the analysis of this function offers evaluation of the effectiveness of diet therapy from the level of disorders when treatment was started.

[The becoming of reactions of lipolysis in phylogenesis. The palmitic and oleic triglycerides as substrates. Insulin, condition of normolipemia and formation of hyper lipoproteinemia type IIb, IV and V].

According to phylogenetic theory of general pathology, when living in ocean all were carnivorous (piscivorous) fatty acids transferring to cells in form of non-polar triglycerides nitially began apoB-48 chylomicrons, continued lipoproteins of very low and low density and fnalized its apoB-100 endocytosis. The fatty acids are transferred by chylomicrons + lipoproteins of very low density + lipoproteins of low density and non-polar triglycerides are hydrolyzed by hepatic glycerolhydrogenase and co-enzyme apoC-III; according WHO classifcation, hyperlipoproteinemia corresponds to type V. On land, in herbivorous who are not yet synthesized insulin, apoB-48 and chylomicrons left process of non-polar triglycerides transferring. In lipoproteins of very low density and lipoproteins of low density, the carnivorous transfer exogenous palmitic non-polar triglycerides. The herbivorous also transfer palmitic non-polar triglycerides though synthesized by hepatocytes from glucose endogenically. In herbivorous, transferring of palmitic non-polar triglycerides prior to synthesis of insulin is forming apoB-100 in composition of lipoproteins of very low density and lipoproteins of low density. The hydrolysis of palmitic non-polar triglycerides in lipoproteins of very low density is activated by hepatic glycerol hydrogenase and apoC-III; cells absorb lipoproteins of low density by means of apoB-100 endocytosis. The content on lipoproteins in blood plasma under electrophoresis of lipoproteins corresponds to hepatic glycerol hydrogenase type IIb. In frst and second types of fatty acids transferring in form of triglycerides to lipoproteins of very low density + lipoproteins of low density predominate palmitic fatty acid, triglycerides of the same name and palmitic metabolism of fatty acids in vivo. The insulin initiated the third type of transferring of oleic fatty acid by now to insulin-depended cells only in oleic lipoproteins of very low density; hydrolysis of oleic triglycerides is activated by late in phylogenesis post-heparin hepatic glycerol hydrogenase and apoC-II cofactor. The dynamic apoE is actively bound by apoB-100 forming apoE/B-100 ligand. At later stages of phylogenesis insulin formed fatty acids transferring in form of oleic triglycerides in lipoproteins of very low density of the same name without forming of oleic lipoproteins of low density; the electrophoregram of lipoproteins reflects absence of hepatic glycerol hydrogenase. In phylogenesis three types of fatty acids transferring to triglycerides in composition of lipoproteins formed sequentially: 1) chylomicrons + lipoproteins of very low and density + lipoproteins of low density; 2) lipoproteins of very low density + lipoproteins of low density; 3) only in lipoproteins of very low density. The frst one is specifc to piscivorous (carnivorous) while living in ocean. The second one is implemented by herbivorous while they didn't begin to synthesize insulin and hepatocytes not yet transform all endogenous palmitic fatty acid into oleic fatty acid. Insulin initiated: a) transferring of oleic fatty acids to lipoproteins of very low density without forming oleic lipoproteins of low density; b) highly effective oleic metabolism of fatty acids in vivo: c) becoming of biological function of locomotion. The aphysiological induction by substrate, surplus of palmitic fatty acids in food initiate negative alterations in composition of lipoproteins in opposite direction than in case of phylogenesis. When homo sapiens, herbivorous in phylogenesis, begins to misuse carnivorous (meat) food then instead of normolipoproteinemia in blood plasma under electrophoresis of lipoproteins one can initially detect transitory hyperlipoproteinemia type IV and then prolonged hyperlipoproteinemia type IIb. If patient factually passes on to carnivorous diet then hyperlipoproteinemia type V is developing. If content of exogenous palmitic fatty acid in food surpasses physiological capacities of its transferring in oleic triglycerides as palmitoyl-oleyl-palmitate glycerol, palmitic triglycerides as oleyl-palmitoyl-palmitate glycerol begin to form and epigenetically aphysiological non-ligand palmitic lipoproteins of very low density → lipoproteins of low density are formed. Their circulation in blood is a cause of hypertriglyceridemia, higher level of cholesterol-lipoproteins of low density, compensatory increasing of apoC-III. Then occurs induced by substrate formation of hyperlipoproteinemia initially of type IV, then of type IIb and fnally of type V. The pathogenesis of atherosclerosis and atheromotosis is activated when homo sapiens, herbivorous in phylogenesis, begin to misuse carnivorous food affecting biological functions of trophology, reaction of exotrophy (external nutrition), function of homeostasis, endoecology and function of adaptation. The formation of palmitic metabolism if fatty acids instead of oleic one is a cause of chronic defciency of energy and ATP synthesis in vivo. Insulin activates absorption of glucose by cells with purpose to use it for synthesis of oleic fatty acids. In the frst place, insulin regulates in vivo metabolism of fatty acids and only in second place metabolism of glucose.

