[Introduction into PPPM: experience of the past and tomorrow's reality].

Health service today is on the verge of broad changes. The intensive practical application of the achievements of genomics, proteomics, metabolomics and bioinformatics has significantly deepened and continues to deepen our view of the pathological processes taking place at a level of biostructures. In the nearest future this progress will give medical practitioners the opportunity to focus on a subclinical stage of the disease, i.e. on the earliest stages of the pathological process. This will require the prediction of disease development risks, subclinical diagnostics with the precise staging of the pathological process, and, finally, the application as early as possible of targeted pharmacotherapeutic methods in order to prevent the manifestation of the disease or its progression into more severe stages. All these principles create the framework of a fundamentally new "3P" strategy in medicine: predictive, preventive and personalized medicine.

[Effect of tactivin on the behaviour and learning in rats].

The action of the immunocorrective agent tactivin on CNS functional activity was studied in an experiment using outbred white rats. The drug was shown to affect the animals' behaviour in an elevated cross-shaped maze including learning capacity and ability to overcome functional disorders of conditioned active avoidance response. The data obtained suggest anti-stress activity of tactivin.

[Immunobiologically active compounds from skin].

This paper describes physiochemical and biological properties of 3 immunologically active compounds extracted by acetone from porcine skin. High pressure gel chromatography confirmed their heterogeneity. RP-HPLC of compound 2 (C2 or K-activin) also characterizes it as a heterogeneous entity. It was shown to inhibit proliferation of cultured fibroblasts from human fetuses and exhibit weak activity in general anaphylactic reaction (anaphylactic shock) and skin anaphylactic reaction. A summary of data on immunologically active compounds are presented with special emphasis laid on acetone-extractable K-activin.

[Early non-invasive diagnosis of cardiovascular diseases].

The study was focused on the assessment of diagnostic significance of cholesterol content in the corneal layer of epidermis detected by the method based on experimental findings that suggest positive correlation between cholesterol levels in aortic endothelium and palm corneal epidermis. Surface cholesterol level was measured with the use of digitonin conjugate. A specially developed photometer proved a valuable tool for quantitative assay of surface cholesterol. Surface cholesterol was detected in epidermis of 649 patients with angiographically confirmed stenotic atherosclerosis. Its levels were significantly different in patients with different localization of atherosclerosis and in age-matched controls. The proposed test was found to be of great prognostic value even if its results were highly variable due to the necessity of separating free and conjugate-bound cholesterol. The enzyme assay of surface cholesterol in epidermis obviates this procedure which significantly improves reproducibility of results.

[Clinical and prognostic significance of free radical processes in patients with coronary heart disease].

The aim of the work was to evaluate the diagnostic and prognostic value of the characteristics of processes involving free radicals and of high-performance ECG (hpECG) in patients with coronary heart disease (CHD). A new method for early assessment of the severity of myocardial ischemia and its electric remodelling was developed. Malonic dialdehyde levels (MDA) following Cu-induced oxidation during 24 hr were shown to correlate with clinical features of CHD (functional class of angina, hpECG patterns). hpECG characteristics changed parallel to MDA levels, their frequency was related to the severity of CHD. Long-term prognosis of unstable angina (12 month follow-up) was aggravated in patients with MDA level of 100 nmol/ml. MDA concentration and its dynamics correlated with CHD severity and outcome of acute coronary syndrome (ACS): non-Q wave myocardial infarction and angina. All patients with ACS underwent its exacerbation within 5-7 days and had depleted plasma antioxidative system. MDA and hpECG dynamics can be used to evaluate ACS severity and prognosis as a new diagnostic approach to identifying CHD patients with the expected unfavourable outcome of the disease.

[Correlations between electrophysiological myocardial remodeling and parameters of free radical oxidation in patients with various forms of ischemic heart disease].

AIM: To investigate potentialities of a novel biochemical test assessing oxidative resistance of plasma as a marker of ischemic damage to the myocardium and to study this marker correlation with high-performance ECG parameters reflecting electrophysiological remodeling of the myocardium in patients with ischemic heart disease (IHD). MATERIAL AND METHODS: A total of 145 IHD patients entered the trial: 32 patients free of effort angina, 67patients with stable effort angina of functional class (FC) II-III, 56 patients with acute coronary syndrome (ACS) and 32 healthy controls. ACS patients were examined according to the following protocol: stage 1--6-12 hours since the disease onset, stage 2--at the end of the first 24 hours, stage 3--day 5-7 of the disease. In ACS patients the following outcomes (end points) were evaluated: recurrent myocardial infarction (MI), hospitalization because of exacerbation of IHD, documented potentially harmful arrhythmias and death within 1 year. High-performance ECG and a novel biochemical test of plasma oxidizability were used. The latter was determined by accumulation of malonic dialdehyde after 24 hours of incubation with 20 mcM of copper sulphate. RESULTS: A correlation was found between activity offree radical processes and electrophysiological remodeling of the myocardium by high-performance ECG. Amplitude and temporal characteristics of QRS complex and P wave can be used for follow-up of progression and severity of IHD in addition to standard electrocardiography. CONCLUSION: Unidirectional changes of high-performance ECG, plasma oxidizability and severity of IHD course allow using them as novel diagnostic tests of ischemic lesion and electrophysiological remodeling of the myocardium, for estimation of IHD severity.

