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Biomedical subjects

A N Klimov

Publications and source records attributed to A N Klimov.

At least 19 recordsLinked to original sources

Social factors and increase in mortality in Russia in the 1990s: prospective cohort study.

OBJECTIVE: To determine the association between social factors and the increase in mortality in Russia in the 1990s. DESIGN: Prospective population cohort study. SETTING: Saint Petersburg, Russia. PARTICIPANTS: Two cohorts of men aged 40-59 years randomly selected from district voting list: 3907 screened in 1975-7 and 1467 in 1986-8. MAIN OUTCOME MEASURES: Education, various health related measures, alcohol intake. Mortality in subsequent 10 years. RESULTS: There was no recorded increase in mortality in men with university degrees. The relative risk in the second cohort compared with the first was 0.92 (95% confidence interval 0.67 to 1.24). For participants with only high school education it was significantly higher in the second cohort (1.32, 1.02 to 1.71). The most pronounced differences were found among participants with the lowest level of education, in which the relative risk was 1.75 (1.44 to 2.12). The same pattern held for coronary vascular disease and cancer mortality. CONCLUSION: In Russia men in the lower socioeconomic groups were most affected by the sharp increases in mortality in the 1990s.

Adult↗

On the ability of high density lipoproteins to remove phospholipid peroxidation products from erythrocyte membranes.

To study the transfer of oxidized phospholipids from cell membranes to high-density lipoproteins (HDL), human Cu2+-oxidized erythrocyte membranes were incubated with HDL3 subfraction for 17 h at 37 degrees C followed by isolation of the supernatant, precipitation from it of HDL3, and determination of lipid peroxide products (LPP) in them. The incubation increased the content of lipid hydroperoxides in HDL3 significantly (by 32 and 40% calculated per ml of sample or mg of protein) and of malondialdehyde (by 27 and 34%, respectively) compared to control (incubation of HDL3 alone). The content of conjugated dienes did not change significantly. Fluorescence analyses of isolated HDL3 particles showed that the content of fluorescent products (lambdaex = 365 nm, lambdaem = 430 nm) in them was 2.5 times higher than in control, and the number of binding sites for the 1-anilinonaphthalene-8-sulfonic acid probe decreased by 22%. This also confirms accumulation of LPP in the lipoprotein subfraction. It seems likely that an increase in LPP (at least hydroperoxides) in HDL3 after their incubation with oxidized membranes occurs via transport of phospholipids containing LPP from erythrocyte membranes to lipoproteins. The data on the ability of HDL3 to accept LPP from erythrocyte membranes in vitro suggest that HDL3 may have a protective action on cell membranes undergoing oxidation in vivo as well.

Anilino Naphthalenesulfonates↗

The total and HDL-cholesterol levels in populations of St. Petersburg (Russia) and Leipzig (Germany).

BACKGROUND AND AIM: In the early 90s an increase in coronary heart disease (CHD) mortality in post-communist countries was observed. Based on the lipid theory of the pathogenesis of atherosclerosis, we looked to see whether these changes were accompanied by changes in blood lipid profiles and how lipid levels are related in a post-communist country with a relatively high standard of living (East Germany) and a country still facing economic troubles (Russia). METHODS AND RESULTS: This investigation was conducted in 1995-1997 by a cooperative program between the Department of Clinical Chemistry and Pathobiochemistry, University of Leipzig, Leipzig, Germany and the Department of Biochemistry, Institute for Experimental Medicine, St. Petersburg, Russia. The Russian part of the study included 1646 subjects and the German part 3189 subjects. The blood lipids were measured using a dry-chemistry analyzer (Reflotron). Russian and German males had almost the same level of total cholesterol with a significantly lower level of HDL-C in Russians. A significantly lower level of HDL-C was also observed in Russian females. Differences were in range 2-3 mg/dl for males and 8-13 mg/dl for females. In St. Petersburg, almost 40% of all screened young males (age < 30 yr) had hypoalphacholesterolemia. In the St. Petersburg study carried out in 1986-1988, in age group 40-49 years around 6% of those screened had HDL-C lower than 35 mg/dl. In 1995-1997 this number increased to 36%. The number of subjects with HDL-C less than 30 mg/dl in 1986-1988 was only 2.4% and in 1995-1997, 12.3%. CONCLUSION: There is a dramatic decrease in HDL-C in the Russian population, probably due to the socioeconomic factors which began to develop after the fall of communist.

Adult↗

"Essential" phospholipids versus nicotinic acid in the treatment of patients with type IIb hyperlipoproteinemia and ischemic heart disease.