[Clinical biochemistry methods in objectiva evalution of overeating foood of carnivores (meat) by a phylogenetically herbivorous homo sapiens (a patient).]

The abuse of food of carnivores (meat) by phylogeneticallyI herbivorous Homo sapiens (a patient) initiates atherosclerosis. Addressing biogenetic law of E. Haeckel that ontogeny recapitulates phylogeny (a universal anamnesis), we suggest a diagnostic technique that allows evaluation of the meat diet abuse by a herbivorous Homo sapiens. This technique is based on application of phylogenetic theory of general pathology to clinical practice. The degrees of objective evaluation of nonphysiological overeating of meat are: the first, an increase in the fast plasma content of oleic triglycerides palmitoyl-oleyl-palmitate (POP). The second, hyperglyceridemia + an increase in low density lipoprotein cholesterol (LDL-CL) content. The third, increased plasma content of apoС-III. The fourth, an increase in the concentration of apoВ-48. If electrophoregrams are analyzed and hyperlipoproteinemia (HLP) type is determined according to WHO classification, the first degree of meat overeating is not informative, the second, corresponds to type IV HLP; the third, to type IIb HLP, and the forth, to type V HLP, i.e, the patient diet consists practically of the food of carnivores. Hyperlipoproteinemia coincides with insulin resistance yndrome, hyperglycemia and hyperinsulinemia, which is based on blood increase of fatty acids in the form of polar unesterified fatty acids (UFA). According to phylogenetic theory of general pathology, in vivo cells do not internalize glucose if there is a possibility to internalize UFA. Preventive examination allows evaluation of disorders in the biological function of trophology (food consumption). Thus, the use of different methods in the analysis of this function offers evaluation of the effectiveness of diet therapy from the level of disorders when treatment was started.

[The effect of ABCA1 rs2230806 common gene variant on plasma lipid levels in patients with dyslipidemia.]

The aim of this work was to assess the relationship of rs2230806 SNP of ABCA1 with lipid profile in patients with severe dyslipidemia. The study included 363 patients (42.8% of males), the average age was 48.7 years, 35.5% of patients received hypolipidemic drugs (mainly statins). Quantitative determination of total cholesterol (ТС) and triglycerides (TG) in fasting serum was carried out by a unified enzymatic method, and high density lipoproteins (HDL) - by a direct homogeneous method. Genotype according to the rs2230806 position in the ABCA1 gene was determined by polymerase chain reaction (PCR) «in real time¼ using adjacent samples and melting reaction products after PCR. The frequencies of alleles and genotypes of variant rs2230806 of ABCA1 gene in patients with dyslipidemia did not differ from those in the control group of healthy individuals (athletes). The levels of plasma lipids - TC, TG and HDL cholesterol, on average, in patients with dyslipidemia were 7.8±3,4, 3,4±6,5 and 1.29±0.4 mmol/l, respectively. Compared to different genotypes, the plasma lipid concentrations did not differ significantly, but the analysis of different inheritance models of the allelic variant studied showed a significant association with the level of TG in the additive model, in which each minor allele (a) further enhanced the effect on the level of plasma TG at 1.02 mmol/l (p=0.044). The results of this study demonstrate the effect of a common variant rs2230806 of the ABCA1 gene on the plasma TG level in patients with severe dyslipidemia.

