[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).

[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.

Aldehydes and disturbance of carbohydrate metabolism: some consequences and possible approaches to its normalization.

There are many well-documented errors of metabolism involving genetic defects that affect carbohydrate utilization. The array of disorders includes the defective utilization of glucose, as well as enzymatic deficiencies in glycolysis and gluconeogenesis, and the pentose phosphate pathway. Besides, there is considerable literature about metabolic syndrome and diabetes. However, the main problem of their origin remains obscure. Also, it is presently beyond doubt that there are various causes of insulin resistance. The development of insulin resistance may be associated not only with insulin production disorders or presence of insulin antagonists but also with modification of the number of receptors and sensitivity of peripheral tissues. The insulin resistance originates from insulin signal transmission defects at its initial stages. It is presently uncertain which mechanisms of adaptation regulation are activated or should be activated under hyperglycemia conditions. This is the main problem of the selection of strategy of hyperglycemia treatment but it is important that aldehydes - the secondary products of lipid peroxidation and protein glycation (malondialdehyde and methylglyoxal) - make a contribution to abnormal metabolism. As far as the role of methylglyoxal in inhibition of antioxidant enzymes is concerned, the involvement of the ketoaldehyde in such processes as oxidative stress, cell proliferation control, and carbohydrate metabolism disorders does not cast any doubt.

Effects of chronic neuroticization on the monoaminergic systems of different structures in the brains of rats with different typological characteristics.

The levels of monoamines and their metabolites were studied by HPLC with electrochemical detection in homogenates of hypothalamus, hippocampus, prefrontal cortex, and amygdala in intact and neuroticized Wistar rats with different types of behavior in the open field and forced swimming tests. Intact rats with intermediate levels of activity and depressivity had higher serotonin concentrations in the hypothalamus and lower noradrenaline and hydroxyindoleacetic acid levels in the hippocampus than rats characterized by low activity and high depressivity. In neuroticization, the levels of study monoamines and their metabolites decreased in all the brain structures investigated with the exceptions of an increase in the dopamine concentration in the hippocampus and the dihydroxyphenylacetic acid concentration in the prefrontal cortex. The effect of neuroticization on the neurotransmitter systems in all study structures except the hypothalamus depended on the typological characteristics of the rats. This was most marked in rats with the extreme types of behavior--active and passive--in which changes in monoamine and metabolite contents were seen in all brain structures studied. Rats of the intermediate type showed no changes in any of the substances studied in the hippocampus.

Cumene peroxide and Fe(2+)-ascorbate-induced lipid peroxidation and effect of phosphoglucose isomerase.

Malondialdehyde (MDA) is one of cytotoxic aldehydes produced in cells as a result of lipid peroxidation and further MDA metabolism in cytoplasm is not known. In our experiments the liver fraction 10,000 g containing phosphoglucose isomerase and enzymes of the glyoxalase system was used and obtained experimental data shows that in this fraction there is an aggregate of reactions taking place both in membranes (lipid peroxidation) and outside membranes. MDA accumulation is relatively slow because MDA is a substrate of aldehyde isomerase (MDA <--> methylglyoxal). The well known enzyme phosphoglucose isomerase acts as an aldehyde isomerase (Michaelis constant for this enzyme Km = 133 +/- 8 microM). MDA conversion to methylglyoxal and further to neutral product D-lactate (with GSH as a cofactor) occurs in cytoplasm and D-lactate should be regarded as the end product of two different parametabolic reactions: lipid peroxidation or protein glycation.

A new role of phosphoglucose isomerase. Involvement of the glycolytic enzyme in aldehyde metabolism.

Lipid peroxidation in biological membranes is accompanied by malonic dialdehyde (MDA) formation, but the problem of its further metabolism in cytoplasm remains unsolved. The experimental data obtained in this work showed that the liver fraction prepared by centrifugation at 10,000g contained phosphoglucose isomerase and enzymes of the glyoxalase system. In this fraction in the presence of GSH there is an aggregate of reactions taking place both in membranes (lipid peroxidation) and outside membranes (MDA conversion to methylglyoxal and further to neutral D-lactate). This means that MDA is slowly accumulated because it is a substrate of aldehyde isomerase (MDA <--> methylglyoxal). Most probably, phosphoglucose isomerase serves as this enzyme. We concluded that D-lactate should be regarded as the end product of two different parametabolic reactions: lipid peroxidation or protein glycation.