[From transplantation of the thymus to molecular reconstruction of the immune system]. / Ot peresadki timusa k molekuliarnoi rekonstruktsii immunnoi sistemy.

The results of the first global grafting of the thymus and a thymus-sternum block are given. The grafting of immunocompetent organs in children with the Louis-Bar syndrome is shown to cause to a partial and in some cases significant recovery of immunological parameters. Thus, blast-cell transformation showed 10-40% increases, the titers of antibodies to Staphylococcus and Escherichia coli rose, and immunoglobulin A that was generally absent in these children before surgery appeared. The clinical effect of grafting was noticeably observed 20-30 days after surgery. The most significant parameters were as follows: cessation of sinusitis, rhinitis, bronchitis, and purulent skin lesions. Neurological syndromes improved: tremor and staggering gait diminished, ocular convergence normalized. Thereafter such operations were made in 27 patients with Bruton's disease and in 3 patients with lymphogranulomatosis. The grafting of immunocompetent organs led to the design of agents derived from the thyroid gland (Tactivin) and bone marrow (myelopid). The immunobiological and clinical effects of Tactivin in the past 15-20 years are given in detail. The basic principles in immunomodulating therapy with thymic agents are presented.

[Possibility of selective binding of HIV-1 infected cells by immunosorbents]. / Izuchenie vozmozhnosti selektivnogo sviazyvaniia infitsirovannykh VICh-1 kletok s pomoshch'iu immunosorbentov.

A study was made of a possibility of specific sorption of HIV-1 infected cells with gamma-fraction of AIDS patients' serum containing high titer-specific antibodies, immobilized on the silica matrix (C-3). The laboratory tests were made with the use of the monocyte culture [symbol: see text] chronically infected with HIV-1. In addition to a decrease of the cell count after sorption, there was a decline of the activity of antigen material in the samples (to 43% of the initial). The selectivity rates were 0.92 for immunosorbents and 0.29 for sorbents of the control group, that confirms and increase of the delay of the cells expressing HIV-1 proteins on a column with the immobilized gamma-fraction of AIDS patients' serum. The use of the synthesized immunosorbents in vivo may appear debatable. However, this method can be employed for preparative purposes.

[The immunomodulating properties of staphylotoxin]. / Immunomoduliruiushchie svoistva stafilotoksina.

The action of native staphylotoxin has been tested on T lymphocytes obtained from 21 healthy human donors. As revealed in this investigation, toxic action affects Fc-receptors to IgG, IgM and IgA. The dose-dependent effect of the preparation suggests its direct contacts with Fc-receptors of lymphocytic membranes. High doses of the toxin suppress the expression of Fc-receptors 6- to 12-fold, low doses of the toxin are capable of stimulating the expression of Fc gamma-receptors.

[Affinity hemosorbent for the binding of atherogenic lipoproteins]. / Affinnyi gemosorbent dlia sviazyvaniia aterogennykh lipoproteinov.

An affine hemosorbent, a product of covalent heparin immobilization on a solid matrix, has been proposed for the extraction of atherogenic lipoproteins. The sorbent has high capacity with respect to atherogenic lipoproteins and is selective with other blood constituents. Experimental hemosorption in animals demonstrated rapid sorbent regeneration and satisfactory hemo- and biocompatibility, therefore the new sorbent can be recommended for clinical application.

[Sorption decholesterolization of the blood]. / Sorbtsionnaia dekholesterinizatsiia krovi.

Results of haemosorption with the use of activated carbon IGI in patients with different diseases of the liver are given. It is shown that along with the toxic metabolites the method serves to remove a considerable quantity of cholesterol. It is surmised that haemosorption can become an effective method of control of hypercholesterolemia in atherosclerosis and its complications. The results of stand tests of sorbents specific for cholesterol are presented. A sorbent, synthesized from a metal-containing polymer was used for haemosorption in experiments on rabbits with alimentary hypercholesterolemia. Single haemosorption lasting 30 min led to a two-fold decrease of the cholesterol level in the blood and to a two-fold decrease of the damaged area in the aorta 4 weeks after operation.