[Atherosclerosis and atheromatosis are consequtive metabolic disordes. Pathology of the biological functions of trophology and endoecology is the basis for ischemic heart disease prevention.]

Atherosclerosis and atheromatosis are different nonphysiological processes with different etiology and pathogenesis. They manifest alterations in different biological functions. According to our original phylogenetic theory of general pathology, atherosclerosis is associated with altered biological function of trophology, eating, biological reaction of exotrophy. Atherosclerosis is induced by eating of nonoptimal for phylogenetically herbivorous Homo sapiens meat diet with high content of palmitic saturated fatty acid (SFA), which leads to in vivo formation of phylogenetically early low-efficient palmitic pathway of FA metabolism instead of highly-efficient oleic pathway operating in herbivores. Accumulation of nonligand palmitic very low density lipoproteins (VLDL) and low density lipoproteins (LDL) in the bloodstream results from nonphysiological reaction of compensation upon transport of palmitic SFA to cells. An increase in blood content of palmitic triglycerides (TG) and nonligand palmitic VLDLЛ→LDL coincides with the development of hypercholesterolemia: type IV→ type IIb → type V. Atheromatosis compensates changes in lipoproteins by activation of the biological function of endoecology (purity of the extracellular medium) in vivo, thus fulfilling the biological reaction of inflammation. This is physiological denaturation of apoВ-100 in nonligand VLDL→LDL by neutrophils via peroxidation, opsonization by the complement components, transcytosis across the endothelial monolayer and removal to the intima of elastic arteries that serves as a collection and utilization pool for phogogens from local intravascular pool of the intercellular medium. Endogenous phlogogens are utilized by phylogenetically early polyfunctional resident macrophages which are small in number and do not proliferate. Blood-borne monocytes-macrophages are also involved in this process, however, they do not express acid hydrolase of polyenic cholesteryl esters. Atheromatous masses are partially catabolized polyenic FA esterified by the alcohol cholesterol which were not internalized by cells. Atheromatosis is a process of pathological compensation in the realization of the function of endoecology. Prevention of atherosclerosis and atheromatosis should be based on elimination of the effects produced by a nonphysiological meat diet.

[The individual fatty acids of blood plasma: biological role of substrates, parameters of quantity and quality, diagnostic of atherosclerosis and atheromotosis.]

The atherosclerosis and atheromotosis are supposed to be, according to phylogenetic theory of general pathology, two etiologically different aphysiological processes, unified by community of pathogenesis. The atherosclerosis is a derangement of biological function of trophology (feeding), biological reaction of exotrophy (external feeding) and biological function of adaptation, biological reaction of compensation in response to deficiency of ῳ-3 and ῳ-6 polyenoic fatty acids. In case of deficiency of polyenoic fatty acids in cells and during synthesis of eicosanoids of group I from unsaturated endogenous ῳ-6 С20: 3 digomo-γ-linoleic unsaturated fatty acid, atherosclerosis is developed, a complex metabolism disorder in vivo. The atheromotosis is a derangement of biological function of endoecology, biological reactions of inflammation and inherent immunity. This incomplete utilization in intima of arteries of non-ligand palmitic lipoproteins of very low → low density under effect not of polyfunctional resident macrophage but monocytes of hematogenic origin without expression of acid hydrolase of polyenoic ethers of cholesterol. In intima, in area of cumulation of endogenous phlogogens (initiator of inflammation) from the pool of intra-vascular medium, polyenoic unsaturated fatty acids are cumulated that were not absorbed by cells in structure of ligand low density palmitic lipoproteins using apoB-100- endocytosis. The pathogenic factor of atherosclerosis - derangement of biological function of trophology. biological function of exotrophy under alimentary deficiency of in vivo of ῳ-3 and ῳ-6 polyenoic fatty acids with physiological parameters of feeding. The pathogenic factor of atheromotosis - phylogenetically herbivorous (carnivorous) human misusing of animal (meat) food, palmitic unsaturated fatty acids, development by hepatocytes of a large number of palmitic triglycerides and lipoproteins of very low density of the same name. The late in phylogenesis insulin-dependent lipoproteins of very low density transfer palmitic lipoproteins of very low density to cells slowly. The cells absorb them also slowly. The cumulation of non-ligand palmitic lipoproteins of very low density → low density in blood competitively blocks physiological absorption of polyenoic unsaturated fatty acids by cells in structure of physiological palmitic lipoproteins of low density. The atherosclerosis occurs blood flow and atheromotosis in intima of arteries of elastic type.

