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Biomedical subjects

V N Titov

Publications and source records attributed to V N Titov.

At least 91 records · Page 5Linked to original sources
PubMed1998

[Determination of lipid composition of high density lipoproteins by thin-layer chromatography on silica gel].

Unidimensional chromatography in a thin layer of silica gel with two solvent systems for separation of the lipid extract of high density lipoproteins (HDLP) detected 10 lipid fractions in subjects with normal lipidemia. Four phospholipid fractions were identified: three main (phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin) and one minor, phosphatidylethanolamine. HDLP lipids include free cholesterol and its esters; three glyceride fractions are detected: mono- di, and triglycerides, and free fatty acids. The ratio of individual phospholipid fractions and of free to ester-bound cholesterol in HDLP determined by computer-aided densitometry of chromatograms coincides with the data obtained routinely. Such a method for assessing the HDLP lipid composition is useful in studies of HDLP in patients with disorders of HDLP metabolism and for assessing the changes in HDLP composition during hypolipidemic therapy.

Cholesterol↗
PubMed1998

[Lipoproteins as a specific circulatory transport system].

In accordance with the systemic approach, each circulatory transport system is highly specific and transports an elementary substance from cell to cell in the hydrated medium. In the author's opinion, the lipoprotein system has also a functional specificity and carries the elementary substance fatty acid in the blood stream. A great variety of fatty acids, the individuality of their physicochemical properties, great stereochemic differences of saturated and polyenic fatty acids make their transport virtually impossible. The steric individuality of fatty acids can be reduced if the acids are covalently bonded by a matrix as complex lipids. For formation of complex lipids, nature prefers esterification of fatty acids with alcohols which have a varying hydrophoby, such as glycerol, sphingosine, cholesterol, cetyl alcohol. The steric differences of saturated and polyenic fatty acids form a basis for their being structurized in different lipids. Triacyl glycerides are a transport form of saturated, monounsaturated fatty acids and their transforms and give rise to a crystalline phase. Phospholipids and cholesterol esters are a transport form of mainly polyunsaturated fatty acids in the polar phase in the former case and in the crystalline phase in the latter one. The individual apolipoproteins structure complex lipids into individual lipoprotein particles and transport them in the hydrated medium of blood flow. Saturated fatty acids chiefly transport lipoprotein particles formed by apoB-48- and apoB-100-isoproteins. Polyenic acids transport mainly high-density apoA-1-lipoprotein particles, which makes up a main physiological function of the latter. Cholesterol is nothing more than a matrix; it reesterifies polyenic fatty acids from the polar transport form of phospholipids into the unpolar transport form of cholesterol esters. Cholesterol esterification of polyenic fatty acids may structure complex lipid in the unpolar phase and transport it to the cells via apoB-100-ligand-receptor interaction, which is considered to be a key stage in the multistage process of active transport to the cells of polyenic fatty acids. However, the significant differences of active and inactive transport of polyenic fatty acids in the blood stream await a separate consideration.

Biological Transport, Active↗
PubMed1998

[A comparison of the hypolipidemic action of probucol at doses of 500 and 1000 mg/day in moderate hyperlipoproteinemia].

AIM: Evaluation of effectiveness of hypolipidemic action of probucol in doses 500 and 1000 mg/day and comparison of probucol blood concentrations on the treatment month 3 and 6. MATERIALS AND METHODS: Probucol (Akrikhin, Russia) was given to 41 patients with primary hypercholesterolemia in a dose 500 mg/day. 3 months later the patients were divided into two groups. Group 1 patients exhibited a > 10% decrease in cholesterol levels and continued to take probucol in the dose 500 mg/day. Group 2 patients were crossed over to higher cholesterol dose--up to 1000 mg/day. Lipids levels were measured by enzyme tests, apoproteins--by immunoturbidimetry and immunodiffusion, probucol concentrations--by high-performance liquid chromatography. RESULTS: After 3 months of treatment, cholesterol lowered by 14.3 and 9.2% in groups 1 and 2, respectively. After 6 months, by 19.7 and 12.9%, respectively. Probucol concentrations in blood were higher after 6 months of treatment than after 3 months in both groups. No significant differences existed between the groups by probucol concentrations in 3 and 6 months. CONCLUSION: Hypolipidemic effect of probucol depended on the individual features of lipoproteins metabolic disorders rather than the drug blood concentration. Larger probucol doses fail to reduce cholesterol further.

