[Assessment of clinical-instrumental, morphological data and expression of coxsackie adenovirus receptor in patients with inflammatory cardiac pathology].

In 22 patients with heart failure and/or ventricular arrhythmias presumably of inflammatory etiology the results of clinical and instrumental investigation were analyzed and compared to the endomyocardial biopsy data. In the subgroup of patients with left bundle branch block (LBBB) we revealed features indicative of lesser contribution of inflammatory destruction in pathogenesis of cardiomyopathy. The only virus, detected in biopsy samples, was parvovirus B19. Its persistence in myocardium was not related to activity of inflammation and severity of clinical course. Increased expression of Coxsackie adenovirus receptor (CAR) was found in 20 patients. It was not related to inflammatory cells infiltration and virus persistence in myocardium. Patients with most prominent CAR expression were characteried by right heart dilatation, more severe heart failure and absence of LBBB. Enhancement of CAR expression could reflect the attempt of organism to repair intercellular communications between cardiomyocites and to protect cells from the products of necrotic lysis during long standing inflammation.

[The study of hypotensive action of dinitrosyl-iron complex with glutathione containing drug oxacom in healthy volunteers].

On the basis of earlier executed studies of hypotensive effect of dinitrosyl iron complexes (DNIC) with glutathione, the drug has been created in industrial conditions named oxacom. Preliminary pharmacological studies of oxacom have not revealed negative qualities. The drug has been now tested in 14 healthy men in whom at single intravenous introduction it caused typical response - a decrease of diastolic as well as systolic arterial pressure on 24-27 mmHg through 3-4 min with subsequent very slow restoration in 8-10 hours. The heart rate after initial rise was quickly normalized. Echocardiography revealed unaltered cardiac output in spite of reduced cardiac filling by 28%. The multilateral analysis of clinical and biochemical data has revealed an absence of essential alterations which could lead to pathological consequences. The drug is recommended for carrying out of the second phase of clinical trial. The comparative study of the efficiency of hypotensive action of oxacom, S-nitrosoglutathione (GS-NO) and sodium nitrite (NO2) in rats has shown that the duration of effect was the greatest at oxacom action.

[Dynamics of morphological structures of platelets in patients with ischemic heart disease in dependence on blood levels of fatty acids].

Levels of fatty acids in platelets of ischemic heart disease (IHD) patients (n = 39) has been compared with those in healthy subjects (n = 12). Increased content of arachidonic acid and thromboxane A2 in platelets of IHD patients forms thrombogenic picture of IHD. High level of fibrinogen and decrease in heparin and antithrombin III in IHD patients facilitates formation of blood clots. Morphological examination of platelets in IHD patients has demonstrated an increase of levels of discocytes and spherocytes as well as appearance of small and large platelet-erythrocyte aggregates promoting blood slot formation.

[Neurospecific proteins and autoantibodies in serum of patients with acute ischemic stroke].

Neurospecific enolase (NSE), gliofibrillar acid protein (GFAP), S100 protein and autoantibodies (AAB) to these proteins have been measured in the blood of 42 patients with acute ischemic stroke. Concentrations of all parameters we re increased in patients compared to the control group. There were a positive correlations between contents of AAB to GFAP and AAB to NSE (r = 0.470; p < 0.015) and a reverse correlation between concentrations of NSE and AAT to NSE (r = -0.301; p < 0.028). A study of the relationship between intensity of neurological deficit and AAB concentrations revealed the reverse correlation between the level of AAB to GFAP and scores on the European Stroke scale (ESS) (r = -0.509; p < 0.009) at the first day of ischemic stroke, i.e. in patients with marked neurological deficit (low scores on ESS) the levels of AAB to GFAP were higher. The higher concentration of AAB to NSE was found for the satisfactory rehabilitation, while the neurological deficit was significantly more severe (p = 0.034) at the AAT to NSE level less than 1.19 relative units. The more complete rehabilitation to the 21st day was reverse-correlated to the NSE concentration (r = -0.309; p < 0.026). There was the positive correlation between the restoration of lost functions (the increase of ESS scores from the 1st to 21st days) and levels of AAB to GFAP (r = 0.505; p < 0.023) and AAB to S100 (r = 0.450; p < 0.046).

[Disturbances of primary hemostasis in patients with dilation cardiomyopathy].

We studied morphological characteristics of platelets and parameters of platelet aggregation in patients with dilation cardiomyopathy. Augmented aggregatory activity of platelets was found in 76% of patients. In blood of majority of patients we found circulating leukocyte-platelet aggregates. This evidenced for development of inflammatory process and could be related to disturbances of blood rheology. In 2 patients examined by virusological method we revealed presence of a virus inside platelets. This phenomenon might serve as one of possible pathological pathways of disease progression at the account of spread of viral infection along vascular bed during thrombus formation.

[Difficulties in evaluating the efficacy of antiplatelet therapy in clinical practice].