[The atherosclerosis and atheromatosis as two etiologically different aphysiological processes at single pathogenesis. Atheromatosis and pathogenetic role of insulin.]

It is supposed that at stages of phylogenesis seven biological functions was developed: 1) biological function of trophology; 2) homeostasis; 3) endoecology; 4) adaptation; 5) continuation of species; 6) locomotion; 7) cognitive function, including intellect. The function of trophology (feeding) is implemented by two biological reactions: exophilia - external feeding and endophilia - internal feeding. The function of endoecology prevents exceeding of upper limit of physiological interval by no substrate, catabolites and endogenous phlogogens. It is implemented by two biological functions: excretion and inflammation. The etiological factors of atherosclerosis are the following ones. The oleic mono-saturated fatty acid in chemical reactions is by far more active than palmitic fatty acid. In the ocean, all animals were carnivorous (piscivorous); species Homo Sapiens, in millions of years of life on dry land, forcedly became a herbivorousone. The main role in development of herbivorous animals belongs to insulin; the hormone regulating in the first-place metabolism of fatty acids, expresses transmutation of all endogenously synthesized from glucose palmitic saturated fatty acid in oleic monosaturated fatty acid. The late in phylogenesis insulin can't initiate transmutation of exogenous palmitic saturated fatty acid of food into oleic mono-saturated fatty acid. Under effect of insulin in vivo an active oleic type of metabolism of fatty acids is developed; and outside if effect of insulin palmitic type of metabolism of fatty acids is developed. In the ocean, synthesis of active eicosanoids occurs from ῳ-3 polyene fatty acids; there is no such fatty acids in dry land. The basis of pathogenesis of atherosclerosis is feeding of large amount of carnivorous (meat) food by phylogenetically herbivorous Homo Sapiens. This way a deficiency of palmitic saturated fatty acids in cells if developed blocking their bio-accessibility. The lipoproteins of low density are not developed in the initiated by insulin transfer of oleic triglycerides to cells in oleic apoE/B-100 lipoproteins of very low density and their absorption by cells. The transfer of triglycerides into lipoproteins of very low density is blocked under slow processes of transmutation of palmitic lipoproteins of very low density into lipoproteins of low density, retention cumulation of lipoproteins of low density in blood. Only because of partial utilization by monocytes of non-ligand palmitic lipoproteins of very low density →lipoproteins of low density that occurs in the intima of arteries of elastic type, atheromotosis is developed. The atheromotosis masses of intima are first of all interim catabolites of polyene fatty acids; the cells could not to absorb them by apoB-100-endocytosis in the content of lipoproteins of low density. The atherosclerosis, hyperlipoproteinemia, high content of lipoproteins of low density in blood and deficiency of polyene fatty acids in cells are a result of disorder of trophology function; the atheromotosis of arteries is only partial implementation of endoecology function.

