[Changes of human immunophenotype during adaptation to environmental factors, in different forms of pathology and their specific treatment].

The aim of the study was to elucidate mechanisms underlying variations of human immune phenotype in the course of adaptation to environmental factors, development of different forms of pathology and their specific treatment from dynamics of expression of surface CD-molecules in lymphocyte plasmolemma and immunoglobulin A, M, G levels in blood plasma. 253 assumingly healthy volunteers residing in the Moscow Megapolis exhibited a tendency toward enhanced lymphocyte apoptosis and reduced efficiency of their co-stimulation and cooperative interaction. Pathologies of different etiology were associated with the imbalance of specific and non-specific reactions of immune and biological control. Specifically, expression of CD 95 (Fas/APO-1) molecules triggering apoptosis increased in all patients with postmenopausal osteoporosis, pneumonia, and bronchial asthma but decreased in patients with rheumatic fever, erosive and ulcerative lesions in the digestive tract. Expression of surface receptors by the cells involved in "processing" of unshared antigens, their presentation by T-lymphocytes, inactivation and destruction of pathogens was enhanced only in patients with erosive and ulcerative lesions in the digestive tract. It decreased in rheumatic fever, postmenopausal osteoporosis, pneumonia, and bronchial asthma. Effective specific treatment leading to the normalization of (or tending to normalize) expression of CD molecules in lymphocytes and prevented changes in the immune and biological control system.

[Free radical processes in patients with iron deficiency anemia treated with iron medication].

AIM: To study the effects of iron salts drugs (ISD) sorbifer durules and ferro-folgamma on free radical processes in 44 patients with iron deficiency anemia (IDA). MATERIAL AND METHODS: IDA was diagnosed as a rule in women with uterine myomas, endometriosis, dysfunctional hemorrhage and other menorragias. Generation of active oxygen forms (AOF) was estimated by hemoluminescence (CL) before and after therapy. Lipid peroxidation was assessed by malonic dialdehyde (MDA) in plasma, antiperoxide plasma activity (APA)--by CL intensity in interaction with nitric peroxide. The system of antioxidant defense in ISD treatment was estimated by the activity of key antioxidant enzymes: superoxidedismutase, glutathion peroxidase and catalase. RESULTS: The studied ISD normalized hemoglobin 3-4 weeks after the treatment onset. MDA decreased. Generation of AOF and activity of plasmic antioxidant enzymes did not change much. CONCLUSION: ISD modulate free radical processes without oxidant stress.

[Free radical peroxidation processes and cardiotoxicity in treatment of malignant lymphomas].

The dynamics of free radical and peroxidation processes in patients with non-Hodgkin lymphomas (NHL) was studied parallel to the evaluation of changes in the functional condition of the cardiovascular system during a course of chemotherapy. Thirty-one patients (17 men; 14 women) aged 30 to 81, were examined. The dynamics of active oxygen forms (AOF) generation was studied using chemiluminiscent technique. The intensity of leucocyte chemiluminiscence (CL) (basal and zimozan-stimulated ones), the blood level of malonic dialdehyde, the antiperoxidation blood plasma activity according to its hydrogen peroxide-induced CL intensity, were measured. The functional condition of the cardiovascular system was evaluated using ECG, EchoCG, and Holter monitoring. The study revealed an increase in AOF generation by leucocytes, which correlated with the severity of the disease. The treatment of the NHL patients with cytostatics was associated with the activation of free radical reactions, which was maximal during the first 24 hours 1 hour after drug administration. Cytostatic therapy was characterized by a cardiotoxic effect, which consisted in an increase in the rate of various arrhythmias and a decrease in the heart contractility. The study demonstrates a direct correlation between the degree of AOF generation growth and the prominence of myocardial lesion signs. The authors conclude that the intensification of free radical reactions under the conditions of cytostatic therapy causes cardiotoxic effects, which requires a course of preventive cardioprotective therapy before chemotherapy is commenced.

[Mechanisms of disordered cardiac energy supply in transient coronary insufficiency]. / Mekhanizmy narusheniia énergeticheskogo obespecheniia serdtsa pri tranzitornoi koronarnoi nedostatochnosti.