AIM: To evaluate platelet activity changes in patients with coronary artery disease (CAD) treated with aspirin, clopidogrel and combination of these drugs; to estimate the rate of resistance of CAD patients to antiplatelet treatment. MATERIAL AND METHODS: 199 patients with stable CAD were included in the study. Of them, 83 were given aspirin, 46 received clopidogrel, 34--double antiplatelet therapy (both aspirin and clopidogrel). The trial also studied an additional group of 18 CAD patients on double antiplatelet therapy who had hemorrhages. The control group consisted of 25 healthy volunteers. Platelet aggregation was measured both by a mean size of aggregates (MSA) and light transmission (LTM, Born method) using BIOLA platelet aggregation analyzer. A platelet shape, leukocyte-platelet aggregates (LPA) and erythrocyte-platelet aggregates (EPA) in the whole blood were studied using scanning electron microscopy. The levels of IL-6 and sVCAM were also measured. RESULTS: It was found that 59.8% patients with CAD had high platelet reactivity revealed in 94.9% of cases by measuring spontaneous and induced by 0.1 mcM ADP platelet aggregation. LTM revealed increased platelet reactivity only in 10.7% patients. Resistance to aspirin correlated with the presence of LTA (r = 0.629, p = 0.0001) and the number of large "reticulated" platelets (r = 0.334, p = 0.001). Low platelet reactivity was associated with the presence of circulating EPA (r = -0.362, p = 0.008). Administration of clopidogrel did not decrease platelet reactivity to normal levels in 34.7% patients which correlated with the presence of LPA and EPA. In 83.3% patients with hemorrhages platelet aggregation, induced by 5.0 mcM, ADP was dramatically decreased. CONCLUSION: Resistance to antiplatelet therapy is related to platelet heterogeneity, the presence of inflammation and state of erythrocytes. LT is capable to reveal only a part of patients resistant to antiplatelet drugs. To fully identify these patients, it is necessary to register spontaneous platelet aggregation and aggregation induced by low doses of ADP. Redundant inhibition of platelet reactivity could be the cause of hemorrhagic events.

[Autoantibodies to glial fibrillary acid protein in patients with different forms of cerebral vascular pathology].

Autoantibodies to neurospecific proteins are currently reported to play a role in the development of organic brain damage. To study a diagnostic value of concentration of autoantibodies to glial fibrillary acid protein (AAB to GFAP), the latter was determined in the blood serum of patients with different forms of cerebral vascular damage. The 1st group included 22 patients with cerebral vascular insufficiency, stage II, the 2nd - 14 patients with ischemic heart disease without sings of cerebral damage and the 3rd - 27 patients with acute ischemic carotid stroke. A control group consisted of 35 healthy volunteers. AAB to GFAP level was determined using ELISA. The maximal concentration of AAB to GFAP was found in patients with stroke (2,27+/-0,30 mkg/ml) that was significantly higher compared to the controls (0,95+/-0,03 mkg/ml, p<0,05) and the 2nd group (0,95+/-0,04 mkg/ml, p<0,05). The AAB to GFAP concentration was higher (2,98+/-0,45 mkg/ml, p<0,05) in patients with favorable outcome of stroke than in those with fatal outcome or severe debilitation (1,29+/-0,08 mkg/ml, p<0,05). The data obtained show a correlation of AAB to GFAP concentration with character and severity of cerebral vascular pathology that allows to suggest their assessment as a predictive factor.

[Platelet activation and inflammation markers in patients with coronary heart disease and depression].

AIM: To study morphological features and functional activity of platelets, their relations with the level of inflammation markers in coronary heart disease (CHD) patients with depression. MATERIAL AND METHODS: The study group consisted of 33 CHD patients with stable effort angina (NY-HA FC I-III), 14 had depression, 19 were free of depression. Sixteen healthy volunteers comprised the control group. Platelet aggregation was registered by a mean size of aggregates and turbidometrically. Platelets shape, leukocytic-thrombocytic and erythrocytic-thrombocytic aggregates (LTA, ETA) in the whole blood were studied electron-microscopically. The levels of IL-2, IL-6, TNF-alpha, sVCAM, hsCRP were measured in the blood, serotonin--in platelets. RESULTS: Spontaneous aggregation enhanced in 52.6% CHD patients (p < 0.05). The blood contained reticular platelets, high number of prothrombocytes (p < 0.05), mean volume of thrombocytes was greater (p < 0.05). This reflected changes in megakaryocytopoiesis. Some of the patients had LTA and ETA. Out of inflammation markers, only IL-6 and sVCAM were elevated (p < 0.01), hsCRP concentration rose, but not above normal range. Serotonin in platelets was the same in the patients and controls. Depression aggravated the disorders and elevated other indices. Spontaneous aggregation was high in 71.4% of depressive CHD patients. The count of reticular platelets, prothrombocytes, mean volume platelets were also elevated. LTA and ETA were high in all the depressive patients. Elevated were also concentrations of IL-6, sVCAM, IL-2, hsCRP. Serotonin in platelets was low (p < 0.05). CONCLUSION: Depression stimulates functional activity of platelets, is a factor of risk of intravascular inflammation and contributes to development of thrombotic complications in CHD patients.

