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Biomedical subjects

R I Volkova

Publications and source records attributed to R I Volkova.

At least 19 recordsLinked to original sources

[Mechanism of action of 2-aryloxy-2-thio-1,3,2-oxazaphosphorinane pesticides].

The interaction of 2-aryloxy-2-thio-1,3,2-oxazaphosphorinanes exhibiting nematocide, insecticide/acaricide, and synergetic activities with monoamine oxidases and the interaction of the corresponding oxones, 2-aryloxy-2-oxo-1,3,2-oxazaphosphorinanes, with various cholinesterases, carboxyl esterases, and monoamine oxidases were studied. We showed that the thioderivatives inhibited monoamine oxidases, whereas oxones, which are, as a rule, weak cholinesterase inhibitors, strongly inhibited carboxyl esterases of the American cockroach and were transformed with monoamine oxidases into the strong cholinesterase inhibitors, acyclic phosphamidates. This allowed us to explain the low toxicity of the thioderivatives, the high toxicity of the oxoderivatives, and the great difference in toxicities of thio- and oxocompounds in the 1,3,2-oxazaphosphorinane series. The capacity of thioderivatives to inhibit monoamine oxidases and of oxoderivatives and their further activation products to inhibit carboxyl esterases, i.e., both enzymes responsible for pyrethroid detoxication in insects, explains the synergetic activity of the 1,3,2-oxazaphosphorinane series.

Animals↗

Spatiotemporal dynamics of clotting and pattern formation in human blood.

We examined the spatial dynamics of in vitro clot growth in human blood and plasma and found that initially, a clot grows at a constant speed, then abruptly stops and becomes surrounded by an 'inhibition zone' in which coagulation is strongly suppressed. We also observed the formation of 'stratified structures' (target patterns) in which solid layers alternated with liquid plasma. These and other spatial regimes of clotting are explained in terms of two interacting concentration waves propagating without attenuation. The experimental results are consistent with a hypothesis that blood is a bi-excitable medium, a new type of excitable medium.

Blood Coagulation↗

Dynamics of clot growth induced by thrombin diffusing into nonstirred citrate human plasma.

The dynamics of clot formation was studied in a two-compartment chamber designed to allow free diffusion of thrombin according to its concentration gradient into nonstirred citrate plasma or fibrinogen solution. Fibrin clots in fibrinogen solutions increased progressively until the substrate was depleted. In plasma, the clot weight dynamics significantly depended on the concentration of thrombin in the thrombin compartment. When the thrombin concentrations were extremely low (25-40 nM), the clot weight increased throughout the experiment (sometimes 20-24 h). At higher thrombin concentrations, the clot weight increased for 1-2 h and then stopped growing for the following 3-4 h. The clot weight observed at the plateau varied only slightly in the range of thrombin concentrations of 50-770 nM. In this range, high thrombin concentrations (250-770 nM) caused a second increase in the clot weight 4-8 h after the start of diffusion, which was followed by the second plateau in the curve of clot weight against time. The time to the plateau and the plateau duration decreased with increasing thrombin concentrations. The abundant plasma inhibitors of thrombin cannot account for these results. It was hypothesized that an as yet unknown mechanism is responsible for the inhibition of clot growth.

Blood Coagulation↗

[Mechanism of action of thiophosphoroorganic insectoacaricides containing fragments of N-carbaalkoxylated amino acids].

Toxicity and insecticide and acaricide activity of compounds (1) is significantly dependent on the nature of amino acid (n = 1 or 2) and substituents in carbamate and amino acid ester groups (R and R1). Investigation of interaction of these compounds with mammalian carboxylesterases, and the appropriate "oxones" with choline esterases of mammal and arthropoda revealed that the lower toxicity and activity of beta-alanine derivatives (n = 2) compared with glycine derivatives (n = 1) are due to the more rapid hydrolysis by carboxylesterases (detoxication). The low toxicity of dithiophosphonate with R = Me, R1 = Bu(i), n = 1 and the high toxicity of its isomer with R = Bu(i), R1 = Me, n = 1 are associated with the more rapid oxidative cleavage of isobutyl group in comparison with the other substituents, because detoxication occurs by the cleavage of R1 and activation--by that of R respectively.

Acari↗

Calcium threshold in human plasma clotting kinetics.

