PubMed Health⌕ Search

Biomedical subjects

I A Sobenin

Publications and source records attributed to I A Sobenin.

At least 19 recordsLinked to original sources
PubMed2005

Desialylation decreases the resistance of apo B-containing lipoproteins to aggregation and increases their atherogenic potential.

Subfractions of apo B-containing lipoproteins (VLDL and intermediate-density lipoproteins) with reduced content of sialic acid were found in human blood. These lipoproteins are characterized by high capacity to spontaneous association (aggregation) and stimulated accumulation of cholesterol in smooth muscle cells of human aortic intima. In vitro treatment of apo B-containing lipoproteins with alpha-2,6-sialidase and alpha-2,3-sialidase stimulated aggregation and increased the ability of these particles to potentiate cholesterol accumulation in smooth muscle cells of the intact human aortic intima. Probably, desialylation of various apo B-containing lipoproteins can occur in the blood; this process decreases their resistance to aggregation, and increases the ability of these particles to stimulate accumulation of cholesterol in human aortic intima cells, i.e. increases their atherogenic potential.

Analysis of Variance↗
PubMed2005

Phospholipid hydrolysis with phospholipases A2 and C impairs apolipoprotein B-100 conformation on the surface of low density lipoproteins by reducing their association resistance.

Modification of apolipoprotein B-100 conformation on the surface of LDL isolated from human blood was demonstrated by enzyme immunoassay with a panel of monoclonal antibodies to this protein. The study by the light transmission fluctuation method showed that incubation of LDL with phospholipases A2 or C led to association of LDL particles. This lipolytic modification seems to impair LDL surface properties inducing association of these particles, which can play an important role in lipid accumulation in the vascular wall and at early stages promote the development of atherosclerosis.

Apolipoprotein B-100↗
PubMed2005

Proteolysis of apoprotein B-100 impairs its topography on LDL surface and reduces LDL association resistance.

Serine proteinases (trypsin and chymotrypsin) cause destruction of apolipoprotein B-100 on the surface of human blood LDL. Incubation of LDL with these enzymes increases the mean size of LDL particles. Proteolysis of apolipoprotein B-100 induces changes in surface structure, destabilizes LDL particles, and reduces their association resistance. Presumably, this proteolytic modification of LDL with subsequent association of these particles plays an important role in accumulation of cholesterol in the vascular wall and in the development of early stages of atherosclerosis.

Agglutinins↗
PubMed2005

[Reduction of cardiovascular risk in primary prophylaxy of coronary heart disease].

The purpose of the study was to evaluate the effects of Allicor, an Allium sativum (garlic) preparation with prolonged activity, on 10-year prognostic risk of coronary heart disease (CHD), acute myocardial infarction (MI) and sudden death in patients with elevated and high risk of CHD. 79 patients with elevated and high risk of CHD were included in a double blind randomized placebo-controlled study. They underwent multifactor evaluation of cardiovascular risk by algorithms based on the results of Framingham and Munster studies. Prolonged (12 months) administration of Allicor significantly reduced the multifactor risk, which was demonstrated by a 13.2% (p = 0.005) reduction of prognostic 10-year risk of CHD in men, and a 7.1% (p = 0.040) reduction of the same parameter in women. Prognostic 10-year risk of MI and sudden death in men was reduced by 26.1% (p = 0.025) and did not change significantly in women. In men the main factor of cardiovascular risk reduction was the decrease of cholesterol and low-density lipoprotein concentration by 23.5 +/- 6.6 mg/dl (p = 0.004), and in women - the increase of high-density lipoprotein level by 2.8 +/- 1.5 mg/dl (p = 0.040). The results of the study demonstrate that prolonged Allicor therapy can be applied to the large category of patients who are in need of atherosclerosis prevention.

Adult↗
PubMed2005

[Allicor efficacy in lowering the risk of ischemic heart disease in primary prophylaxis].