[How surplus of palmitic fatty acid in food initiates hypertriglyceridemia, increases cholesterol of low density lipoproteins, triggers atherosclerosis and develops atheromatosis.]

In phylogenesis, the first transfer of all fatty acids to cells is implemented by high density lipoproteins. Later, unsaturated and polyene fatty acids are transferred to cell by low density lipoproteins. The insulin-depended cells absorb palmitic saturated fatty acid, oleic mono-unsaturated fatty acid and of the same name triglycerides in very low density lipoproteins. The hepatocytes secrete palmitic, oleic and linoleic very low density lipoproteins separately. In blood, under hydrolysis of triglycerides, cells absorb ligand palmitic and oleic very low density lipoproteins by force of апоЕ/В-100 endocytosis; they are not transformed into low density lipoproteins. The palmitic saturated fatty acids in the form of polyether of cholesterol turn into linoleic very low density lipoproteins from high density lipoproteins at impact of protein transferring polyene ethers of cholesterol. They transform very low density lipoproteins into low density lipoproteins of the same name; the cells absorb them by force of апоЕ/В-100 endocytosis. In physiological sense, amount of oleic very low density lipoproteins are always more than palmitic of very low density lipoproteins. Under syndrome of insulin-resistance there is no transformation of palmitic saturated fatty acid synthesized from glucose in vivo into oleic mono-saturated fatty acid. The hepatocytes secrete into blood mainly palmitic very low density lipoproteins which amount exceeds oleic very low density lipoproteins. Under slow hydrolysis in blood, main mass of palmitic very low density lipoproteins becomes palmitic low density lipoproteins. These very lipoproteins initiate hyperlipidemia, increase content of cholesterol of cholesterol-low density lipoproteins, lower cholesterol-high density lipoproteins, decrease bio-availability of polyene fatty acids for cells, trigger development of atherosclerosis and formation of atheromatosis in intima of arteries. The aphysiologic effect of surplus of palmitic saturated fatty acid in vivo and triglycerides of the same name can't be eliminated under increasing of content of ω-3 polyene fatty acids in food and effect of statines. All this is to be rationally applied in prevention of hypertriglyceridemia, atherosclerosis, atheromatosis of coronary arteries, ischemic heart disease and myocardium infarction.

[The disturbance of unification of coupled biochemical reactions in synthesis of endogenous ω-9 oleic acid. The resistance to insulin, stearic triglycerides and pathogenesis of eruptive xanthomata].

The eruptive xanthomata are formed in vivo under realization of biological function of endoecology. The xanthomata are formed in tissues by early in phylogenesis resident macrophages at absorption of secreted by hepatocytes aphysiological stearic lipoproteins of very low density with high content of the same name triglycerides down to tristearate. In these lipoproteins of very low density, by force of aphysiologically high hydrophobicity, stearic triglycerides are not hydrolyzed by post-heparin lipoproteinlipase. They both do not associate apoE and form apoE/B-J00 ligands. The formation of stearic lipoproteins of very low density occurred at impairment of function of coupled biochemical reactions in synthesis of physiological ω-9 oleic mono unsaturated fatty acid in hepatocytes. To synthesize endogenous oleic mono unsaturated fatty acid the late in phylogenesis insulin expresses two enzymes of coupled biochemical reactions: palmitoyl-KoA-elongase andstearyl-KoA-desaturase, activating synthesis of fatty acids following the path glucose-endogenous palmitic unsaturated fatty acid-stearic unsaturated fatty acid-oleic mono unsaturated fatty acid. The uncoupling of enzymes of coupling synthesis forms in hepatocytes surplus of stearic mono unsaturated fatty acid, stearic triglycerides and of the same name aphysiologic lipoproteins of very low density. During inhibition of the second enzyme the first one continues to actively produce stearic unsaturated fatty acid which the second enzyme, already uncoupled, does not convert into oleic unsaturated fatty acid. By absorbing aphysiologic ligand-free stearic lipoproteins of very low density in biologic reaction of endoecology, phylogenetically early macrophages convert into foam cells initiating aphysiologic biological reaction of transcytosis, biologic reaction of inflammation, biologic reaction of apoptosis and formation of eruptive xanthomata. The lipids of eruptive xanthomata: such endogenous stearic triglycerides as tristearate, tripalmitate, exogenous carotenoids, phospholipids and unesterified cholesterol.

