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Using standard forms of immunoglobulin (Ig) G and albumin, we have studied electrophoretic and chromatographic profiles of samples of pharmaceutical blood biopreparation batches. The usability of standard proteins was also demonstrated by testing analytical characteristics of immunoperoxidase conjugates specific to human and animal IgG (anti-IgG IPC). In particular, we suggest an additional estimation of analytical characteristics of anti-IgG IPC by the enzyme reaction kinetics with the standard dilution which is calculated by the direct enzyme-liked immunoassay on the homologous IgG-antigen.

Results obtained from complex medical-physiological investigations performed during 10 scientific expeditions in the Arkhangel'sk Region in 2003-2005 are presented. The effects of climatological-geographic, biogeochemical, and social conditions of the conditions obtaining in the Far North region of Russia on sexual maturation, formation of the structural-functional organization of the brain, autonomic functions, and immunological and biochemical status of schoolchildren were studied using state-of-the-art neurophysiological methods (computerized electroencephalography, computerized rheoencephalography, computerized electric dipole origin tomography, etc.), psychophysiological and psychometric methods (assessment of the state of cognitive and memory functions, Wechsler intellectual scale), along with biochemical assay of monoamine oxidase (MAO, the key enzyme in adrenergic neurotransmitter metabolism) and the liver enzyme butyrylcholinesterase (BuChE) and physicochemical analysis of the levels of macroelements and trace elements in the body.

Results of complex medical-physiological research performed during 10 scientific expeditions in Arkhangelsk region in 2003-2005 are presented. Influence of climatic-geographic, biogeochemical and social conditions of North-West region of Russia on sexual maturation, formation of the brain structural-functional organization, vegetative functions, immunological and biochemical status of schoolchildren was studied with the aid of modern neurophysiologic (computer electroencephalography, computer rheoencephalography, computed electric dipole origin tomography, etc.), psychophysiological and psychometric methods (evaluation of cognitive and mnestic functions, Vechsler 1Q estimation), biochemical assessment of monoamine oxidase and butyrylcholinesterase activity, physical-chemical analysis of macro- and microelements in the organism.

The antienzymic activities of 14 organophosphorous compounds, the derivatives of dialkyl thiophosphoric acid, towards the acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and carboxylesterase (CE) from the spring grain aphid and mammals were investigated. The dependence of inhibitory activity of the compounds on their alkyl radical length was shown to be different for the AchE from the aphid and man. Some less pronounced differences in this dependence were revealed between the BuChEs from the aphid and horse as well as between the CEs from the aphid, mouse and red spider mite. The data give evidence of a distinction in structure of the active surfaces of the enzymes from the aphid and mammals. Some peculiar properties of the aphid cholinesterases are discussed taking account of the results of the present and previous papers.

It is the first time when the substrate specificity is considered as a complex phenomenon, taking into account an influence of substrate structure on the rate of enzymatic hydrolysis and interaction of cholinesterases with reversible and irreversible inhibitors. Kinetic parameters of hydrolysis of 18 esters, including choline, ammonium and indophenol derivates, are presented, as affected by cholinesterase from optical ganglia of pacific squid Todarodes pacificus, by acetylcholinesterase from human erythrocytes and by butyrylcholinesterase from horse serum. Some peculiarities of the squid cholinesterase are revealed, which are as follows: a low specificity at a rather high hydrolytic efficiency, the sensitivity towards inhibitory effects of several substrates at high concentrations. Reversible inhibition of the squid enzyme by ammonium inhibitors was dependent on the nature of substrates to a greater extent than that of the other enzymes. The substrate structure also conditioned various aspects of "the protective effect" in the course of irreversible inhibition of the squid cholinesterase by organophosphorous inhibitors.

The research of interaction of cholinesterases from human erythrocytes, horse blood serum, brain of the frog Rana temporaria, optical ganglia of the Pacific squid Todarodes pacificus, as well as optical ganglia of specimens of the Comandor squid Berryteuthis magister from different areas in the Bering sea with 13 organosilicon bis (trimethylammonium) compounds (silane and siloxane rows) as reversible cholinesterase inhibitors have been first studied and generalized. Calculations of the effector structure using the method of theoretical conformational analysis showed higher rigidity of interonium chain of siloxane derivatives and gave grounds to accept the asymmetry of hydrate envelope for these compounds. The data of conformational and kinetic analysis allowed to propose that specificity of antienzymic effect of organosilicon compounds was mainly due to conformational flexibility of interonium chain and the nature of hydration of effector molecule. The new information on the mechanism of catalytic reactions effected by cholinesterases from animals at different evolutionary stages was obtained.

Conformational and geometrical properties of the hexamethylenebis(trimethylammonium) (CH3)3N+-(CH2)6)-N+(CH3)3 (hexamethonium) and its derivatives with various degree of conformational flexibility of interonion chain having disulfide or two dimethylsilane groups or difluoromethylene chain instead of cholinesterase reversible inhibitors have been determined using molecular mechanics methods. Conformation-activity relationships between these inhibitors and different cholinesterases (human erythrocyte acetylcholinesterase, horse plasma butyrylcholinesterase, cholinesterase from the brain of the grass frog Rana temporaria and optical ganglia from the Pacific squid Todarodes pacificus and Comandor squids Berryteuthis magister from various areas) were investigated. Hypothesis of complex influence of conformational and geometrical properties (if molecules on anticholinesterase efficiency of compounds under investigation was formulated.