AIM: To assess effects of allicor (a long-acting garlic drug) on the risk of ischemic heart disease (IHD) in primary prophylaxis of cardiovascular diseases. MATERIAL AND METHODS: A double blind placebo-controlled study investigated for a year changes in multifactorial risks of cardiovascular events or their complications in 167 patients with hyperlipidemia free of IHD. RESULTS: In men, intake of allicor for 12 months resulted in a 10.7% reduction of a 10-year absolute risk to develop IHD (p < 0.05) and decreased a 10-year absolute risk of acute myocardial infarction and sudden death by 22.7% (p < 0.05). In women, allicor prevented age-related cardiovascular risk (p < 0.05). Among lipid parameters, the greatest fall was observed for total cholesterol and LDLP cholesterol (p < 0.05) in men by 27.9 and 22.5 mg/dl, in women--by 11.4 and 10.8 mg/dl, respectively. CONCLUSION: Allicor is effective in reducing multifactorial risk of cardiovascular diseases.

Adult↗
PubMed2004

Low ionic strength promotes association of circulating modified LDL in human blood.

The resistance to association of circulating multiply-modified low-density lipoproteins (LDL) isolated from human blood and characterized by a decreased content of sialic acids in comparison with native LDL was studied by analysing light transmission fluctuations. LDL association was stimulated by decreasing environmental ionic strength. It is established that circulating modified LDL are less resistant to association than native LDL. Association of LDL in a medium with low ionic strength was irreversible. Probably, increased capacity to irreversible association determines the atherogenic properties of circulating modified LDL subfraction.

Arteriosclerosis↗
PubMed2004

Resistance of native and circulating modified low-density lipoproteins in human blood to association.

The resistance of native and circulating modified low-density lipoproteins from human blood to spontaneous and polyethylene glycol-induced association was studied by recording light transmission fluctuations. Circulating modified low-density lipoproteins were less resistant to association than native low-density lipoproteins. Polyethylene glycol-induced association of low-density lipoproteins was irreversible. Our results suggest that atherogenic activity of circulating modified low-density lipoproteins is associated with their increased predisposition to irreversible association.

Arteriosclerosis↗
PubMed2004

Antigenic differences between apo-B in native and circulating modified low-density lipoproteins.

The state of apo-B in native and circulating modified low-density lipoproteins was studied by solid-phase enzyme immunoassay. We studied the interaction of these particles with monoclonal antibodies to apo-B of low-density lipoproteins. Native and circulating modified low-density lipoproteins had different affinity for the studied antigens. Our results illustrate conformational changes in apo-B of circulating modified low-density lipoproteins compared to native low-density lipoproteins. These changes probably contribute to increased accumulation of particles in vascular cells and their transformation into foam cells giving way to atherosclerotic vascular lesions.

Antibodies, Monoclonal↗
PubMed2004

[Study of the antioxidant drug "Karinat" in patients with chronic atrophic gastritis].

A randomized double blind placebo-controlled trial of the drug karinat was carried out in patients with chronic multifocal atrophic gastritis. Karinat contains beta-carotene 2.5 mg, alpha-tocopherol 5 mg, ascorbic acid 30 mg and garlic powder 150 mg per tablet. Out of 66 patients, 34 received karinat, 32--placebo. Both karinat and placebo were administered for 6 months, one tablet twice a day. Karinat therapy improved digestion, the fibrogastroscopic pattern of mucosa, inhibited Helicobacter pylori infection, stimulated stomach activity, mitigated intestinal metaplasia and interfered with the epithelial proliferation of gastric mucosa. These therapeutic effects were more pronounced in the study group. On the whole, the effectiveness of the drug was significantly higher (29%). Karinat should be recommended for the management of chronic atrophic gastritis, a precursor of stomach cancer.

Anticarcinogenic Agents↗
PubMed2003

[Effect of long-acting garlic tablets "allicor" on the incidence of acute respiratory viral infections in children].

