[Quantum-chemical basics of pharmacokinetics (literary review and own investigations)].

The work is devoted to the use of quantum-pharmacological approaches in pharmacokinetic investigations. The main objective of the pharmacological researches is to find new, more active and less toxic drugs. To date, such a search is carried out empirically. The current approach can not fully meet the needs of medicine in the new drugs, requires considerable time and financial costs and does not meet modern standards of bioethics. Quantum pharmacology leads to the synthesis of drugs with desired properties is much faster and more efficient. Computer prediction of pharmacokinetic and biopharmaceutical properties of biologically active substances can make 50-70% more effective development of original drugs.

[Ishemic-reperfusion syndrome prophylaxis in general hypothermia in experiment].

The influence of general supercooling on rats were studied. The action of corvitin and pentoxiphillin on the prooxidant-antioxidant homeostasis for conditions of general supercooling were analysed. On the based of investigations results analysis of lipids peroxide oxidation indexes and antioxidant protection system in animals it were established, that corvitin in difference of pentoxiphillin give more significant protectory effect in conditions of ishemic-reperfusion syndrome.

[Pharmacological correction of energy metabolism disturbance in the inflammatory-dystrophic process in the periodontium].

The influence of lipoic acid on the energy homeostasis in rats with chronic generalized parodontitis has been investigated. Lipoic acid possesses the energy-saving activity, which is related to an increase in oxidative phosphorylation efficiency.

[Antihypoxants: their status and outlook]. / Antigipoksanty: sostoianie i perspektivy.

The survey deals with the up-to-date information in the literature on the problem of pharmacological correction of pathological changes found in the organism in the hypoxic syndrome. The principal approaches to pharmacotherapy of this pathological condition are pointed out. Information on the up-to-date and effective antihypoxia agents applied in medical practice and those in the stage of development is given.

[The role of cAMP phosphodiesterase inhibitors in the pharmacotherapy of the hypoxic syndrome]. / Rol' ingibitorov fosfodiésterazy tsAMF v farmakoterapii gipoksicheskogo sindroma.

The authors studied the pharmacotherapeutic activity of drugs belonging to various pharmacological groups which are inhibitors of cAMP phosphodiesterase in the hypoxic syndrome. The increase in the level of the secondary intermediate of the adenylate cyclase path in transmission of the intracellular signal from the outer surface of the cell to the nucleus, the hypoxia protector cAMP, under the effect of the drugs under study favorably influenced survival and the course of hypoxic hypoxia in overheating. A combination of quercetin bioflavonoid with acetylsalicylic acid demonstrated stronger antihypoxic and thermoprotector properties. The results were less marked with the use of the calcium channel blocker cinnarizine and an agent of the xanthine pentoxyfelline group. The possible mechanisms of the antihypoxic activity of the drugs under study are discussed.

[A biochemiluminescent analysis of the pharmacotherapeutic activity of acetylsalicylic acid in combination with quercetin in a hypoxic syndrome]. / Biokhemiliuminestsentnyi analiz farmakoterapevticheskoi aktivnosti atsetilsalitsilovoi kisloty v kombinatsii s kvertsetinom pri gipoksicheskom sindrome.

The effect of acetylsalicylic acid in combination with quercetin on blood serum biochemiluminescence in the hypoxic syndrome was studied. Possessing marked antioxidant activity, this drug combination prevented changes in the kinetics of blood serum luminescence in all periods of the investigation.

[The possible mechanisms of the antioxidant action of calcium channel blockers in the hypoxic syndrome]. / Vozmozhnye mekhanizmy antioksidantnogo deistviia blokatorov kal'tsievykh kanalov pri gipoksicheskom sindrome.

The influence of calcium channel blockers on pro-oxidant-antioxidant balance in hypoxic syndrome is studied. Both verapamil and cinnarizine were shown to prevent formation and accumulation of lipid peroxidation products in the tissues and normalize the basic components of the system of antioxidant protection. Probable mechanisms of the antioxidant action of the calcium channel blockers are discussed.

[Electron donor capacity of various amino acids]. / Elektronnodonornaia sposobnosot' nekotorykh aminokislot.

Constants of equilibria of reactions of 13 amino acids with I2 have been determined. It is shown that the values of constants are determined by the nature of side radicals. The highest values of donor-acceptor characteristics are noted in sulphur-containing amino acids, triptophan, low ones--in hydroxy-amino acids. It is shown on the example of flavonoid quertzetin that formation of donor-acceptor bonds is characteristic of aminoacids parallel to the acid-base interaction.

[A comparative evaluation of the efficacy of pharmacotherapeutic agents in hypoxia in the presence of hyperthermia]. / Sravnitel'naia otsenka éffektivnosti farmakoterapevticheskikh sredstv pri gipoksii na fone gipertermii.

In conditions of acute hypoxia in the presence of hyperthermia drugs were shown to exhibit various degrees of protective activity. Antihypoxic action coupled with thermoprotective activity is manifested by beneficial affect on the course of the pathological process. It is quercitrol that proved to be the most effective drug; it is capable of correcting simultaneously the disturbances emerging in different links of the pathological process: effect on the processes of lipid peroxidation and metabolism of arachidonic acid as well as on the activity of enzymes belonging to the monooxigenaze system in the experiment.

