[Modern principles of epilepsy therapy].

Long regular use of antiepileptic drugs (AED) aimed at reducing frequency of seizures or stopping them completely without any significant side-effects is a main principle of epilepsy treatment. The main attention is drawn to the issues of tolerability of antiepileptic therapy and compliancy, mutual understanding between a physician and a patient as well as relatives and other significant persons. The timely detection and correction of side-effects is integral part of epilepsy treatment. Currently, the attention is focused on quality of life of patients with epilepsy including physical and mental health, education, social and psychological functioning. In some cases, the occurrence of rare seizures with minimal clinical presentation or even more frequent seizures which are not dangerous to a patient is less harmful than decreasing of quality of life due to the effect of larger AED number or dose. The balance between AED therapeutic and toxic effects is a main question in epilepsy therapy. Pharmacotherapy of epilepsy requires deep knowledge of AED: spectrum of therapeutic efficacy and extent of drug effect; safety, tolerability and side-effects, in particular severe and life-threatening ones, specifics of pharmacokinetics, pharmacodynamics, between-drug interactions and mechanisms of action; titration rate, necessity in laboratory tests during treatment, peculiarities of application of pharmacoeconomics. The present review addresses modern aspects of epilepsy therapy.

[Proteolytic processes in lung tissue of rat posterity after whole-body chronic irradiation with low doses].

Intensification of proteolytic processes accompanied by inhibited antiprotease activity in lung tissue of first generation posterity of rats irradiated with a total dose of 0.25 Gy (0.01 Gy per day) before gestation was shown. The obtained data satisfied to imbalance in functioning of regulation systems, tension of adaptation mechanisms with possible rapider reduction of adaptation resistance of broncho-lung system of irradiated parents' posterity. Vector changes in correlation of indexes in the proteinase-antiproteinase system were analogous in all experimental series (irradiated male x irradiated female, irradiated male x intact female, intact male x irradiated female) with maximal expression in the group obtained from parents both irradiated before gestation. It could be possible to propose a presence of non-stable genome in posterity of irradiated parents, that satisfied to role of genetic aspects in development of the late functional disorders.

[The biological effects of combined exposure to low-dose irradiation and heavy metal ions]. / Biologicheskie éffekty kombinirovannogo vozdeistviia nizkodozovogo oblucheniia i ionov tiazhelykh metallov.

It was shown that chronic 0.25 Gy irradiation of rats (0.01 Gy/day) at background of heavy metal penetration (Cu2+, 20 mg/l or Co2+, 5 mg/l) with drinking water had caused significant accumulation of the free-radical products proportional to exhausting antioxidant and oxidizing-reduction potential in various organs and tissues. Radiation was shown to be primary harmful factor for the brain, spleen, lungs, and blood plasma, whereas the liver and heart muscle were affected with chemicals at first. Under prolonged unfavourable influence the biochemical changes observed were sustainable and progressing that satisfied to transformation of protective-adaptive reactions into prepathology stage.

[Lipid peroxidation in the lungs upon inhalation exposure to low concentrations of lead salts]. / Peroksidnoe okislenie lipidov v legkikh pri ingalatsionnom vozdeistvii soli svintsa v nizkikh kontsentratiiakh.

Effects of inhalation with low concentration lead salts on lipid peroxidation intensity and antioxidative system state were investigated in respiratory pulmonary branch in rats after both short-term and chronic exposures to 0.01% Pb(CH3COO)2. It was shown that the short-term toxic action had considerably affected on the antioxidant system state in lungs as a result of tissue antioxidative activity exhausting. Under the chronic lead inhalation penetrating disorders in adaptive mechanisms were found. It was reflected in lipid peroxidation product accumulation and decreased parameters of antioxidant defense, and development of energy deficiency.

[The neuromediator modulation of the ionic composition of the brain cells in rats irradiated at nonlethal doses]. / Neiromediatornaia moduliatsiia ionnogo sostava kletok golovnogo mozga krys pri obluchenii v neletal'nykh dozakh.

It had been found that both the single prolonged irradiation and chronic (fractionated) one with doses of 25 and 50 cGy (1.75 mGy/min) caused essential modification of the biphase modulative effects of acetylcholine and gamma-aminobutyric acid upon K+ level in rat brain cortex slices to be compared to the acute lethal irradiation influence. The results of model experiments showed saturated fatty acids to be significant for the changes in regulative functions of nerve cell membranes after exposure to low dose-rate radiation.

[Pharmacological approaches to study of choline- and GABA-receptor sta tes in neuronal membranes after low doses irradiation]. / Farmakologicheskie podkhody k izucheniiu sostoianiia kholino- i GAMK- retseptorov neironal'nykh membran pri rentgenovskom obluchenii s maloi moshchnost'iu dozy.