In vitro clotting kinetics of citrate human blood plasma under its titration with calcium ions are studied. Contact activation (Factor XIa + plasma kallikrein) is shown to be independent of calcium while non-linear growth of thrombin concentration is demonstrated at calcium concentrations higher than 0.25 mM under conditions of contact activation caused by quartz walls of the measuring cell. Thrombin generation kinetics are well fitted with an exponential function. Power index of the exponential function steeply rises as calcium concentration increases from 0.25 to 0.5 mM and reaches plateau at higher concentrations. At free calcium concentrations under 0.25 mM thrombin level does not grow remaining lower than 30 pM. So, blood coagulation system behaves in a threshold manner under calcium concentration changes. The threshold concentration of free calcium is equal to 0.25 +/- 0.05 mM.

Amino Acid Sequence↗

[A filtration study of erythrocyte deformability].

The study of two flow methods (constant flow method and initial flow rate method) has been conducted to specify and compare methodological approaches to quantitation of red cell deformability. Washed red cells were resuspended in saline medium with glucose and albumin and examined for deformability by the above methods under different conditions. The parameters are presented to characterize flow curves obtained with the constant flow method. The authors have established optimal conditions for the measurements: the composition of the medium, the suspension HCT, leukocyte number, filtrate types, etc. With meeting of the above methodological requirements, both the methods permit quantitation of red cells deformability and can be utilized for stored blood and erythrocyte mass quality control.

Blood Flow Velocity↗

[Refractory effect and alloimmunization after transfusion of thrombocytes].

The authors discuss possible ways for prevention of alloimmunization with HLA-antigen in acute leukemia patients after platelet transfusions. Prevention or delay of HLA-alloimmunization is possible when platelets of single random donor are used instead of pooled random donor platelets for transfusions. The effect of leucocyte removal from platelet concentrates and ultraviolet irradiation of platelet concentrates under conditions of blood bank on alloimmunization and refractoriness incidence has been considered.

Anaphylaxis↗

[Isolation of thrombocyte concentrates from the leuko-thrombocytic buffy coats of donor blood and their preservation].

A new method has been developed for platelet concentrate (PC) preparation from the whole blood buffy coats. This method makes possible obtaining leukocyte-poor PC as compared to that prepared from platelet rich plasma. Functional characteristics of PC stored in Soviet plastic bags at room temperature (22 degrees C) under continuous agitation at circular rotator were studied during 7 days. Satisfactory maintenance of functional activity was noted during 5 days of PC storage. The method of PC preparation from the whole blood buffy coats can be also used for manual plateletpheresis of a single donor.

Blood Donors↗

[Development of the cerebellar glomeruli in the ontogeny of hens].

By means of light and electron microscopy development of the cerebellar glomeruli has been studied in the hen ontogenesis. Two successive stages have been revealed: protoglomerular (the 16th-18th days of incubation) and glomerular (the 19th day of incubation--the end of the 3d week after hatching). Specific peculiarities of their structural organization are presented. A suggestion is made on an inductive effect of the afferent mossy fibers on processes of morphological formation of the cerebellar glomeruli.

Animals↗

Combined action of nicotinamide and adenine in preservation of packed red cells.

An alkaline resuspension solution "Erythronaph" with adenine and nicotinamide has been developed. It allows to preserve red blood cells for 35 days. Removing leukocytes and platelets up to 90% by brief warning of 24-hour blood prior to centrifugation combined with return of 10% of plasma provide further prolongation of storage of red blood cells in "Erythronaph".

Adenine↗

[Development of dendritic spines in the piriform neurons of the cerebellar cortex in human prenatal ontogeny].

The submicroscopic investigation on developmental peculiarities of the dendritic spines in the piriform neurons of the cerebellar cortex has been performed during the human prenatal ontogenesis. The process of morphogenesis of the spines of the tertiary dendrites in the piriform neurons is demonstrated to start rather early--on the 24th week of embryogenesis and goes through three successive stages: 1) formation of a long cytoplasmic processes deprived of any membranous specialization; 2) formation of the terminal spinal head, making synapses with parallel fibers of the cerebellar cortex; 3) definitive stage. A suggestion is made that differentiation processes of the spines depend on inductive influence of the parallel fibers of the cerebellar cortex.

Cerebellar Cortex↗

Preparing platelet concentrates from banked blood stored for 1-5 days by using tetracycline antibiotics.

It was shown that storage of banked blood up to five days did not change number of platelets and their functional integrity was retained rather well. That made possible the development of a method for preparation of viable platelet concentrates (PC) from stored blood. This method is based on the reversibility of the tetracycline antibiotics inhibitory effect on platelet activation process. According to the results of our in vitro studies PC from stored blood seem to be suitable for clinical usage. This tetracycline method of PC preparation from stored blood may provide a more efficient utilization of available donor blood to meet the ever-expanding needs for PC transfusions.