Experiments conducted on 240 albino non-inbred male rats, using models of transitory coronary insufficiency of various duration (the period of myocardial ischemia lasted 10, 40 and 120 min), showed impaired energy supply to the heart in both periods of its ischemia and reperfusion in relation to three principal stages; first the synthesis of ATP, then the transportation and utilization of its energy. The period of ischemia was associated with disorders of predominantly the ATP synthesis and to a lesser degree of the transport and utilization of its energy. In the period of the post-infarction resumption of the coronary blood flow mostly affected were the mechanisms of the transportation and absorption of ATP energy by the effector apparatus of cardiomyocytes. At the early stage of myocardial reperfusion after a prolonged (40 and 120 min) local ischemia, the heart was damaged to a greater degree than in continuing ischemia of the same duration. The development of transitory coronary insufficiency following the preliminary administration of the antihypoxant gutimin is characterized by less marked disorders in the process of cardiac energy supply both in the period of myocardial ischemia and at the early stage of the reperfusion.

[Cardiac function in transient coronary insufficiency after electrophoretic and injection methods of obsidan administration]. / Funktsiia serdtsa pri tranzitornoi koronarnoi nedostatochnosti v usloviiakh elektroforeticheskogo i in'ektsionnogo metodov vvedeniia obzidana.

The peculiarities of the preventive use of obsidan administered by injection and electrophoresis were studied in experiments on rats with a model of transitory coronary insufficiency. A high efficacy of obsidan was demonstrated irrespective of the route of its administration into the body. This was manifested by a decrease in the rate of cardiac contractions in intact animals and depression of hyperkinetic cardiac reaction in the initial period of myocardial ischemia. The unfavourable inotropic and the antiarrhythmic effects of the agent were less in electrophoretic administration than in injection.

[Use of the inhibition of myocardial lipid peroxidation for use therapy and prevention of experimental transitory coronary failure]. / Primenenie ingibirovaniia perekisnogo okisleniia lipidov miokarda dlia terapii i profilaktiki tranzitornoi koronarnoi nedostatochnosti v éksperimente.

This work was done on 116 white random-bred male rats using the experimental model of transient coronary insufficiency of varying duration and showed that activation of free-radical peroxidation of myocardial lipids is one of the main pathogenetic factors in the mechanism of development of the ischaemia and reperfusion damage of the heart in transient coronary insufficiency. Inhibition of lipid peroxidation after preliminary administration to the animals of sodium selenite and myophedrine significantly enhanced the heart's resistance to reversible ischaemia. It is suggested that the use of antioxidants is an effective method of pathogenetic therapy and prevention of transient coronary insufficiency.

[Antiarrhythmic effect and influence on myocardial contractile function of the preparation, mexitil]. / Antiarritmicheskii éffekt i vliianie na sokratitel'nuiu funktsiiu miokarda preparata meksitila.

Complex clinical instrumental examination of 30 patients with disorders of cardiac rhythm and experimental study on 49 albino rats with induced transitory coronary insufficiency of various duration which were then subjected to reperfusion showed that Mexitil is an effective anti-arrhythmic agent in the treatment of ventricular disorders of rhythm and that during long-term treatment wih it inotropic myocardial function diminishes insignificantly; treatment produced positive results in 73% of patients.

[Effect of molsidomine on cardiac function in experimental transitory coronary insufficiency]. / Vliianie mol'sidomina na funktsiiu serdtsa pri éksperimental'noi tranzitornoi koronarnoi nedostatochnosti.

Increased resistance of the heart to acute transitory coronary insufficiency under conditions of prophylactic use of molsidomin was demonstrated in experiments on dogs and rats. The agent prevents electric destabilization of the heart. Reduction of pre- and postexertion of the heart is one of the main factors of the protective action of molsidomin. It is suggested that the drug may be included in the complex of measures used in the treatment of patients suffering from anginal and anginal-arrhythmic forms of stable and unstable angina pectoris.

[Nephrogenic hypertension and carcinogenesis]. / Nefrogennaia gipertoniia i kantserogenez.

The results of studies conducted on 355 white nonpedigree male rats (268 experimental and 87 intact animals) indicated that nephrogenic hypertension: a) potentiates the development of benz(a) pyrene induced blastomas; b) enhances, as a rule, the growth of transplantable tumors: carcinoma RS-1 and sarcoma 45; c) results in a tendency to more frequent metastasization of the tumors (Walker carcinosarcoma and Zajdela ascites hepatoma).

[Vasaprostan treatment of fibrosing alveolitis in patients with pulmonary hypertension]. / Primenenie vazoprostana u bol'nykh legochnoi gipertoniei pri fibroziruiushchem al'veolite.