AIM: To elucidate the prospects administration of allicor (long-releasing garlic tablets) in prevention of acute respiratory diseases (ARD) in children vs benzimidazole (dibazole). MATERIAL AND METHODS: At the first stage, tolerance of allicor (600 mg/day) and its effects on ARD morbidity were investigated in an opened 5-month study in 172 children aged 7-16 years compared to 468 controls. As the second stage, the effects of allicor (300 mg/day) on ASRD morbidity were investigated in a double-blind placebo-controlled randomized 5-month trial in 42 children aged 10-12 years in comparison with 41 placebo-treated children and 73 benzimidazole-treated children. RESULTS: At the first stage of the study allicor was not observed to induce gastrointestinal side effects in children at any dosage while ARD morbidity was reduced 2-4-fold as compared to the controls. At the second stage of the study allicor reduced ARD morbidity 1.7-fold compared to placebo and 2.4-fold vs benzimidazole. There was no significant difference in ARD morbidity between placebo- and benzimidazole-treated groups. Health index in allicor-treated group was 1.5-fold higher as compared either to placebo- or benzimidazole-treated children. CONCLUSION: Thus, the results of this study have demonstrated that allicor is effective for non-specific prevention of acute respiratory infections in children and has no side effects. ARD prevention with benzimidazole appeared ineffective in placebo-controlled study, so the development of new useful and safe preparations is of ultimate importance.

Adolescent↗
PubMed2003

[Atherogenic cholesterol-containing circulating immune complexes--one of the components of the serum in patients with systemic lupus erythematosus].

To estimate concentrations of cholesterol (CS) and immune complexes (IC) in patients with systemic lupus erythematosus (SLE), we examined 20 new SLE cases (all women, mean age 30.2 +/- 6.6 years, duration of the disease 2.6 +/- 1.5 years) with no history of corticosteroids treatment. The control group of 20 healthy patients was matched by age, body mass index and absence of risk factors. CS in IC precipitates was estimated by enzyme assays (kits by Boehrinnger Mannheim GmbH, Germany). The level of CS-containing IC (CS-IC) was significantly higher in SLE patients (11.9 +/- 2.7 mcg/ml) versus controls (6.0 +/- 2.2 mcg/ml, p < 0.05). The lipid spectrum was similar in the patients and controls. A significant positive correlation was registered between LDP CS and CS-IC levels (r = 0.774; p = 0.041). Association with other indices of blood lipid spectrum (total CS, triglycerides, HDP CS) was not observed. Thus, elevated level of CS-IC and association with LDP CS may be involved in atherogenesis of SLE patients.

Adolescent↗
PubMed2001

Human plasma trans-sialidase causes atherogenic modification of low density lipoprotein.

In earlier studies we have found that incubation of low density lipoprotein (LDL) with autologous blood plasma-derived serum leads to a loss of sialic acid from lipoprotein particles. In this study we demonstrated that sialic acid removed from LDL was transferred to glycoconjugates of lipoproteins, glycoproteins and sphingolipids of human serum. This showed that human serum contained the trans-sialidase activity. Gel-filtration chromatography of human blood serum demonstrated the presence of trans-sialidase activity in lipoprotein subfractions as well as in lipoprotein-deficient serum. Trans-sialidase (about 65 kDa) was isolated from lipoprotein-deficient serum using affinity chromatography carried out with Neu5Acalpha2-8Neu5Ac-sepharose FF-6. Optimal pH values for the trans-sialidase were 3.0, 5.0 and 7.0. Calcium and magnesium ions stimulated the enzyme activity at millimolar concentrations. Isolated enzyme can remove sialic acid from LDL, IDL, VLDL, and HDL particles (in decreasing rate order). Serum trans-sialidase transferred sialic acid from glycoconjugates of plasma proteins (fetuin, transferrin) and gangliosides (GM3, GD3, GM1, GD1a, GD1b). Sialylated glycoconjugates of human blood erythrocytes also served as substrate for serum trans-sialidase. We have found that sialic acid can also be removed from N- and O-linked glycans, sialylated Le(x) and Le(a), oligosialic acids, and sphingolipid carbohydrate chains. The rate of sialic acid release decreased in the following order: alpha2,6>alpha2,3>>alpha2,8. Transferred molecule of sialic acid can form alpha2,6, alpha2,3 and to a lesser degree alpha2,8 linkage with galactose, N-acetyl-galactosamine or sialic acid of acceptors. The glycoconjugates of erythrocytes, lipoprotein particles, plasma proteins, neutral sphingolipids and gangliosides may serve as acceptors of transferred sialic acid. Trans-sialidase-treated native LDL becomes desialylated and then can induce cholesteryl ester accumulation in human aortic intimal smooth muscle cells. Thus, trans-sialidase may be involved in the early stages of atherogenesis characterized by foam cell formation.