Blood Platelets↗

[Multiple molecular forms of esterases from grass aphids inhibitory identification and stereospecificity].

Nine esterase fractions hydrolyzing 1-naphthylacetate were revealed in Triton X-100-solubilized extracts from aphides homogenates by polyacrylamide gel electrophoresis. The less mobile fractions 1-4 were identified as cholinesterases, using specific inhibitors--eserine and the cationic phosphoorganic inhibitor Gd-42; fractions 5-7 were related to carboxylesterases, using specific inhibition by triorthocresylphosphate and O,O-dimethyl (2,2-dichlorvinyl)phosphate. The most mobile fractions 8-9 which were resistant to the inhibitors, were classified as arylesterases. The aphis cholinesterase fractions revealed the highest mobility; the activity of carboxylesterase fractions was lower. Thiophosphonate--C8H17O(CH3)P(O)-SCH2SCH2COOCH3 was found to be a highly efficient selective inhibitor of aphis carboxylesterase, i. e. the kII values for carboxylesterase and cholinesterase were equal to 10(8) and 10(5) M-1 min-1, respectively. The thiophosphoorganic derivatives containing a beta-alanine residue in the cleaved part are more specific to acetylcholinesterase and carboxylesterase than those containing a valine residue. Studies with enanthiomers--C2H5O(CH3)P(O)SCH2CONHCH2CH2COOC2H5 and (C2H5O)2P(O)SCH2CONHCH(iC3H7)COOC2H5 have demonstrated that the asymmetry due to the central phosphorus atom is more essential for the acetylcholinesterase and carboxylesterase activities than that connected with the carbon atom in the cleaved part of the inhibitor molecule. During the interaction of the enanthiomers with the asymmetric phosphorus the stereospecificity of acetylcholinesterase is much higher than that of carboxylesterase. In terms of stereospecificity of the esterase site aphis acetylcholinesterase is is similar to its mammalian counterpart, while carboxylesterase from the same source is rather close to mammalian butyrylcholinesterase.

Animals↗

[Inhibition of cholinesterases by aziridinium derivatives of polymethylene bischloroethylamines].

Cyclization of polymethylene bischloroethylamines, differing in the methylene chain-length (n = 6 or 10) and the N-substituents (R = CH3 or CH2C6H5), was carried out and the respective aziridinium derivatives were obtained. These derivatives of hexamethonium and decamethonium manifested reversible inhibition (Ki approximately 100-1 microM) and irreversible alkylating activity (kII approximately 10(2) M-1 . min-1) towards acetylcholinesterase from human erythrocytes and horse serum butyrylcholinesterase. Upon varying n and R, the alkylation biomolecular rate constants changed symbately with changes in the reversible inhibition constants. The most potent alkylating agent with respect to acetylcholinesterase (kII 7,8 x 10(2) M-1 . min-1) and butyrylcholinesterase (kII 4,2 . 10(2) M-1 . min-1) was found to be the aziridinium analog of hexamethonium with R = CH2C6H5. Based on the kinetic data, the problem of alkylation of anionic sites in the catalytic and allosteric centers of the two cholinesterases is discussed.

Acetylcholinesterase↗

[Stereospecificity of active centers of acylcholinesterases].

The stereospecificity of the active center of acetylcholinesterase from human erythrocytes (AChE) and butyrylcholinesterase from horse blood serum (BuChE) in reactions with enantiomers of irreversible organophosphorus inhibitors (OPI) with asymmetrical central phosphorus atom and different structure of the leaving moiety: C2H5O(CH3)P(O)SR, where R = C2H7; C6H13: C4H4SC2H5; C2H4SC2H5 and C2H4S(CH3)C2H5, was studied. The strongest inhibiting effect with respect to cholinesterases was exerted by (-)-isomers of the OPI tested. The differences in the inhibiting activity of (-) and (+)-isomers were especially well-pronounced for OPI with R = C3H7 and C4H4SC2H5. The differences in the inhibiting activity of the enantiomers suggest that the stereospecificity of the active center of AChE was the highest and that of BuChE was considerably lower. After treatment by N,N-dimethyl-2-phenylaziridinium ions which specifically and irreversibly modify the anionic groups on the active surface of AChE, the stereospecificity of the latter is decreased and is approximated to that of BuChE. The differences in stereospecificity of AChE and BuChE are probably due to the considerable differences in the spatial structure of the enzyme active centers.

Acetylcholinesterase↗