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The adult rats received both neurotoxin 6-hidroxidophamine and neurotoxin and melatonin. It was investigated a link between the disturbances of the brain antioxidant enzymes activity and thymic endocrine function, as possible pathogenic factors of parkinsonism, with changes in the number of neural stem cells (NSC) in the bulbus olfactorius. Rats with motor asymmetry in the apomorphine test and significant damage of the dopaminergic neurons in the-substantia nigra have decreased levels of superoxide dismutase, catalase and glutathione peroxidase activities in striatum (1.3-1.4 times) and blood thymulin content (8 times) compared to control group. On the contrary, examined indices were not changed in rats without motor asymmetry and correspondingly partly damaged neurons. The number of nestin(+)-cells in the bulbus olfactorius of rats without motor asymmetry increased from 91.2% to 99.3% and remained unchanged after melatonin administration course (10 mg/kg during 18 days). Melatonin administration resulted in the decrease in the number of nestin(+)-cells along with significant elevation of the decreased antioxidant enzymes activity and blood thymulin content in rats with circulatory movements. Possibilities of the enhancement of NSC differentiation in bulbus olfactorius into neuronal direction in such animals has been discussed. The conclusion about the potential use of melatonin as a neuroprotector in parkinsonism therapy has been made.

Physiological conditions of formation and subsequent lysis of thrombus were reconstituted in vitro in our research. Thrombus formation was initiated either by addition of exogenous thrombin or by contact of blood with anionic surface, which stimulates spontaneous coagulation of blood. Tissue plasminogen activator and/or protein C were previously added in the blood sample. The time of the beginning and total degradation of formed thrombi as well as the level of PC in lysates was controlled then. Only an addition of protein C alone or in combination with tissue plasminogen activator led to the most effective lysis of thrombi: their residual weight was 18% and 5% comparing to control. Addition of exogenous tissue plasminogen activator alone or in combination with protein C caused a 83% and 74% decrease of PC level in lysates of spontaneously formed thrombi, and 72% and 56% decrease for thrombi formed by thrombin, respectively. Without an addition of tissue plasminogen activator protein C level in lysates of thrombi formed by thrombin was 54% down on spontaneously formed thrombi. Thus, changes of PC concentration in isolated volume of clot seem to be controlled by thrombin at the stage of thrombus formation and by fibrinolytic system at the stage of fibrinolysis. Concentration of PC in lysates from clots formed by exogenous thrombin was decreasing over the next 10 hours of thrombolysis, which can also be the evidence of the interaction between the fibrinolytic and PC activation systems. A hypothesis is. formulated about an existence of endothelium-independent mechanism of PC activation in blood plasma with blood cells participation, which effectiveness increases in the process of thrombolysis.

NADPH-oxidase (NOX) is a novel transmembrane enzyme that appears to have pivotal role in the control of platelet signal pathways. The NOX activity in platelets is controlled by agonist receptors activation, which, in turn are modulated by NOX. This review focuses on participation of NOX in autocrine and paracrine regulation of platelet activation, aggregation secretion, protein synthesis and cell recruitment processes during thrombus formation. Possible involving of NOX in the cell-to-cell communication and coordination in response to trombogenic stimulus is discussed.

The changes of functional state isolated by Lanhendorf old rat hearts with low content of ubiqinone--coenzyme Q (CoQ) under activation of it endogenous synthesis through administration of precursors--4-hydroxybenzoic acid, methionine and modulator vitamin E were studied. The activation of ubiqinone biosynthesis contribute to cardioprotective effect due to reduce the degree of the ischemia-reperfusion injury in old rat heart, namely the restoration of myocardial contractile function and coronary flow as well as decrease the end diastolic pressure and oxygen cost of the heart compared with control group of the animals during ischemia-reperfusion. Thus the results allow to conclude that the activation of KoQ biosynthesis under administration of it precursors has protective effect in the development of the heart postreperfusion damages in aging.

We studied the sensitivity of mitochondrial permeability transition pore (MPTP) opening to natural inductors--Ca2+ ions in the rat heart mitochondria with chronic deficiency of nigrostriatal dopamine caused by an injection of selective neurotoxin 6-hydroxidofamine in an ascending lateral bundle of the forebrain. MPTP-opening was determined specrophotometrically (lamda=520 nm) by a decrease in an optical density resulting from mitochondrial swelling. It has been shown that the rat heart mitochondria with chronic deficiency of nigrostriatal dopamine are more sensitive to Ca2+ in its physiological concentration (10(-7) mol/l) and overload (10(-6) - 10(-4) mol/l) in comparison to control animals. Thus, obtained results lead to a conclusion that an increased sensitivity of the mitochondrial permeability transition pore to calcium and mitochondrial membrane permeability may be one of the causes previously reported of disturbance in contractile function of the rat heart with chronic deficiency of nigrostriatal dopamine.

The physiological significance of cardiac mitochondrial reactive oxygen species (ROS) regulation is unknown. In the current study, mitochondrial ROS (O2- and OH) generation, stable H2O2 and lipids peroxidation marker (malonic dialdehyde, MDA) pools, as well as pools of potent antioxidants--urea and uric acid--were determined in rat heart, miocardial mitochondria and in blood plasma and erytrocytes at low (44%) and high (96%) levels of cerebral dopamine-synthesis neurons destruction (by 6-hydroxidopamine treatment). In the untreated rats, ROS generation, H2O2 and MDA levels were low but in rats with chronic (3-4 month) deficiency of cerebral dopamine synthesis by nigro-striatal dopaminergic system, ROS generation and lipids peroxidation were progressively increased. Dopamine deficiency can improve mitochondrial efficiency of oxidative phosphorylation due to oxidative stress.

We studied the influence of antioxidants (trolox, melatonin and coenzyme Q10) on 6-hydroxydopamine-induced degeneration in the substantia nigra dopaminergic neurons from the left brain hemisphere. In rats, the level of unilateral degeneration of nigrostriatal dopaminergic system was estimated on the base of an intensity of rotation movements which were contralateral to denervated hemishere and resulted from systemic injections of a dopamine receptor agonist apomorphine. It has been shown that all tested antioxidants reduced a number of animals with apomorphine-induced behavioral asymmetry in a different degree: coenzyme Q10 reduced it twofold, trolox - fivefold and melatonin - sevenfold. We suggest that a neuroprotective effects of trolox, melatonin and coenzyme Q10 are associated with their ability to block the mitochondrial pore openings in the nervous cells under exploration, and this is the way to prevent apoptotic death. An oxidative stress has been proved to take part in the apoptosis in dopamine-producing neurons in the substantia nigra, and tested antioxidants have been shown to be effective in preventing neurodegeneration.