[Hemosorption - a method of rapid elimination of cholesterol from the plasma and its effect on the regression of experimental atherosclerosis]. / Gemosorbtsiia - metod bystrogo udaleniia kholesterina iz plazmy krovi i vliianie ee na regressiiu eksperimental'nogo ateroskleroza u krolikov.

Hemosorption is a method of rapid control of hypercholesterolemia. A study of hemocompatibility of an alumosilicate sorbent which is relatively selective with respect to cholesterol demonstrated a possibility of its being used in hemosorption devices. Rabbits with spontaneous regression of two-month duration were given three hemosorption sessions. A drop in cholesterol and triglycerides was noted after each session. By the end of the experiment, the area of aortal atherosclerotic lesion was reduced twofold as compared to the controls (19% vs. 41%). Rapid regression of diffuse lipid deposits from the surface and marginal zones of the patches was observed. "New" secondary lipid deposits were absent. A possibility of using hemosorption in patients with pronounced hypercholesterolemia is discussed.

[Dynamics of the mental disturbances in primary biliary liver cirrhosis with allowance for a hemosorption procedure]. / Dinamika psikhicheskikh narushenii pri pervichnom biliarnom tsirroze pecheni s uchetom provedeniia gemosorbtsii.

The authors followed the time course of the psychic disturbances in 37 patients with primary biliary liver cirrhosis who received hemosorption as part of the combined therapy. The peculiarities of the psychic disturbances and their time course before and after the hemosorption were specified. It was found that after the hemosorption a regression of asthenoneurotic disturbances took place. However, the characteristic changes and elements of the psychoorganic syndrome developed in the course of the disease showed no positive dynamics.

[Quantitative characteristics of the T- and B-systems of immunity in healthy persons of different age groups]. / Kolichestvennaia kharakteristika T- i B-sistemy immuniteta u zdorovykh liudei raznykh vozrastnykh grupp

The authors carried out a complex immunomorphological study of the peripheral blood lymphocytes in 160 healthy persons of different age groups. The tests of spontaneous and complementary rosette formation of lymphocyte blasttransformation with PHA were used, assessing it by the H3-thymidine incorporation, lymphocyte straining by Coon's direct and indirect methods for detection of surface immunoglobulin receptors; G, A, and M immunoglobulins blood serum content was studied by Mancini's method. Mean indices characterizing the T- and B-populations of lymphocytes in persons of different age were calculated on the basis of these studies.

[The immunocorrective potentials of an antistaphylococcal immunosorbent in extracting staphylotoxin]. / Immunokorrigiruiushchie vozmozhnosti protivostafilokokkovogo immunosorbenta pri izvlechenii stafilotoksina.

The immunocorrective effect of antistaphylococcal adsorbent prepared on the basis of silochrome, a silica matrix, has been revealed in experiments on peripheral blood lymphocytes obtained from 18 donors. The expression of receptors on human immunoregulating cells has been suppressed by the addition of staphylotoxin at a toxic concentration into the system. The experiments have shown that immunosorption is capable of extracting the toxin from the solution to a considerable degree, thus preventing the suppression of the receptor apparatus of immunoregulating lymphocytes. Staphylotoxin has been found capable of forming complexes with plasma ingredients, which increases the adsorption capacity of the immunosorbent.

[Relation between resistance to oxidation and cholesterol acceptance of high density lipoproteins in patients with ischemic heart disease]. / Vzaimosviaz' mezhdu okislitel'noi ustoichivost'iu i kholesterin-aktseptornoi sposobnost'iu lipoproteinov vysokoi plotnosti u bol'nykh ishemicheskoi bolezn'iu serdtsa.

Cholesterol (CH) acceptance ability of high density lipoproteins (HDL) was assessed in 43 ischemic heart disease (IHD) patients, including patients with post-infarction cardiosclerosis and class II-III effort angina. CH acceptance ability of HDL was measured as increment of HDL CH after incubation with artificial CH-containing system. Oxidabilities of HDL and total plasma were estimated by quantitation of lipid peroxidation products (hydroperoxides and thiobarbituric acid-reactive substances - TBARS) after incubation with Cu(2+) ions. HDL fraction (after apo B lipoproteins removal) of IHD patients appeared to include 2 times less additive CH compared with donor's HDL despite lower (-12%) HDL CH level. Negative correlation (r =-0.38, p<0.05) existed between formed TBARS in HDL and HDL CH acceptance. In total plasma of IHD patients elevation of both formed TBARS and particularly hydroperoxides was observed. Parallelism between decrease of CH acceptance by HDL, oxidability of HDL and of total plasma testifies on weakness not only of CH-accepting, but also of antioxidant HDL functions in IHD patients.