Arteriosclerosis↗
PubMed1998

Low-density lipoprotein modification occurring in human plasma possible mechanism of in vivo lipoprotein desialylation as a primary step of atherogenic modification.

We previously found in human blood a fraction of low-density lipoprotein (LDL) that is characterized by a reduced content of sialic acid. Desialylated LDL also has a low neutral carbohydrate level, decreased content of major lipids, small size, high density, increased electronegative charge and altered tertiary apolipoprotein B structure. Unlike native LDL, this fraction of desialylated (multiple-modified) LDL induces the accumulation of lipids in smooth muscle cells cultured from unaffected human aortic intima, i.e. it exhibits atherogenic properties. In this study, we attempted to elucidate the mechanism of desialylation and other changes in the multiple-modified LDL by investigating the possibility of LDL modification by different cells and the blood plasma. A 24-h incubation at 37 degrees C of lipoprotein with intact endotheliocytes, hepatocytes, macrophages and smooth muscle cells or cell homogenates did not cause alterations either in the physical properties or in the chemical composition of native LDL. On the other hand, a significant fall in the lipoprotein sialic acid level was observed already after a 1-h incubation of native LDL with an autologous plasma-derived serum. While LDL sialic acid level continuously decreased, LDL became capable of inducing the accumulation of total cholesterol in the smooth muscle cells cultured from unaffected human aortic intima after 3 h of incubation. Starting from the sixth hour of LDL incubation with serum, a steady decrease in the lipoprotein lipid content was observed as well as the related reduction of LDL size. Following 36 h of incubation, an increase in the negative charge of lipoprotein particles was also seen. Prolonged incubation of LDL with plasma-derived serum (48 and 72 h) leads to the loss of alpha-tocopherol by the LDL as well as to an increase in LDL susceptibility to copper oxidation and to accumulation of cholesterol covalently bound to apolipoprotein B, a marker of lipoperoxidation. Degradation of apolipoprotein B starts within the same period of time. Hence, desialylation of LDL particles represents one of the first or the primary act of modification which is, apparently, a sufficient prerequisite for the development of atherogenic properties. Subsequent modifications just enhance the atherogenic potential of LDL. The loss of sialic acid by LDL occurred at neutral pH and was not inhibited by the sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid. The [3H]sialic acid removed from LDL was not found in free form, but in the plasma fraction precipitated by trichloroacetic acid. These data along with the fact that cytidine-5'-triphosphate inhibited LDL desialylation suggest that enzymes close to sialyltransferases play a role in this process. Thus, this study demonstrated that the LDL modification processes imparting atherogenic properties to this lipoprotein can take place in human blood plasma. Multiple modification of LDL is a cascade of successive changes in the lipoprotein particle: desialylation, loss of lipids, reduction in particle size, increase of its electronegative charge and peroxidation of lipids.

Aorta↗
PubMed1998

Antioxidant content in low density lipoprotein and lipoprotein oxidation in vivo and in vitro.