[The influence of chronic neurotization on the monoaminergic systems of various brain structures in rats with various typological characteristics].

Typological behavioral features of Wistar rats were tested in the open field and in Porsolt test. Rats were assigned to groups with high (HAct), medium (MAct), and low (LAct) behavioral activities. The same rats were assigned to high (HDep), medium (MDep) and low depressive (LDep) groups. The release of norepinephrine, dopamine, serotonin and their metabolites in homogenates obtained from the hypothalamus, hippocampus, frontal cortex and amygdala was assessed by microdialysis and HPLC. In these groups, the monoamine concentrations were different: the level of serotonin was higher in the hypothalamus and norepinephrine and 5-HIAA levels were lower in the hippocampus of MAct - MDep rats as compared to LAct - HDep. Chronic neurotization caused changes in monoamine concentrations in the hypothalamus and amygdala in rats of all groups, whereas in the hippocampus and frontal cortex monoamine changes were observed in HAct - LDep and LAct -HDep rats. The most prominent changes in monoamines levels in neurotized rats with different types of behavior were found in the frontal cortex, amygdala and hippocampus. The results show a correlation between the typological of behavioral characteristics and the reaction to stress of monoaminergic systems of the hypothalamus, hippocampus, frontal cortex and amygdala.

[Markers of inflammation, autoantibodies to neurospecific antigens and outcome in patients with acute ischemic stroke]. / Markery vospaleniia, autoantitela k neirospetsificheskim antigenam i kharakter iskhoda u bol'nykh s ostrym ishemicheskim insul'tom.

To identify biochemical markers for carotid stroke outcome, blood serum levels of inflammation markers (C-reactive protein, orosomucoid, soluble p-selectin) and autoantibodies (AAB) to neurospecific antigens (glial fibrillary acidic protein, neuron specific enolase, S-100 protein) were studied in 27 patients (mean age 64 +/- 6 years) with acute ischemic stroke in inner carotid artery system on day 1-2 and 21 of the disease onset. To day 21, patients with good rehabilitation of neurological functions (group 1) demonstrated a decrease of C-reactive protein and soluble p-selectin concentrations, and unfavorable disease course was associated with a significant (p<0.05) increase of concentrations of these indices. On day 1 and 7, a level of AAT to glial fibrillary acidic protein was higher (p<0.05) in group 1 than in that with minimal rehabilitation and to day 21 it decreased relatively the baseline level. At the same time, patients with minimal rehabilitation had a stable AAT level. On day 7, the AAT level correlated with expression of neurological deficit on day 21 (r=0.510; p=0.019). No stroke-course-dependent differences were found in dynamics of orosomucoid as well as of AAT to neuron specific enolase and S-100 protein levels.

[Comparative study of hemodynamic effects of antidepressants (tetrindole and desipramine) during immobilization stress in hypertensive rats]. / Sravnitel'noe izuchenie gemodinamicheskikh éffektov antidepressantov (tetrindola i dezipramina) pri immobilizatsionnom stresse u gipertenzivnykh krys.

Tetrindole (a tetracyclic antidepressant, reversible MAO inhibitor of the A type) and desipramine (a tricyclic antidepressant, nonselective inhibitor of the reverse catecholamine trapping) produce opposite hemodynamic effects in stroke-prone hypertensive rats (SHR-SP): tetrindole reduced, whereas desipramine increased, the heart rate and arterial pressure. Under the acute immobilization stress conditions in SHR-SP, tetrindole inhibited development of the post-stressor tachycardia, while desipramine did not change the heart rate and increased the arterial pressure.

Hemodynamic effects of tetrindol in alert normotensive mice and rats after blockade of nitric oxide synthesis.