In patients with moderate, dietary noncorrigible hyperlipoproteinemia type IIb and ischemic heart disease, treatment with nicotinic acid is limited by the side effects of the drug. In 100 patients, 6-month treatment with nicotinic acid (n = 50) or "essential" phospholipids (EPL); Lipostabil, manufacturer: Rhône-Poulenc Rorer) (n = 50) indicated comparable efficacy for both substances: Significant (p < .001) reductions of serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride values were similar in both groups, while nicotinic acid increased high-density lipoprotein (HDL) cholesterol significantly (p < .01) better than Lipostabil. A detailed analysis of ultracentrifugal lipoprotein profiles, hydroperoxide concentrations in LDL, and cholesterol-accepting properties of HDL in a small number of Lipostabil- and nicotinic acid-treated patients revealed favorable shifts in the lipoprotein profile, significant (p < .05) reductions of LDL hydroperoxides, and favorable increases of the most antiatherogenic HDL2b subfraction only in the Lipostabil-treated group. Clinically, both medications reduced the intensity and number of angina pectoris attacks per week (p < .05), but only Lipostabil-treated patients significantly (p < .05) increased their working capacity in the veloergometric test. Since in the nicotinic acid-treated group dropouts (nine patients, eight related to the drug) and side effects [14] exceeded those in the Lipostabil-treated group (two dropouts not related to the drug, no side effects), it is suggested that Lipostabil is a preferable alternative in the treatment of patients with moderate, dietary noncorrigible hyperlipoproteinemia IIb and ischemic heart disease.

Cholesterol, HDL↗

[The use of tactivin for treating patients with IHD].

Immunomodulating drug tactivin was used for treatment of 29 IHD patients with low T-suppressor activity and high cell sensitization to apoprotein B-containing lipoproteins and with lipoprotein-antibody immune complex detected in the blood. Tactivin was injected subcutaneously in the dose 10 micrograms (5 injections for 12 days). Tactivin treatment normalized T-suppressor activity, lowered concentration of plasma lipoprotein-antibody immune complex and improved clinical course of IHD. The beneficial effect of tactivin was observed in 70% of patients during 2 months. 30% of patients needed a second course of treatment of recover normal immunological and clinical indices. The treatment with tactivin of IHD patients must be combined with application of routine antianginal drugs.

Adjuvants, Immunologic↗

[Spectroscopic study of the mechanism of cholesterol interaction with apolipoproteins: a model of cholesterol-synthetic apolipoprotein A-I fragment].

To investigate the mechanism of cholesterol binding to apolipoproteins, a fragment of human apolipoprotein A-I involving its amino acid residues 144-164 has been synthesized. The interaction of this peptide (both native and having modified functional groups) with cholesterol in a water-alcohol medium has been studied, using fluorescence and circular dichroism techniques as well as NMR NOE spectroscopy. It has been found that the oligopeptide is able to form complexes with one and two cholesterol molecules, the association constant being as high as 10(8) M-1. The interaction involves hydrogen bonds formed by the cholesterol OH-group as well as hydrophobic interaction of the nonpolar groups of cholesterol and the peptide. The latter requires a specific conformation, i.e., the formation in the peptide molecule of a "cavity" at the expense of ionic coupling between the carboxylate groups in Asp or Glu side chains and the guanidinium groups of the protein. At pH 6.3, the OH-group of cholesterol becomes involved in the H-bond system which includes a COOH-group of Asp and two imidazole groups of His, one of which is in a neutral and the other one in a protonated from.

Amino Acid Sequence↗

[Cryohemosorption--a method of removal of lipoprotein-antibody immune complexes and other atherogenic substances in patients with atherosclerosis].

The efficacy of extracorporeal cryohemosorption was estimated in the treatment of atherosclerotic patients in terms of the autoimmune theory of the pathogenesis of this disease. There was a slight decrease in the plasma levels of total cholesterol and triglycerides, there was over 2-fold reduction in the plasma levels of fibrinogen and fibronectin. All major components of apo B-containing lipoproteins and immunoglobulin G were found as part of the cryoprecipitate. An extremely high concentration of lipid hydroperoxides in the precipitate suggest that cryoprecipitation removes not only autoimmune complexes, but highly-atherogenic peroxide-modified lipoproteins. The three-fold decrease in the levels of lipoprotein-antibody complexes resulted in lower atherogenicity of apo B-containing lipoproteins. It is suggested that the mechanism responsible for beneficial clinical action of cryohemosorption sessions is largely associated with the removal of autoimmune lipoprotein-antibody complexes and peroxide-modified apo B-containing lipoproteins than correction of lipid metabolism.

Adult↗

[Jejunoileal bypass in the prevention and treatment of clinical manifestations of atherosclerosis in patients with morbid obesity].