UNLABELLED: Human blood contains naturally occurring multiple-modified low density lipoprotein (nomLDL) capable of inducing the accumulation of cholesteryl esters in the cells of human aortic intima. NomLDL is desialylated particles of small size with an increased electronegative charge which can be separated from native low density lipoprotein (LDL) by lectin chromatography. The purpose of this study was to determine the content of antioxidants in native and nomLDL obtained from healthy subjects and from patients with coronary heart disease as well as to elucidate a possible relationship between the level of antioxidants and the degree of in vivo and in vitro LDL oxidizability. The apoB-bound cholesterol level in native and nomLDL of healthy subjects was 0.25 +/- 0.08 and 0.28 +/- 0.05 mol/mol apoB, respectively. The level of apoB-bound cholesterol in native LDL of coronary atherosclerosis patients showed no significant difference from that in healthy subjects' native lipoprotein. At the same time, the level of apoB-bound cholesterol in patients' nomLDL was 7-fold higher than in native LDL. The average duration of the lag phase of native LDL oxidation did not show a significant difference between the lipoprotein of healthy subjects and coronary atherosclerosis patients. The lag phase of nomLDL obtained from healthy subjects and patients was significantly shorter (3- and 6-fold, respectively) than for their native LDL. The latter finding points to their increased susceptibility to in vitro oxidation. Oxidizability of total LDL preparations correlated positively with their nomLDL content. The content of all the antioxidants studied (coenzyme-Q10, alpha- and gamma-tocopherols, beta-carotene and lycopene) in nomLDL was 1.5- to 2-fold lower than in native LDL. The level of apoB-bound cholesterol in nomLDL, correlated positively with the ubiquinone-10 content and showed negative correlation with ubiquinol-10 and beta-carotene levels. On the other hand, the content of apoB-bound cholesterol in native LDL correlated positively with the ubiquinol-10 level. Susceptibility of nomLDL to in vitro oxidation exhibited negative correlation with alpha-tocopherol and beta-carotene levels and a positive correlation with the ubiquinone-10 content. On the contrary, oxidizability of native LDL correlated positively with the ubiquinone-10 level. CONCLUSIONS: (a) elevated apoB-bound cholesterol level in nomLDL of coronary atherosclerosis patients indicates that peroxidation of lipids occurs in vivo; (b) in vivo lipoperoxidation in nomLDL is corroborated by increased proportion of oxidized form of coenzyme-Q10; (c) content of lipid-soluble antioxidants in nomLDL is lower than in native lipoprotein; (d) nomLDL has a higher susceptibility to in vitro oxidation than native LDL; (e) it is necessary to use isolated subfractions of native LDL and nomLDL, but not total lipoprotein preparations, to study the mechanisms of lipid peroxidation.

Adult↗
PubMed1998

Optimization of the assay for sialic acid determination in low density lipoprotein.

Sialic acid level in blood plasma and circulating glycoproteins is considered to be a marker for a number of pathologic conditions, including atherosclerosis, cancer, etc. The precise measurement of sialic acid level is an important laboratory procedure to allow correct interpretation of results. Colorimetric methods commonly used for the measurement of sialic acid are not highly specific, as interfering substances may alter the results. Among these, malondialdehyde and other aldehydes play the decisive role. In the circulation, aldehydes are commonly produced during lipid peroxidation in the lipid core of lipoprotein particles, especially low density lipoprotein (LDL). To establish the impairment to the sialic acid determination in LDL introduced by interfering substances, the optimized assay based on Warren's traditional method was developed and tested in 606 LDL samples. The optimization implies the comparison of color developed using the standard Warren procedure with that due to contaminating agents, mainly thiobarbituric acid-reactive substances (TBARS). In LDL stored at 4 degreesC, the estimates obtained by the modified procedure were 41.5% or 30.1 nmol/mg lower, on average, compared to the standard procedure (n = 45, P < 0.0001). Even in LDL stored at -70 degreesC, sialic acid estimates obtained by the modified procedure were 6.6% or 3.6 nmol/mg lower, on average, compared to the standard measurement (n = 561, P < 0.005). Thus, the modified procedure avoids significant distortion of the measurement induced by the presence of interfering agents.