[Effects of T-activin on the course of ischemic heart disease in cases of the development of sensitization to apoprotein B-containing lipoproteins]. / Vliianie T-aktivina na techenie ishemicheskoi bolezni serdtsa v sluchaiakh razvitiia sensibilizatsii k apoprotein-B-soderzhashchim lipoproteidam.

A comprehensive clinicoimmunological examination was made of 105 male patients aged 35-65 years who suffered from coronary heart disease. The authors identified a group of 33 patients whose unstable course of angina pectoris was associated with pronounced apolipoprotein B sensitization, as well as with the presence of the autoimmune lipoprotein-antibody complex and abnormalities in the cellular link of immunity. All 33 patients received antianginal agents. Out of them, 15 patients took additionally a course of T-activin therapy to modulate immunological shifts. The results of the examination demonstrated that the immunomodulator exerted a beneficial effect both on the course of CHD (reduction in the number of anginal episodes, improvement of left ventricular contractility) and the immune system (recovery of T-suppressor function, disappearance of lipoprotein sensitization, decrease in the patient's blood detection rates of the autoimmune lipoprotein-antibody complexes from 83 to 28%). The highest effect was reached by T-activin 1.5-2 months following termination of the course therapy. Immunomodulating therapy is regarded as an additional approach to the treatment of CHD patients with marked lipoprotein sensitization.

[Allele Frequency Analysis of Four Single Nucleotide Polymorphisms Locating in Promoter and 5'-Untranslated Regions of ABCAI Gene in Young Men - Survivors From Myocardial Infarction]. / Analiz chastoty vyiavleniia chetyrekh strukturnykh polimorfizmov DNK v promotornoi i 5'-netransliruemykh oblastiakh gena ABCA1 u muzhchin, perenesshikh infarkt miokarda v molodom vozraste.

Analysis of allele distribution of four single nucleotide polymorphisms (C-17G, C69T, G-191C and 319insG) of promoter and 5'-untranslated regions of the ABCA1 gene was carried out in a sample of 171 men, who had survived myocardial infarction before 45 years, and in controls. Two-fold increase of T69 and C-191 allele frequencies were observed in Russian population in comparison to Dutch one. While comparing allele and genotype distributions of the polymorphisms in the samples under study no statistically significant differences were found, so as no influence of different alleles on lipid spectrum data was observed. Role of polymorphisms under study appears to be insignificant in formation of genetic susceptibility to myocardial infarction in young men.

[Gene therapy of chronic infections of the urogenital system using cytotoxic peptides]. / Gennaia terapiia khronicheskikh infektsionnykh zabolevanii urogenital'nogo trakta s ispol'zovaniiem tsitotoksicheskikh peptidov.

Gene therapy of chronic infectious diseases of urogenital tract represents a new perspective field in the modern biological and medical sciences. In the review discuss one of the new directions in gene therapy of urogenital infections caused by Mycoplasma: inhibition of mycoplasmal infection after administration of recombinant plasmid vectors, expressed the genes of cytotoxic peptides.

[Correction of lipoprotein lipid peroxidation in experimental atherosclerosis with polyunsaturated fatty acids combined with antioxidants]. / Korrektsiia polinenasyshchennymi zhirnymi kislotami v komplekse s antioksidantami perekisnogo okisleniia lipoproteinov pri éksperimental'nom ateroskleroze.

Atherosclerotic lesion of the aorta and lipid peroxidation (LPO) in blood and in lipoproteins produced in hepatocytes were studied in rabbits with experimental atherosclerosis maintained on a diet enriched in polyunsaturated fatty acids containing in corn oil (2 ml/kg daily during 30 days) and antioxidants alpha-tocopherol and carnosine (2.5 mg/kg and 50 mg/kg, respectively, daily during 30 days). This diet exhibited a hypocholesterolemic effect accompanied by approximately a 10-fold decrease of the impaired aortic area, as well as lowered content of 2-thiobarbituric acid-positive LPO products occurring in blood and, especially, in apoB lipoproteins. The antioxidant-containing diet decreased distinctly the content of LPO products both in the liver tissue homogenate and lipoprotein fraction (d < 1.065 g/cm3) produced by hepatocytes during 30-min perfusion of liver tissue. The findings suggest that the diet enriched in polyunsaturated fatty acids and antioxidants contributed to a decrease of LPO products content in the blood serum and apoB lipoproteins as well as to the inhibition of lipoprotein oxidation during their synthesis in liver cells; the diet may be recommended for the prophylaxis and treatment of atherosclerosis.