Jejunoileostomy effects on blood lipids and cardiovascular system were investigated in obese patients. They were found to lose 30% of their body mass within 6 postoperative months with parallel reduction in concentrations of total cholesterol, triglycerides, LDL and VLDL cholesterol and apoprotein B. These changes persisted for 4.5 years of the follow-up. The surgery in males has a more pronounced effect on blood lipids than in females. Significant changes were not registered in post- and preoperative levels of HDL cholesterol and apolipoprotein A-1. Jejunoileostomy promoted a fall in blood pressure, a rise in exercise tolerance, alleviation of atherosclerosis symptoms.

Adolescent↗

[Does the cholesterol content in blood cells depend on its level in plasma?].

The cholesterol content in human erythrocytes, granulocytes and the total leucocyte fraction with varying levels of plasma cholesterol has been studied. There was no correlation between the cell cholesterol content and the levels of total, LDL and HDL cholesterol in the plasma. The mean cholesterol content in one cell has been found to be equal to 1.26 x 10(-13) g in the erythrocytes, 2.08 x 10(-12) g in the granulocytes and 3.35 x 10(-12) g in the total leucocyte fraction.

Cholesterol↗

Antioxidative activity of high density lipoproteins in vivo.

The present study consists of experimental and clinical investigations. It was shown that a single intravenous injection of a large dose of human HDL3 (200 mg protein) to rabbits with induced hypercholesterolemia (plasma cholesterol 500-700 mg/dl) was accompanied by a significant elevation of plasma HDL and led to a decrease (P < 0.05) of conjugated dienes and trienes by 20-30% after 6 h. Conjugated dienes remained stable for 24 h after HDL administration. In the clinical investigations a weak but statistically significant negative correlation (r = 0.262; P = 0.006) between HDL cholesterol and the content of conjugated dienes in the plasma of a total group of healthy subjects and patients with coronary heart disease (CHD) was found. The data allowed us to conclude that, in addition to other antioxidative systems, HDL also take part in the protection of plasma lipids from peroxidation.

Animals↗

Increased risk of coronary heart disease death in men with low total and low-density lipoprotein cholesterol in the Russian Lipid Research Clinics Prevalence Follow-up Study.

BACKGROUND: A continuously increasing risk of coronary heart disease with increasing levels of cholesterol has been reported by many observational and experimental studies. However, this type of association has not been observed in studies in the Russian Lipid Research Clinics. METHODS AND RESULTS: Twelve-year coronary heart disease mortality among 40- to 59-year-old men was analyzed in the Moscow and St Petersburg examines in the Russian Lipid Research Clinics Program. The baseline survey examined 6431 men fasting and free of prevalent coronary heart disease. Lipids and lipoproteins, blood pressure, body mass, education level, alcohol intake, and smoking history were obtained. Mortality follow-up was based on contacts with participants or their relatives or neighbors. Coronary heart disease mortality was analyzed based on risk factor levels and was further divided into rapid and nonrapid deaths. A J-shaped cholesterol-coronary heart disease risk function was present for both total and low-density lipoprotein cholesterol. Further examination showed hypocholesterolemic men to have lower low-density and higher high-density lipoprotein cholesterol, higher alcohol consumption, leaner body mass, and less education than men with normal or high cholesterol levels. When education level was considered, the J-shaped risk function was present only among men with less than a high school education. When deaths were classified into rapid (less than 24 hours after onset of symptoms) and nonrapid, the J-shaped risk function was restricted to rapid deaths. CONCLUSIONS: The results of disclose a sizeable subset of hypocholesterolemics in this population at increased risk of cardiac death associated with lifestyle characteristics.

Cholesterol↗

On the mechanism of cholesterol interaction with apolipoproteins A-I and E.

It is shown that cholesterol may interact with some substances containing the guanidine group (guanidine itself, arginine, metformin and dodecylguanidine bromide) and with arginine-rich proteins--apoproteins A-I and E. In the latter case the interaction produces the formation of cholesterol-apoprotein complexes. Analysis of such complexes has shown that one apo A-I molecule binds 17-22 and one apo E molecule binds 30-35 sterol molecules, which approximately corresponds to the amount of arginine residues in these proteins. Formation of cholesterol-apoprotein complexes has been suggested to occur due to: (1) formation of hydrogen bond and/or ion-dipole interaction between cholesterol hydroxyl and guanidine groups of the apoprotein arginine residues and (2) hydrophobic interaction of the cholesterol aliphatic chain with nonpolar side chains of the amino acids occupying the third position from arginine in the protein molecule.

Amino Acid Sequence↗