Adult↗
PubMed1997

Structure of apo A-I high-density lipoproteins: a review.

Current models of high-density lipoprotein (LP) are reviewed on the basis of physicochemical protein-lipid interactions. The micellar model of LP fails to explain the transformation of micelles into disk-shaped particles and gives an indefinite number of apo A-I molecules in the surface monolayer. Micellar structure fails to explain how changes in the conformation of apoprotein affect the structure and function of high-density LP. The phospholipid bilayer encircled by apoprotein model does not explain the accepting of nonpolar cholesterol esters by high-density LP. The transformation of a bilayer phospholipid disk into a spherical structure is unclear. Since the structure and function of LP are determined by their protein chemistry, an alternative model of high-density LP as a protein-lipid disk is developed. Apo A-I bound with polar phospholipids forms a planar amphipathic disk. Phospholipids containing the more hydrophobic polyene acids are structured by apo A-I in the monolayer on the hydrophobic side of the disk. The less unsaturated polyene acids are structured by apo A-I in the multi-lamellar phase of phospholipid bilayers on the hydrophilic side of the disk. The lateral surface of the disk is formed by hydrophilic domains of apo A-I. Each apo A-I molecule forms a separate LP. Polyene fatty acids are esterified with cholesterol by lecithin-cholesterol acyltransferase on the hydrophobic side of the disk. The cholesterol-esterified polyene acids are accepted here also in association with hydrophobic groups of amino acid residues of apo A-I. Interaction with nonpolar cholesterol esters changes the conformation of apo A-I, forming a cylindrical structure from the planar protein-lipid disk. The lateral surface of the cylinder is formed by the same hydrophilic domains of apo A-I as in the disk-shaped particle. However, the alpha-helices of these domains are arranged perpendicularly to the acyl chains of the phospholipids in the disk but in parallel in the cylinder. The interaction of apo A-I protein-lipid disks by loop domains on the lateral surfaces results in the formation of large disk-shaped structures which are specific for a low-activity lecithin-cholesterol acyltransferase. The interaction of loop domains of cylindrical high-density LP produces hexagonal structures. The heterogeneity of apo A-I LP is caused by the conformation of the apoprotein which depends on the medium: the native conformation in the hydrated medium, the intermediate conformation in association with polar phospholipids, and the final conformation in association with phospholipids and nonpolar cholesterol esters. Functional features of LP depend on the conformation of apo A-I. The active and passive transport of polyene fatty acids to cells is based on the accumulation of phospholipids of different hydrophobicity on the appropriate sides of the apo A-I amphipathic disk.

Apolipoprotein A-I↗
PubMed1997

[Total and lipid-bound sialic acids in the blood in primary and secondary hyperlipoproteinemias].

Total and lipid-bound sialic acids (TSA and LBSA) were measured in the blood of 219 patients with primary or secondary hyperlipoproteinemia (129 patients with ischemic heart disease and 66 patients with diabetes mellitus type II) versus 24 normolipidemic healthy subjects. TSA levels in IHD patients differed significantly from those in IHD-free and diabetic patients. LBSA quantities were the same in IHD and IHD-free patients, being significantly higher in diabetes mellitus than in IHD. These findings give no proves to diagnostic value of TSA and LBSA as markers of IHD and coronary atherosclerosis. TSA levels may be used in the test for disturbed lipoprotein metabolism.

Adult↗
PubMed1997

[Diagnostic significance of glycolipid sialic acids in hyperlipoproteinemias].