[Atheromatosis of arterial intima].

Phylogenetically late arterial intima of the elastic type contains no proteins for the transfer of ligandless oxidized low density lipoproteins (LDLP) for sedentary macrophages adsorbed on the matrix. Phylogenetically early cells realize the extracellular digestive reaction by releasing proteolytic enzymes (metalloproteinases) into intimal matrix that hydrolize matrix proteoglycans, adsorbed ligandless LDLP, detritus, and complete lysosomal hydrolysis of the most hydrophobic polyenic cholesterol esters (poly-ECS). Smooth muscle cells migrate from the middle muscular layer of the arterial wall, change their contractile phenotype to secretory one, and synthesize in situ de novomatrix proteoglycans. The arterial wall has three layers (monolayer endothelium, intimal media (smooth muscle cells), and adventitia) only in elastic type arteries. It is desirable to elucidate functional differences between phylogenetically early sedentarymacrophages and monocytes-macrophages of later origin and understand whether theydepends on specific features of activity of scavenger eceptors, CD36 translocases, expression of acid hydrolases synthesis for poly-ECS or realization of the extracellular digestion reaction. We believe that formation of atheromatous masses takes place in the matrix of arterial intima rather than in lysosomes taking into account limited possibilities for monocytes-macrophages to realize endocytosis of ligandless LDLP from the matrix. Given that atheromatosis is a syndrome of deficit of essential polyenic fatty acids (PFA) in the cells, intimal atheromatosisshould be regarded only as partial utilization of excess PFA in the matrix of elastic type arteries. At later stages of phylogenesis, intima was formed from media smooth muscle cells.

[Consecutive formation of the functions of high-, low-density and very-low-density lipoproteins during phylogenesis. Unique algorithm of the effects of lipid-lowering drugs].

During phylogenesis, all fatty acids (FA) were initially transported to cells by apoA-I high-density lipoproteins (HDL) in polar lipids. Later, active cellular uptake of saturated, monoenoic and unsaturated FA occurred via triglycerides (TG) in low-density lipoproteins (LDL). Active uptake of polyenoic FA (PUFA) required the following: a) PUFA re-esterified from polar phospholipids into nonpolar cholesteryl polyesters (poly-CLE), b) a novel protein, cholesteryl ester transfer protein (CETP), initiated poly-CLE transformation from HDL to LDL. CETP formed blood HDL-CETP-LDL complexes in which poly-CLE spontaneously came from polar lipids of TG in HDL to nonpolar TG in LDL. Then ligand LDLs formed and the cells actively absorbed PUFA via apoB-100 endocytosis. Some animal species (rats, mice, dogs) developed a spontaneous CETP-minus mutation followed by population death from atherosclerosis. However, there was another active CETP-independent uptake formed during phylogenesis; the cells internalized poly-CLE in HDL. Since apoA-I had no domain-ligand, another apoE/A-I ligand formed; the cells began synthesizing apoE/A-1 receptors. In cells of rabbits and primates absorbed cells PUFA consecutively: HDL-->LDL-->apoB-100 endocytosis; those of rats and dogs did HDL directly: HDL-->anoE/A-I endocytosis. In the rabbits, CETP was high, apoE in HDL was low, and the animals were sensitive to exogenous hypercholesterolemia. In the rats, CETP was low and ApoE in HDL-was high, and the animals were resistant to hypercholesterolemia. Reduced bioavailability of PUFA during their consecutive cellular uptake and develdpment of intercellular PUFA deficiency are fundamental to the pathogenesis of atherosclerosis.