Single intravenous injection of antidepressant tetrindol (1 and 10 mg/kg), a reversible monoamine oxidase A inhibitor, dose-dependently decreased heart rate and mean arterial pressure (in a concentration of 10 mg/kg) in alert NMRI mice and Sprague-Dawley rats. Nitric oxide synthase blockade with L-NAME attenuated tetrindol-induced bradycardia in rats and completely abolished this effect in mice.

[Systemic and regional hemodynamics in alert rats with increasing hyperthermia]. / Sistemnaia i regionarnaia gemodinamika u bodrstvuiushchikh krys v usloviiakh narastaiushchei gipertermii.

The changes in the parameters of systemic and regional hemodynamics during thermal stress were followed up in awake male Wistar rats. The cardiac output (CO) and blood flow in 16 zones of the body were measured by means of 15 microns microspheres labeled by 4 different isotopes. The blood flow increased in the skin of the tail, the liver, heart, adrenals, and skeletal muscles and reduced in the organs of the splanchnic region and kidneys. When body temperature reached 42 degrees C the CO decreased. The shifts in the regional blood flow maintained their direction, with the exception of a sharp increase of blood flow in the small intestine which preceded or coincided with the beginning of a fall in arterial pressure. The rate of increase of left ventricular pressure remained at a high level. It is assumed that the disruption of celiac vasoconstriction is among the earlier developing links of hemodynamic disorders in thermal affections and is caused by the vasodilative effect of the factors of local control of the vascular functions.

[Hemodynamic mechanisms of the hypotensive effect of cobalt in anesthetized rats]. / Gemodinamicheskie mekhanizmy gipotenzivnogo deistviia kobal'ta u narkotizirovannykh krys.

Hemodynamic mechanisms of Co(2+)-evoked hypotension were studied in pentobarbital--anesthetised male Wistar rats. Bolus i.v. administration of cobalt sulphate (30, 90 and 270 mg/kg of Co) evoked dose-dependent hypotension followed by tachycardia and increase in left ventricular contractility index (dP/dt/P). Administration of beta-adrenoblocker propranolol (2 mg/kg) attenuated Co evoked (270 ug/kg) tachycardia and unmasked its cardiodepressive effects (dP/dt/P decreased by 11% and end-diastolic pressure increased by 55%). Cardiodepressive Co2+ effects were prevented by administration of verapamil (0.4 mg/kg). In the second group hemodynamic mechanisms of Co-evoked hypotension were studied with radioactive microspheres. Co2+ infusion (55 mg/kg) lowered blood pressure (in average by -11%) by decreasing total peripheral resistance (-25%). Cardiotoxic effects were obtained with a ++larger dose 80 mg/kg/min. It is concluded that Co decreased blood pressure by vasodilatator action and its cardiotoxic effects attenuated by sympathetic counterregulation and may be prevented by verapamil.

[Differences in the redistribution of cardiac output during hyperthermia in waking rats and guinea pigs]. / Razlichiia v pereraspredelenii serdechnogo vybrosa pri gipertermii u bodrstvuiushchikh krys i morskikh svinok.

The heat stress induced common responses in rats and guinea pigs: an increase in the blood flow at the sites of heat radiation and in the diaphragm, and its decrease in splanchnic area's organs and in kidneys while cardiac output remained constant. The species differences occurred in the responses of intestine and skeletal muscles' vessels. The differences seem to be due mainly to the differences in behavioral responses to the heat stress in these animals.

[Changes in the systemic and regional hemodynamics, hydration and engorgement of the lungs during occlusion of the thoracic aorta]. / Izmeneniia sistemnoi i regionarnoi gemodinamiki, ovodneniia i krovenapolneniia legkikh pri okkliuzii aorty v grudnom otdele.

The occlusion of the rat aorta's thoracic portion induces within 30 min hemodynamic shifts in major and minor circulation typical for a hypertensive incident. The occurring 4-5-fold increase of the lung venous pressure leads to no regular lung oedema and is of no major importance for its pathogenesis.