Total and lipid-bound sialic acids in the blood were measured and lipoprotein metabolism assessed in 219 men and women with primary (n = 129, coronary patients) and secondary (n = 66, patients with type II diabetes) hyperlipoproteinemias and normolipidemia (n = 24, normal subjects). The level of total sialic acids in coronary patients reliably differed from that in normal subjects or diabetics. The level of lipid-bound sialic acids was the same in coronary patients and normal subjects and reliably higher in diabetics. The results do not confirm the hypothesis about the probable diagnostic value of total and lipid-bound sialic acids as markers of coronary disease and coronary atherosclerosis. Measurement of total sialic acids may be one of the tests verifying the disorders of lipoprotein metabolism.

Adult↗
PubMed1997

[Apolipoprotein E and activity of cholesterol esters transport in type IIA and IIB hyperlipoproteinemia].

The authors studied the activity of cholesterol esters transport (CET), concentrations of apolipoprotein E in the blood and high density lipoproteins (HDLP) in parallel with other parameters of lipoprotein metabolism in 79 males and 62 females. 122 of them had ischemic heart disease (IHD) and primary hyperlipoproteinemia (HLP). 19 healthy controls were normolipidemic. Activation of CET and relative lowering of apoE content in HDLP with relevant increase in lipoproteins containing apoB were seen only in type IIB HLP. CET activity in controls was related to a significant positive correlation with concentrations of both cholesterol (CS) and CS esters (CSE) in HDLP and HDLP3 and negative correlation with the proportion free CS/CSE in HDLP. Opposite to normolipidemic subjects, in type IIB HLP there was a negative relationship between CET activity and HDLP3 CS level and positive--between free CS/CSE in HDLP but not with concentration of CSE and total CS in HDLP. In type IIA HLP patients no relationships were registered between CET activity and HDLP content of total CS and CSE as well as with HDLP3 CS level. In type IIB HLP a significant correlation was found between level of HDLP CS and CET activity. Concentration of apoE in HDLP correlated with apoB level in the serum but not with quantity of HDLP CS. Patients with type IIA HLP exhibited a significant negative correlation between CET activity and HDLP apoE. These patients had no dependence of CET activity on HDLP CS but had positive correlation between HDLP apoE and HDLP CS in the serum. Thus, defects of reverse CS transport may be induced not only by changes in CET activity but also by apoE distribution among lipoproteins of different classes.

Adult↗
PubMed1996

[Conformation of apolipoprotein B-100--structure and functional classification of low density lipoproteins].

Based on the model of an oil drop of the apolipoprotein B-100 lipoproteins (apo-B-100 LP) structure and physico-chemical and antigenic differences in their individual classes, an alternative model has been developed. If the apo-B-100 contains one hydrophilic ligand domain, two hydrophobic domains with predominating alpha-structures and two domains with predominating beta-folding, the molecule may acquire the conformation of a disc, one side of which is hydrophilic, while the other one is hydrophobic. The hydrophilic side of the disc comprises the ligand domain; on the hydrophobic side apo-B-100 forms nonpolar lipids. Apo-B-100 LP has the structure of a bilayer protein-lipid disc. Stepwise alterations in the apo-B-100 disc configuration during lipolysis determine the conversion of apo-B-100 LP in the blood flow: very low density LP-->low density LP. Conformational changes in the apo-B-100 disc form the basis for antigenic differences in each class of LP. Changes in the conformation of apo-B-100 disc in LP induce lipolysis and the formation of cholesterol esters circulating in the functional cycle, in which the cell is the indispensable step. The functional turnover of cholesterol in tissues integrates into one cycle lipoproteins of both high and low density. Equimolar substitution of triglycerides for more hydrophobic cholesterol esters associated with the C-terminal domain of apo-B-100 receptor of the cell. During triglyceride transport the apo-B-100 disc consecutively acquires three configurations--initial, intermediate and final. This hypothesis made the basis for functional classification of apo-B-100 LP in which the initial, intermediate and final classes can be singled out. Blockade of the functional cycle of cholesterol at various stages gives rise to individual hyperlipoproteinemia phenotypes. LP of one class only are accumulated in the blood for each type: the initial class in type III, the intermediate class in type IIb and the final class in type IIa. Each of the three apo-B-100 LP classes is distinguished for its peculiar structure and significant differences in the mechanism of their reception by the cells.