[The contamination under polymerase chain reaction studies: problems and solutions].

The study was carried out to determine risk factors of false positive and false negative results under polymerase chain reaction-analysis of clinical material. The samples with high viral load can be the source of false positive results. The contamination with nucleic acids can occur at any section of polymerase chain reaction analysis. The study data permitted to establish that the most sensitive stage is isolation and purification of nucleic acids especially under manual mode of operation. The detection of positive signal in most samples of one setting indicates total contamination. The cases when only several samples are polluted are special challenge. The presence of sample with high concentration of viral nucleic acid and several samples with low concentration in one setting means necessity of repeated analysis beginning with stage of isolation of nucleic acid. The analysis of curves of accumulation of products of amplification, their forms and positioning on chart is the obligatory stage of polymerase chain reaction study in real time regimen. These actions permit to exclude the readouts of false negative testing results to departments. The study conclusions are equipotent for polymerase chain reaction testing of any nucleic acid targets.

[THE LIPOLYSIS IN PHYLOGENETICALLY EARLY LIPOPROTEINS OF LOW DENSITY AND MORE LATER LIPOPROTEINS OF VERY LOW DENSITY: FUNCTION AND DIAGNOSTIC VALUE OF APOE AND APOC-III].

According to phylogenetic theory of general pathology, the function of low density lipoproteins (LDL) and hydrolysis of triglycerides (TG) in them under the effect of hepatic glycerol hydrolase apoC-III (HGH) developed at much earlier stages of phylogenesis than functioning of insulin-dependent phylogenetically late very low density lipoproteins (VLDL). For millions ofyears, lipolysis and HGH+apoC-III have activated transfer of polyenic fatty acids (FA) in the form of cholesteryl polyesters (CLE) from high density lipoproteins (HDL) to linoleic and linolenic LDL under the effect of cholesteryl ester transfer protein. It is reasonable to suggest that hepatocytes physiologically secrete oleic and palmitic VLDL and linoleic and linolenic LDL. Cells uptake ligand oleic and palmitic VLVL by apoE/B-100 receptor-mediated endocytosis. Physiologically, VLDL are not converted to LDL. If hepatocytes secrete palmitic VLDL in greater amounts than oleic VLDL upon slow hydrolysis ofpalmitic TG and under the effect of postheparinic lipoprotein lipase+apoC-II, only some proportion of palmitic TG is uptaken by cells as VLDL, and the rest is converted in ligand-free palmitic LDL These LDL increase plasma contents of TG and LDL-cholesterol and form small dense palmitic LDL. Expression of HGH+apoC-III synthesis compensates TG hydrolysis in nonphysiological palmitic LDL. In vivo, apoC-III is neither physiological no pathological inhibitor of lipolysis. Increase in plasma apoC-III content is an indicator of accumulation of non-physiological palmitic LDL and atherosclerosis-atheromatosis risk factor ApoE content ofpalmitic LDL increases together with apoC-III, i.e., apoE in ligand VLDL is not internalized via apoE/B-100 endocytosis. An increase in apoC-III and apoE contents are reliable in vivo tests for the rise inpalmitic FA, palmitic TG and excessive secretion of palmitic VLDL by hepatocytes. ApoC-III and apoE contents in LDL are additional tests to evaluate the efficiency of atherosclerosis prevention when physiological function of trophology and biological reaction of exotrophy are normalized.

[The clinical biochemistry of hyperlipemia and hyperglycemia. Insulin and metabolism of fatty acids. Hypoglycemic effect of hyperlipemicpharmaceuticals].