Colorimetry↗
PubMed1997

Antiatherosclerotic and antiatherogenic effects of a calcium antagonist plus statin combination: amlodipine and lovastatin.

Recently, the Regression Growth Evaluation Statin Study (REGRESS) demonstrated the synergistic, antiatherogenic effect of lipid-lowering therapy with pravastatin in combination with calcium antagonists. This combination retarded the progression of stenosis and reduced the number of new lesions more effectively than did statin therapy alone. In the present study, our objective was to elucidate the mechanism of this more pronounced effect of the statin-calcium antagonist combination on the atherosclerotic lesion. Smooth muscle cells cultured from the subendothelial intima of the human aorta were incubated with whole blood serum or with low-density lipoprotein (LDL) taken from patients cotreated with lovastatin and amlodipine. Serum added to the cells cultured from the atherosclerotic lesion reduced cell cholesterol. Such an antiatherosclerotic effect of cotreatment with amlodipine-lovastatin was revealed in this study and was more pronounced than the effect of treatment with either amlodipine or lovastatin alone. LDL isolated from atherogenic plasma stimulated cell cholesterol accumulation. Treatment with amlodipine alone and the amlodipine-lovastatin combination ameliorated the atherogenic effect of LDL. As compared with amlodipine alone, the combination demonstrated a considerably higher antiatherogenic effect on LDL atherogenicity. Amlodipine-lovastatin cotreatment increased sialic acid and decreased the susceptibility of LDL to oxidation more effectively than amlodipine alone. In addition, combination therapy reduced the LDL negative charge, while amlodipine alone was impotent. These findings may serve as an explanation of the more pronounced antiatherogenic effect at the lipoprotein level of amlodipine-lovastatin combined therapy compared with amlodipine therapy alone.

Amlodipine↗
PubMed1996

Characteristics of low density lipoprotein isolated from circulating immune complexes.

Circulating immune complexes (CIC) containing low density lipoprotein (LDL) were recently found in the blood of patients with coronary atherosclerosis. In the present study, we investigated the chemical composition and physical characteristics of the lipoprotein constituents of these CIC. CIC were isolated from the blood of atherosclerotic patients by affinity chromatography using anti-human immunoglobulin G-agarose. Low density lipoprotein of these complexes (CIC-LDL) was obtained by ultracentrifugation. CIC-LDL was compared with free circulating LDL isolated from the blood plasma of the same patients. Plasma LDL was fractionated by lectin-chromatography on RCA120-agarose to obtain desialylated LDL (atherogenic) and sialylated LDL (nonatherogenic). Both CIC-LDL and desialylated LDL, but not native (sialylated) lipoprotein, induced a 1.8- to 3-fold increase in the intracellular contents of free and esterified cholesterol of cells cultured from grossly normal areas of human aorta. The sialic acid level in CIC-LDL was 1.3- and 2.1-fold lower than in desialylated or native LDL, respectively. The neutral lipid and phospholipid contents of CIC-LDL and desialylated LDL were reduced as compared to native LDL. The levels of lipid-oxidation products, thiobarbituric acid-reactive substances and hydroperoxides, were similar in all lipoprotein preparations. However, desialylated LDL and CIC-LDL had an elevated oxysterol content. Gradient ultracentrifugation revealed that CIC-LDL particles had a higher density than native LDL. The mean diameters of native, desialylated and CIC-LDL accounted for 24.0, 21.3 and 19.5 nm, respectively. Like desialylated LDL, CIC-LDL displayed a higher electrophoretic mobility compared with that of native LDL. Thus, LDL obtained from circulating immune complexes appears to be a multiple-modified lipoprotein possessing many similarities to desialylated LDL. It was also found that the LDL content of circulating immune complexes correlates well with the desialylated LDL level in human plasma but not with the total LDL concentration. We believe that desialylated LDL predominately interacts with antibodies forming immune complexes. Taken together, our findings suggest that multiple-modified desialylated LDL is the circulating autoantigen for anti-LDL autoantibodies.

Adult↗