[The effect of quercetin on the metabolic processes in combined body exposure to hypoxia and hyperthermia]. / Vliianie kvertsetina na metabolicheskie protsessy pri sochetannom vozdeistvii na organizm gipoksii i gipertermii.

Quercetin given in a dose of 100 mg/kg 3 hours before acute systemic hypoxia (10 ob%) combined with hyperthermia (43 degrees C) has been demonstrated to prevent a drastic activation of lipid peroxidation and arachidonic acid metabolism parallel to a marked decrease the activity of the body's antioxidative and detoxifying systems under the conditions studied. The pronounced pharmacotherapeutical effects was due to its antioxidative and antilipooxygenase activities and its ability to induce the hepatic monooxygenase system.

[Morpho-functional state of biomembranes after treatment with alkyl derivatives of 2,4-dinitrophenol]. / Morfofunktsional'noe sostoianie biomembran pri vozdeistvii alkilproizvodnykh 2,4-dinitrofenola.

The morphofunctional state of the rat liver biomembranes is studied under conditions of the peroral effect of alkyl dinitrophenols: dinitroorthocresole and secondary 2,4-dinitro-6-butylphenol. It is established that free radicals and products of peroxide lipid oxidation (diene conjugates, hydroperoxides, final products reacting with 2-thiobarbituric acid) are very important for realization of the membrane-tropic action of the above compounds. Possible mechanisms of development of the membrane-damaging action of these xenobiotics and their effect on the state of the mitochondrial respiratory chain are discussed. The membrane-tropic effect of alkyl dinitrophenols is confirmed by the results of electron-microscopic studies.

[Effect of phenobarbital on the kinetics of the change in the level of paramagnetic metalloprotein complexes in dinitrophenol poisoning]. / Vliianie fenobarbitala na kinetiku izmeneniia urovnia paramagnitnykh kompleksov nekotorykh metalloproteidov pri intoksikatsii dinitrofenolami.

EPR spectroscopy was used to study phenobarbital influence on the kinetics of paramagnetic complexes variability of metal proteins--cytochrome P-450 and iron-sulfur proteins of rat liver in acute oral poisoning with the dinitrophenol pesticides DNOK and dinoseb. It was proved experimentally that the barbiturate favoured marked prevention of the decrease of the content of cytochrome P-450 and iron-sulfur proteins, thereby protecting the detoxifying and energy liver system from dinitrophenol-induced injuries. It is discussed that phenobarbital may act both as an inducer of cytochrome P-450 and iron-sulfur proteins involved in electron transport of the mitochondria.

[Penetration and binding strength of cadmium and its complexes with dithiols in cells]. / Proniknovenie i prochnost' sviazyvaniia kadmiia i ego kompleksov s ditiolami v kletkakh.

It was shown in experiments with three types of cells (dog red cells, hepatic cells of newborn Wistar rats, and culture of the renal epithelium of Vero monkeys) that cadmium in complexes with dimercaptoethanol penetrates the cells in an 8-33-fold greater amounts than free cations of metal. Unithiol increases cadmium penetration in the cells by 1.6-3 times only. The strength of cadmium binding with dimercaptopropranolol in the cells is greater than that with unithiol and free cations. Albumin limits penetration of free cations of cadmium and of complexes with dimercaptothiol to a greater degree than that of cadmium complexes with unithiols. The reasons for the differences revealed are discussed.

[Kinetics of the change in the level of metalloproteins and free radicals in the liver of rats with acute poisoning by alkyl derivatives of 2, 4-dinitrophenol]. / Kinetika izmeneniia urovnia metalloproteidov i svobodnykh radikalov v pecheni krys pri ostroi intoksikatsii alkilproizvodnymi 2,4-dinitrofenola.

Electron paramagnetic resonance was used to study over time metal proteins (cytochrome P-450, cytochrome-c-oxidase, iron and sulfur proteins) and free radicals in rat liver under acute (LD50) oral intoxication with 2,4-dinitro-6-butylphenol and 2,4-dinitro-6-methylphenol used as pesticides. The authors describe the kinetics of variations in the content of metal proteins and free radicals under the effect of the above-indicated toxic agents. It is assumed that the triggering mechanism of the toxic action of dinitrophenols lies in the inhibition of the function of iron and sulfur proteins. Possible mechanisms of the disturbance of the energy and detoxifying systems of the body under experimental conditions described are reviewed.

[Molecular mechanisms of interaction between blood serum albumin and dinitroorthocresol]. / Molekuliarnye mekhanizmy vzaimodeistviia syvorotochnogo al'bumina s dinitroortokrezolom.

Interactions of dinitroortocresol with human blood serum albumin were studied using equilibrium dialysis, spectrofluorimetry and polarography. Two classes of binding sites were found in the protein molecule: high-affinity site, binding 4 molecules of cresol and a low-affinity site, binding up to 12 molecules. Binding of dinitroortocresol occurred simultaneously with alteration in the albumin molecule conformation.