AIM: To study clinical efficacy of vasaprostan in patients with fibrosing alveolitis (FA) complicated by pulmonary hypertension (PH), its effect on functional activity of platelets and endothelium, intensity of free radical processes. MATERIAL AND METHODS: Seven FA patients were examined. They had either idiopathic FA or FA with diffuse diseases of the connective tissues. The following methods were used to assess the effect: standard clinical tests, high resolution computer tomography, Doppler echocardiography, definition of the complex thrombin-antithrombin (TAT) and thrombocytic factor 4 (TF-4). Generation of oxygen active forms by leukocytes was measured by luminol-dependent chemiluminescence. Morphological verification of the diagnosis was made by the results of open pulmonary biopsies. RESULTS: Vasaprostan reduced pressure in the pulmonary artery from 31.6 +/- 2.31 to 19.58 +/- 3.90 mm Hg (p < 0.05) and coagulation parameters. TAT decreased after 2 and 8 weeks of treatment from 15.25 +/- 4.5 to 5.1 +/- 0.33 and 2.4 +/- 0.31 pg/ml (p < 0.05). Initially low TF-4 (2.11 +/- 0.39 pg/ml) elevated to the end of the treatment and reached values close to control (4.37 +/- 0.25 pg/ml, p < 0.05). Moreover, vasaprostan enhanced the ability of platelets to inhibit generation of active oxygen forms (from 0.9 +/- 0.18 to 1.23 +/- 0.16 r. u., p < 0.05) and thus depressed activity of lipid peroxidation. CONCLUSION: Good effect of vasaprostan on platelet activity, free radical processes validates its use in combined treatment of various FA forms for correction of PH, its complications and as an antifibrogenic agent.

[Pathogenic and adaptive changes of the heart in regional myocardial ischemia and postischemic myocardial reperfusion]. / Patogennye i adaptivnye izmeneniia v serdtse pri ego regionarnoi ishemii i posleduiushchem vozobnovlenii koronarnogo krovotoka.

The evidence is presented and on development of both adaptive and pathogenic changes in the heart in its regional ischemia followed by renewal of circulation in major branches of coronary arteries. Cellular and molecular mechanisms of cardiac changes are characterized: energy supply to cardiomyocytes; their membrane physico-chemical status and structure, enzymes activity, ion-liquid balance, electrophysiological parameters; genetic program of myocardial cells; mechanisms of neurohumoral regulation. Mechanisms and role of the phenomenon of hormone-neuromediator dissociation of catecholamines (adrenaline and noradrenaline) correlations in long-term ischemia and reperfusion of the myocardium are described.

[Patterns and the role of changes in the sympathetic and parasympathetic regulation of the heart in local ischemia and reperfusion]. / Zakonomernosti i rol' izmenenii simpaticheskoi i parasimpaticheskoi reguliatsii serdtsa pri ego lokal'noi ishemii i reperfuzii.

Modelling of transient coronary insufficiency on 480 conscious and unconscious non-inbred albino mate rats during 10-, 40-, or 120-min coronary occlusion, followed by 40-60-min myocardial reperfusion revealed characteristic changes in the sympathetic and parasympathetic mechanisms of cardiac regulation. According to the extent and duration, 3 phenomena were identified, which were of mainly adaptive or pathogenic significance. These included: 1) replacement of the domination of sympathetic influences on the heart by the predomination of parasympathetic effects; 2) development of hormonal and neuromediator dissociation of catecholamine levels in the heart; 3) regulation-restricted cardiac participation in systemic hemodynamic responses. The predomination of adaptive effects of the above phenomena caused a reduction in the ischemic and reperfusion alteration of the heart and potentiated its reparative processes. With progression and more prolonged duration of these phenomena there is an additional myocardial regulatory alteration.

[Changes in generation of superoxide anion-radical by phagocytic and other cells of atherosclerotic plaques at different stages of human atherosclerosis]. / Dinamika generatsii superoksidnogo anion-radikala fagotsitiruiushchimi i drugimi kletkami ateroskleroticheskikh bliashek na raznykh stadiiakh aterogeneza u cheloveka.

We investigated changes in generation of free radicals of oxygen including superoxide anion-radical (SAR) of oxygen by phagocytes and other cells of atherosclerotic plaques resected in operations of aortofemoral or aortoiliac bypass grafting and plastic vascular surgery of 38 patients with obliterating atherosclerosis obliterans of the lower extremities. We found some regularities in changes of SAR generation by phagocyting cells of atherosclerotic plaques at different morphological stages of their formation. Generation of the radicals progressively increased at the stage of fibrous plaques (1.56 times vs control), increased still more at the stage of their atheromatous alterations (2.3 times) and noticeably decreased at the stage of their calcinosis. Simultaneously, there was intensification of SAR formation by non-phagocyting cells of atherosclerotic plaques under their stimulation by NADPH-H (in fibrous and atheromatous plaques 1.3 and 2.0 times, respectively). On the contrary, at calcinosis stage NADPH-stimulated radical generation by these cells reduced.