[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.

[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.

[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.

[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.

Principles and methods of medicamentous protection of myocardial cellular membranes for prevention of cardiac reperfusion syndrome.

A model of regional transitory coronary insufficiency was employed in experiments on 300 male albino rats under urethan anaesthesia (13.4 mmol/kg b.m.). The periods of myocardial ischaemia lasted 10, 40 and 120 min, followed by reperfusion lasting 40 min. The alteration of cellular membrane apparatus proved to be one of the most important mechanisms responsible for myocardial lesion during transitory coronarogenic ischaemia and for the development of cardiac reperfusion syndrome. The damage to cardiomyocyte membrane and intensity of reperfusion syndrome can be substantially reduced by using the following measures: inhibition of lipoperoxidation by antioxidative preparations, esp. myofedrin and verapamil; suppression of the intensity of phospholipase reactions activated by Ca2+; reduction of calcium ion accumulation in cardiomyocytes by substances lowering intracellular calcium content, esp. by verapamil.

[Sympathetic and parasympathetic regulation of the heart in transitory coronary insufficiency]. / Simpaticheskaia i parasimpaticheskaia reguliatsiia serdtsa pri tranzitornoi koronarnoi nedostatochnosti.

Experiments were made on 480 rats and 60 rabbits with transitory insufficiency (duration of myocardial ischemia 10.40 and 120 min the length of subsequent reperfusion 40-60 min). It was discovered that there was natural development of the phenomenon of limitation of drawing the heart in direct and reflectory reactions of the circulation system within the increase of duration of local ischemia and the beginning of the subsequent reperfusion. The phenomenon of "limitation", which is realized with the involvement of sympathetic and parasympathetic mechanisms, promotes a decrease of the extent of heart alteration during its local ischemia and increase of reparative process in the heart at the reperfusion period.

[Fibrinolytic activity of rat blood during transient coronary insufficiency]. / Fibrinoliticheskaia aktivnost' krovi krys pri tranzitornoi koronarnoi nedostatochnosti.

Local 10-min and 40-min myocardial ischemia was accompanied by a significant depression in the rat blood fibrinolytic activity. During 40-min postischemic myocardial reperfusion after short-term (10-min) myocardial ischemia fibrinolytic reactions were activated and after prolonged (40-min) myocardial ischemia they were suppressed.

[Reperfusion damages to the heart in acute transitory coronary failure and their prevention with myophedrin]. / Reperfuzionnye povrezhdeniia serdtsa pri ostroi tranzitornoi koronarnoi nedostatochnosti i ikh preduprezhdenie miofedrinom.

Experiments were made on 56 white noninbred male rats with transitory coronary insufficiency (duration of myocardial ischemia 10, 40 and 120 min, the length of subsequent reperfusion 10 and 40 min). It was discovered that there were changes in the ultrastructure of cardiocytes and vessels of the microcirculatory bed both in the area of ischemia and reperfusion and in the distant heart regions, an increase in myocardial cell and microvessel lesions during postischemic reperfusion not only in the area of ischemia but also in distant zones. In addition, a reduction was noted in the degree of ischemic and reperfusion myocardial injury during the prophylactic use of myophedrine. The mechanisms of the protective action of myophedrine in acute transitory coronary insufficiency are discussed.

[Changes in the activity of antioxidant enzymes in ischemia and subsequent reperfusion of the myocardium]. / Izmenenie aktivnosti "antioksidantnykh" fermentov pri ishemii i posleduiushchei reperfuzii miokarda.

Transitory coronary failure of the myocardium was accompanied by a considerable reduction in the activity of superoxide dismutase, glutathione peroxidase and glutathione transferase, with the activity of the enzymes under study being not different in the ischemized and distant from ischemia zones of the myocardium. Reperfusion did influence the activity of superoxide dismutase and glutathione peroxidase after 10 and 40 minutes of ischemia, whereas following 120 minutes of ischemia the activity of superoxide dismutase ascended after 10 and 40 minutes of reperfusion while the activity of glutathione peroxidase remained unchanged.

[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.

[Effect of different combinations of exogenous higher fatty acids on cardiac function during coronary ischemia and reperfusion]. / Vliianie razlichnykh kombinatsii ékzogennykh vysshikh zhirnykh kislot na funktsiiu serdtsa pri ego koronarogennoi ishemii i reperfuzii.

Experiments on 77 white random-bred male rats weighing 200 +/- 10 g have shown that combinations of high unsaturated fatty acids (HUFA) containing the precursors of prostaglandin synthesis, arachidonic and linoleic acids, produce a powerful antiarrhythmic action during transitory coronary insufficiency. The effect was seen not only during ischemia but also during subsequent myocardial reperfusion. The combination of HUFA containing arachidonic and linoleic acids as precursors of prostaglandin synthesis exerted a more demonstrable antiarrhythmic action than that without arachidonic acid. The degree of the ischemia-induced depression of contractile process was less versus control, provided HUFA combinations contained arachidonic acid.

[Dynamics of the cAMP and cGMP content of the heart in transient coronary insufficiency in rats]. / Dinamika soderzhaniia tsAMF i tsGMF v serdtse pri tranzitornoi koronarnoi nedostatochnosti u krys.

Experiments made on 127 white random-bred male rats weighing 200 +/- 10 g with transitory coronary insufficiency (TCI) with varying duration of myocardial ischemia (MI) have revealed consistent changes in the heart cAMP and cGMP. During MI, there was a biphasic variation in the concentration of cyclic nucleotides: an initial appreciable increase in the concentration was replaced by its lowering. At the same time the time course of cGMP content was more mobile in nature as compared to cAMP Reperfusion made at an early period (within the first 40 min) did not normally bring about the normalization of heart content of cyclic nucleotides whose concentration time course depended on the duration of the preceding MI. The pattern of changes in the concentration of cyclic nucleotides in the heart in TCI correlated to a significant degree with the previously described time course of the activity of the sympath- and cholinergic mechanisms by which heart work, contractile function and rhythm are controlled during TCI.