[A trial of long-term lovastatin treatment in patients with a heterozygous form of hereditary hypercholesterolemia]. / Opyt dlitel'nogo lecheniia lovastatinom bol'nykh s geterozigotnoi formoi nasledstvennoi giperkholesterinemii.

Patients with heterozygous family hypercholesterolemia (HFH) were divided into two groups. Group 1 patients received lovastatin in a daily dose 40-60-80 mg under control of lipids and peripheral blood biochemistry. In 17 patients lovastatin was given as monotherapy, in 15 patients it was combined with plasmapheresis. No hypolipidemic therapy was given to ten patients of group 2. The treatment and follow-up lasted for 4.1 +/- 1.9 years, on the average. A marked hypolipidemic effect was seen in the comorbid therapy. 43% of the patients became resistant to lovastatin, the resistance developed more frequently in monotherapy. The blood fibrinogen fell by 40%, spontaneous and induced platelet aggregation returned to normal, being somewhat higher in subjects resistant to lovastatin therapy. The study shows that hypolipidemic therapy has reduced the risk of IHD fatal complications and progression of non-coronary atherosclerosis in patients of group 1.

The morphological properties of the blood thrombocytes in bronchial asthma patients before and after thrombocytapheresis. / Morfologicheskie svoistva trombotsitov krovi u bol'nykh bronkhial'noi astmoi do i posle trombotsitafereza.

Morphological characteristics of platelets were assessed electron microscopically in 15 patients with atopic and aspirin bronchial asthma (BA) before and after thrombocytapheresis (TA). All the patients had a definite shift of platelet subpopulations to greater percentage of spherical forms as well as defects in cell ultrastructure. This makes evident platelet activation in patients with BA aggravation. TA entails a positive trend to normalization of platelet subpopulations and cytoskeleton. The ability to normalize platelet morphofunctional status determines its clinical effectiveness in bronchial asthma.

[Functional state of thrombocytes in Yersinia infection]. / Funktsional'noe sostoianie trombotsitov pri iersinioznoi infektsii.

As many as 94 patients with yersiniosis were examined for the morphofunctional status of platelets (aggregation, disaggregation, endo-exocytosis and platelet forms). The data indicate that platelet from patients with yersiniosis possess a high ability for aggregation and a low ability for disaggregation. According to the experimental and clinical data, emoxipine can restore disturbed function of human platelets.

[Morphofunctional characteristics of the bipolar forms of thrombocytes]. / Morfofunktsional'nye osobennosti bipoliarnykh form trombotsitov.

The formation and circulation of bipolar platelet forms in the vasculature have been first studied. All the transitional stages of platelet metamorphosis from disk-shaped to bipolar forms have been traced. The basic functions in bipolar platelets (adhesion and aggregation) were inhibited. Such cells were shown to appear in various pathologic conditions (pheochromocytoma, intravascular coagulation syndrome). Prazosin, alpha-blocker, was capable of inducing reverse metamorphosis accompanied by the recovery of platelet functional properties.

[Action of toxic staphylococcal (St. aureus) substances on the functional properties of the thrombocytes]. / Deistvie toksicheskikh substantsii stafilokokka (St. aureus) na funktsional'nye svoistva trombotsitov.

The effect of toxic substances from St. aureus on morphofunctional properties of platelets has been studied in vitro. The toxic substances have been shown to induce platelet aggregation and stimulate their secretion. The platelets are transformed from discs to spheres with small pseudopodia. It is believed that platelet aggregation and secretion play an essential role in hemostasis and microcirculation disturbances.

[Reversible endocytosis apparatus of the blood platelets]. / Apparat obratimogo éndotsitoza krovianykh plastinok.

The functioning of ganules of blood platelets participating in the reversible endocytosis reaction was investigated in rabbits. Eczocytosis was shown to be initiated by inducers of two types: proteolytic enzymes and compounds accumulated by the granules (biogenic amines, dyes, anesthetics and phenothiazines). Heparin inhibits thrombin-induced eczocytosis. During eczocytosis produced by accumulation of compounds by blood platelet granules, the cells lose their capacity for maintaining the aggregation state. The nature of blood platelet granules participating in the reversible endocytosis reaction is discussed.

[Lysosomes-like thrombocyte alpha-granules: the activation and inhibition of the release of the contents in blood coagulation]. / Lizosomopodobnye al'fa-granuly trombotsitov: aktivatsiia i ingibirovanie osvobozhdeniia soderzhimogo pri gemokoaguliatsii.

The mechanism of the release of alpha-granules constituents of thrombocytes was studied in the course of blood coagulation utilizing the fluorometric technique. The release reaction can be induced by proteolytic enzymes. The process is stimulated by the presence of extracellular Ca2+. This pattern of release reaction belongs to "release II" type. Aminazin can also induced release of alpha-granules constituents. Heparin inhibited release II induced by Ca2+ in citrated plasma, whereas streptase had no effect.