Conformational properties of a series of polymethylenebis (trimethylammonium) derivatives [formula: see text] (n = 4-10), cholinesterase reversible inhibitors, were studied by molecular mechanics method. Conformation-activity relationships between these inhibitors and human erythrocyte acetylcholinesterase, horse plasma butyrylcholinesterase, cholinesterases from the brain of the frog Rana temporaria and from visual ganglia of the squid Todarodes pacificus were investigated by correlational methods. Differences in mechanisms of antienzyme actions were determined.

Kinetic parameters of 9 substrates interaction with glutathione transferase (GST) from spring grain aphid and rat were studied. The most significant difference in Vmax values was noticed for 4-nitropyridine-N-oxide (6 times higher for aphid) and ethacrynic acid (7 times higher for rat). Km values were practically in all cases higher for aphid GST as compared to rat GST. New class of effectors of GST suggested by us, that is azimines (2 series), was used for the inhibitor analysis. GST interaction with these inhibitors was appreciated by three types of activity: nucleophilic replacement, thiolysis and N-deoxygenation. It has been shown that the degree of GST inhibition depended considerably both on the GST source and the substrate used. New high-effective inhibitors of GST were found among azimines and their higher specificity to rat GST as compared to aphid GST was demonstrated especially in thiolysis reaction.

Three reactions (nucleophile substitution, thiolysis and N-deoxygenation) catalyzed by rat liver glutathione transferase have been studied using several N-heterylazimine inhibitors. The inhibitors are sharply different in their effectiveness in the transferase reactions. Their efficiency depends on their structure. The mechanism which underlies the found regularities is suggested.

The interaction of rat liver glutathione and glutathione transferase with several 1-phthalimidoazimines is studied. Differences between spontaneous and enzymatic reactions of azimines and reduced glutathione are shown. It is pointed out that the formation of glutathione-azimine complexes takes place in the reaction mixture.

Studies have been made of the effect of several organophosphorus inhibitors, R1(R2)P(O) . SCH2CH2SR and R1(R2)P(O)SCH2CH2SRR . -O4SCH3 (or -I), which differ by the structure of split (R, P) and phosphoryl (R1, R2) parts of the molecule, on cholinesterase (ChE) from the brain of the fly Delia brassicae, acetylcholinesterase (AChE) of the bovine erythrocytes and butyrylcholinesterase (BuChE) from the blood serum of the horse. For fly ChE, higher values of a constant (kII) of the inhibition rate (at pH 7.5 and temperature 25 degrees C) were obtained both with thiophosphates and with thiophosphonates. This finding reveals higher reactivity of the active centre of this enzyme, as well as significantly lower selectivity of the latter to the structure of organophosphorus inhibitors. The data obtained suggest the existence of differences in the size of hydrophobic regions of anionic and esterase parts of the active centre in ChE of the fly and AChE of mammals, as well as the existence of some similarity between ChE of the fly and BuChE.

The assimilation of purine and pyrimidine bases, their nucleosides and orotic acid from the host cell by coccidian E. tenella was studied by means of radioactive precursors of DNA and RNA. It has been established that within their development and reproduction the parasites use selectively different precursors of DNA and RNA from the host cell. Coccidians use intensively the purine base 14C-adenine, assimilate negligibly the pyrimidine base 14C-uracil and nucleoside 14C-uridine and do not use at all 14C-thymidine and 14C-thymine. The coccidians were found to assimilate most intensively 14C-orotic acid, the lower precursor of pyrimidine bases.

The infection of chicks with optimal immunogenic doses of oocysts of E. tenella and E. acervulina results in the activation of biosynthesis of proteins and nucleic acids in the Fabricius bursa, spleen, thymus and blind processes of the intestine. The infection causes the increase in the quantity and synthesis intensity of immunoglobulins G and M that suggests a stimulation of cellular and immunity factors in the ogranism of an immunized bird. Maximum changes in biosynthesis of compounds studied are reported four days after the infection that confirms high immunogenic properties of the second generation schizonts. A study of protein synthesis in limphoid organs of chicks infected only with E. tenella has yielded the same results. The infection with E. acervulina caused but negligible changes in the protein metabolism, i.e. coccidians of E. tenella possess more immunogenic properties.

The RNA fraction and the intensity of their turnover in chick liver during experimental coccidiosis was studied. A marked (about 60%) increase of intensity of mRNA turnover with no changes in its amount was found. It was shown that pre-rRNA biosynthesis was significantly enhanced and, due to it, the amount of both pre-rRNA and mature 18S rRNA was increased while the level of 28S rRNA was unchanged. The relations between the observed changes of RNA biosynthesis and protein biosynthesis in liver in coccidiosis as well as the role of these changes in pathological process studied are discussed.