As a result of the study of both the acetylcholine (10(-10) M; 10(-6) M) and gamma-aminobutyric acid (10(-9) M; 10(-5) M) effects on active K+ transport in rat brain cortex slices using any selective antagonists of cholinoreceptors (ChR) and GABA-receptors (GABA-R) it had been shown that after whole-body 25 cGy irradiation (1.75 mGy/min) metabotropic muscarinic ChR and GABAB-R were involved into processes of neurotransmitter modulation, whereas under the normal conditions they were mediated via ionotropic nicotinic ChR and GABAA-R. Observed changes were supposed to be an adaptive reaction. Perhaps, postirradiation structure-functional disorders in receptors were pointed as one of the reasons leading to essential changes in the interneuronal metabolic communication processes in CNS.

[Proteolytic system in lungs upon inhalation exposure to low doses of lead salts]. / Sistema proteoliza v legkikh pri ingaliatsionnom vozdeistvii soli svintsa v nizkikh kontsentratsiiakh.

Changes in proteinase--antiproteinase activities in lungs as a result of short-term (for 1 week) inhalation of rats with 0.01% (CH3COO)2 Pb have wholly compensative patterns, but it have been found increased cathepsine B activity as a negative prognostic factor. Chronic (for 2 month) toxicant inhalation caused considerable activation of both trypsine and cathepsine B under decreasing alpha 1-antitrypsine and alpha 2-macroglobuline activities. Cathepsine L activity was not affected. Disorders in the proteolysis system were evaluated as desadaptation situation in lung tissue under chronic toxic influence.

[Effect of beta-carotene oil and bee pollen on ion transport in rat brain slices following radiation-chemical exposure]. / Effekty beta-karotinovogo masla i pchelinoi obnozhki pri radiatsionno-khimicheskom vozdeistvii na ionnyi transport v srezakh mozga krys.

Chronic combined exposure to ionizing radiation with dose of 0.25 Gy and cadmium chloride or atrazine to be present in drinking water at five-fold Limited Permissible Concentration (LPC) values led to the additively reduced intercellular K+ level in rat brain, that was at first choice caused by the active ion transport disorders in the case of irradiation, and by the changes in membrane permeability in the case of toxic loading. Applying of beta-carotene oil and bee pollen both abolished radiation effects, but no chemical toxicant ones. Authors supposed the selective action of the observed drugs to be connected with antioxidant activities of them.

[Role of GABA in the modulation of Na, K-pump activity in nerve cells after irradiation and experimental modification of membrane lipid component]. / Rol' GAMK v moduliatsii aktivnosti Na, K-nasosa nervnykh kletok pri obluchenii i éksperimental'noi modifikatsii lipidnoi komponenty membran.

After irradiation acute (12 Gy, 600 mGy/min), single prolonged (0.25 Gy, 1.75 mG/min), chronic (0.01 Gy/day, 0.25 Gy, 0.50 Gy, 1.75 mGy/min), and experimental disturbances of cell membranes with phospholipases-A2, -D, and arachidonic acid administration the considerable changes in Na,K-pump function were found in rat brain cortex slices, with their reduction almost to the control level in presence of gamma-aminobutyric acid (0.1-10.0 mcM). It had been supposed existing of the GABA-ergic "homeostasis control" mechanism, which restores the intracellular potassium homeostasis via GABA-modulation of the Na,K-pump activity by principles of receptor-mediated structural-membrane regulation under extreme factor influence.

[The postradiation effect of acetylcholine and GABA on the active potassium uptake by slices of rat cerebral cortex]. / Postradiatsionnyi éffekt atsetilkholina i GAMK na aktivnyi zakhvat kaliia srezami kory golovnogo mozga krys.

Whole-body X irradiation (0.155 and 0.310 C/kg) was shown to modify the biphase effect of acetylcholine and GABA on antigradient K+ uptake by rat brain sections. Radiation made the effects of neuromediators on active K+ transport be differently directed: acetylcholine enhanced the inhibitory effect of radiation and GABA restored the Na-K-pump function.

[Postradiation changes of active ion transport systems of the CNS. The effect of superlethal doses of ionizing radiation on the Na,K pump in surviving brain slices]. / Postradiatsionnye izmeneniia v sistemakh aktivnogo transporta ionov v TsNS. Vliianie sverkletal'nykh doz ioniziruiushchei radiatsii na Na,K-nasos v perezhivaiushchikh srezakh mozga.

Active potassium ion transport in surviving sections of rat brain was irreversibly inhibited 6 min, 1 h and 6 h following whole-body single X irradiation. At the same time, the accumulation of products of lipid peroxidation and phospholipase hydrolysis was followed up during the development of radiation pathology. The relationship was noted between the postirradiation changes in the physicochemical status of lipids of the membrane and the impairment of its transport function.