The regulation of metabolism of glucose is billions years older than system of insulin and biological function of locomotion (function of motion). Hence hypoglycemic effect of hormone is mediated by alteration of metabolism of fatty acids. The insulin in physiological way deprives mitochondrions a possibility to metabolize ketone bodies, short chain, medium chain and long chain fatty acids and 'forces" them to oxidize glucose which phylogenetically is not an optimal substrate. The relationships between fatty acids and glucose in the Rendle cycle have an effect only on autocrine level (in cell) determining alternation of biological reactions of exotrophia (after food intake) and endotrophia (beyond food intake) in biological function of alimentation (trophology). The most anti-diabetic pharmaceuticals are as insulin hyperlipemic by their mechanism of action. The decrease content of lipid substrates of oxidation in cytosol of cells and mitochondrions "are forced" to oxidize glucose. In these conditions, insulin enhances absorption of glucose by cells through glucose carriers--GLUT4. The derivatives of sulfonil-urea increase secretion of insulin by beta-cells of islets. The biguanidines bond in cytosol covalently and irreversibly ketone bodies taking them away from oxidation in mitochondrions. The fibrates, glitazones, flavonoids and flavones, lipoic tio-fatty acids. The endogenous eicosanoids, derivatives omega-3 and omega-6 of essential polyolefinic fatty acids and conjugated unsaturated fatty acids are the antagonists of receptors of activation of proliferation of peroxisomes. In peroxisomes, they enhance alpha-, beta- and omega-oxidation of all exogenous a physiological fatty acids and excess of palmitic saturated fatty acid forming hypolipidemia in cytozol. The hypolipidemic pharmaceuticals with effect of beta-blocker of oxidation stop absorption of fatty acids by mitochondrions. The omega-3 essential polvolefinic fatty acids, simultaneously with hypolipidemic effect, activate function of GLUT4. In patients of middle age, the diabetes mellitus type II is a symptom of syndrome of atherosclerosis. The reason is that in cells the deficiency of essential polyolefinic fatty acids and is determined by derangement of synthesis of phospholipids and function of GLUT4. It is valid to consider diabetes mellitus primarily as a pathology of metabolism of fatty acids and secondly as a pathology of content of glucose. It is necessary to take into account both under treatment (tactic activities) and strategic program of prevention of diabetes mellitus in population.

[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.

[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.

[Clinical and laboratory detection of phenotypic characteristics in patients with high hypertriglyceridemia].

The purpose of the study was to define the values of clinical and biochemical (phenotypic) differences in 2 groups of patients: 1) those with moderate (< or =4.5 mmol/l) blood triglyceride (TG) levels and 2) those with high (more than 4.5 mmol/l) blood TG levels and to reveal significant parameters of a diagnostic algorithm for primary and secondary forms of hypertriglyceridemia (HTG). Ninety-six (54%) patients females) with a TG level of more than 2.3 mmol/l were examined. The age was 12 to 71 years (median [quartiles] 50 years [41-61 years]); women accounted for 54%. The patients had the following diseases: coronary heart disease (CHD) (44.89%), myocardial infarction (13.5%), arterial hypertension (87.9%). The diagnosis of HTG included an algorithm for the clinical, biochemical, and clinicogenealogical examination of patients. Biochemical blood analysis involved lipoprotein parameters: cholesterol, triglycerides, low-density lipoprotein cholesterol, lipid electrophoresis, apolipoproteins Al, B-100, E, and C-III. The data were processed using the statistical packages STATISTICA 6.0 and SPSS 17.0. Comparison revealed no age- and gender-related differences in the parameters between Groups 1 and 2 There was a significant correlation between the high levels of TG and the following indicators: total cholesterol, chylomicrones, lipoprotein(a), LP-E , LP B:E, LP C-III4, and LP C-III, smoking (a risk factor) and with the indicators of other metabolic disturbances--total C, chylomicrones, lipoprotein(a), LP-E-total, LP B:E, LP-C3-total, and LP-C3, which determined the impact of nutrition had a hereditary predisposition through the polygenic mechanisms of gene expression under the influence of a number of factors. Pancreatitis was found to be implicated in the development of HTG. Higher TG levels correlated with the parameters, the diagnosis of which reveals additional metabolic disturbances via environmental and polygenic mechanisms