Apolipoprotein B-100↗
PubMed1996

[Blood flow lipid transport from viewpoint of protein biochemistry].

In accordance with the principles of protein biochemistry, apolipoprotein is the only protein which: 1) forms a protein-lipid complex (PLC) mainly from one class of lipids; 2) determines its functional role; 3) causes dyslipidemia in the genetic destruction of apoproteins or their quantitative ratio. Blood flow lipid transport is based on the functional specificity of their apoproteins; each apoprotein forms a functionally independent PLC; each PLC is formed from one class of lipids; each PLC has one protein-vector; each protein-vector interacts only with receptor. The basis of a united cycle functioning in lipid transport is the difference of primary apoprotein structure. Cholesterol performs an auxiliary function in triglyceride transport by providing circulation in the functional cycle. Lipid transport in blood flow is based, first, on the principles of protein biochemistry and, second, on those of lipidology.

Apolipoproteins↗
PubMed1995

[Lipid transport in blood from the protein chemistry viewpoint].

In agreement with the protein biochemistry principles apolipoprotein is considered to the only protein which: 1) forms protein-lipid complex (PLC) based on one lipid grade; 2) determines its functional significance; 3) causes the development of dyslipidemia at genetic disorder of quantitative and qualitative protein composition. The lipid transport in blood flow is based on high functional specifics of each of apoproteins; each apoprotein forms functionally separate PLC; each PLC has got one protein-vector; each protein-vector interacts with only one receptor. The basis of united cycle functioning in lipid transport is the difference of primary apoprotein structure. Cholesterol conducts an auxiliary function in triglyceride transport providing circulation in functional cycle. The lipid transport in blood flow is based first of all on protein chemistry principles and secondary--on lipidology principles.

Apolipoproteins↗
PubMed1995

[Role of cholesterol esters in triglyceride transport].

Biosynthesis of cholesterol esters in the blood flow and their function are determined by the fact that these compounds are the sole endogenously synthesized molecules whose hydrophobicity is higher than that of triglycerides transferred by the blood. Within the structure of intermediate density lipoproteins, cholesterol esters substitute for triglycerides during association of apoprotein B-100 with the C-terminal lipid-binding domain. Substitution of the liquid-crystalline phase of triglycerides for the corresponding phase of cholesterol esters results in a significant alteration of the apoprotein B-100 conformation and the formation of low density lipoproteins. Within the structure of low density lipoproteins, the N-terminal domain (apoprotein B-100 ligand) acquires an active conformation and an ability to interact with cell membrane receptors, thereby facilitating their absorption of low density lipoproteins. Cholesterol synthesis in the blood is an independent step in triglyceride transport. Inhibition of cholesterol ester synthesis into high density lipoproteins and their conversion into intermediate density lipoproteins is unaccompanied by the acquisition by apoprotein B-100 of a final conformation or by the formation of low density lipoproteins. Remnants of intermediate density lipoproteins having an intermediate conformation of apoprotein B-100 and the inactive position of the domain ligand are accumulated in the blood. This results in the development of IIb type hyperlipoproteinemia. Resumption of conversion of cholesterol esters from high density lipoproteins into intermediate density lipoprotein remnants normalizes the triglyceride transport. The final conformation of apoprotein B-100 can be modelled by substituting triglycerides in intermediate density lipoprotein remnants for another substance whose hydrophobicity is similar to that of cholesterol esters (dolichol, probucol).(ABSTRACT TRUNCATED AT 250 WORDS)

Anticholesteremic Agents↗