PubMed Health⌕ Search

Biomedical subjects

I N Topchieva

Publications and source records attributed to I N Topchieva.

36 records · Page 2Linked to original sources
PubMed1991

Block copolymers of ethylene oxide and propylene oxide (pluronics) as immunomodulators and antitumour agents.

Block copolymers of ethylene oxide and propylene oxide (pluronics) are nontoxic water-soluble membranotropic surfactants available as polymers with various compositions, molecular masses, number, and arrangement of blocks. In vivo experiments are reported which demonstrate that these polymers and their functional derivatives stimulate the production of anti-sheep-erythrocyte antibodies in mice. The introduction of reactive (hydroperoxide) groups into the polymers by chemical modification or by solubilization of low-molecular-mass hydroperoxides alters the properties of these immunostimulators. In vitro experiments revealed that these modified polymers enhance the activity of natural killer cells without reducing their viability. It is proposed that the immunomodulatory properties of pluronics and their derivatives play an important role in the antitumour activity of these substances in vivo.

Animals↗
PubMed1991

The interaction of block copolymers of ethylene oxide and propylene oxide and their polymer-protein conjugates with lipids.

The interaction of block copolymers of ethylene oxide and propylene oxide with lipid structures-monolamellar and multilamellar vesicles from egg yolk lecithin and dipalmitoylphosphatidylcholine-was studied by differential scanning calorimetry, light scattering, and electron spin resonance. Copolymers with different ratios of hydrophilic: hydrophobic portions, numbers of polymers, and arrangements or positions of the blocks, as well as conjugates of polymers with proteins, were used. Peculiarities in the macromolecular structure of the copolymers influence the character of their interactions with lipids. The effects of copolymers which become incorporated into the lipid bilayer are compared with that of polyethyleneglycol which influences lipid structure in an indirect manner.

Electron Spin Resonance Spectroscopy↗
PubMed1991

[Problems of biomimetic chemistry].

The main goals of biomimetic chemistry have been formulated on the basis of the concept of biochemical organization. Biomimetic chemistry is defined as a science which employs the principles of biochemical organization (i. e., the principles of structural organization, functioning and regulation of biological systems at the levels corresponding to biomacromolecules, supramolecular complexes and subcellular structures) for the construction of artificial systems with predetermined properties or for conferring desired properties on natural biochemical systems with the help of artificial elements. The relationships between biomimetics and biochemical modelling are discussed. As examples of biomimetic systems, some enzymes entrapped into hydrated reverse micelles of a surfactant in an organic solvent and conjugates of proteins with polyalkylene oxidases are considered.

Biochemical Phenomena↗
PubMed1987

[Polyethylene oxide-based artificial antigens. An experimental study of the kinetics of the distribution of polyethylene oxide derivatives].

125I-labeled derivatives of iodaryl-polyethylene oxide with mol. wt. equal to 3 X 10(3), containing and not containing dinitrophenyl (DNP) residues (haptens), were obtained. The capacity for anti-DNP response was shown to be unaffected by the presence of the iodaryl group. The pharmacokinetics of both derivatives of polyethylene oxide were studied in experiments on noninbred white rats receiving these derivatives intravenously in doses of 0.53-0.80 mg/kg. These experiments revealed the following differences in the pharmacokinetics of the derivatives under study: the presence of the DNP group led to an increase in the level of polymer fixation in the body of the animals, particularly in their blood, liver and spleen. Differences in the content of radioactive substances in other organs were not statistically significant.

Animals↗
PubMed1984

[Antigenic properties of nitro aromatic derivatives of polyethylene glycol].

The immunogenic properties of the dihapten and monohapten derivatives of polyethylene glycol with different nitroaromatic groupings were studied. 2,4-dinitrophenyl, 2, 4, 6-trinitrophenyl and trinitrophenyl-ethyl groupings were used as hapten groups. The injection of monohapten compounds was found to induce the accumulation of antibody-forming cells secreting antibodies to trinitrophenyl in the spleen of normal and athymic nude mice. As early as on day 3 the number of antibody-forming cells considerably exceeded their background level, the process of B-cell activation being, to a certain extent, thymus-independent. Dihapten compounds were not immunologically active. The effect rendered by the nitroaromatic derivatives of polyethylene glycol, revealed in this study, is linked with the known capacity of polyethylene glycol to adsorb on the surface of cell membranes.

Animals↗
PubMed1981

[Polymerization of bacterial flagellar flagellin in the presence of polyethyleneglycol].

Polymerization of flagellin from the flagella of Bacillus brevis in the presence of polyethyleneglycol (PEG) with molecular weight varying from 400 to 40 000 was studied. When 10% PEG2000-6000 was used, polymerization was completed within 5 min. When PEG with higher molecular weights were used, their higher concentrations were necessary. Polymerization of flagellin in the presence of PEG400-600 did not practically differ from that without PEG. At flagellin concentrations up to 0.1 mg/ml the polymerization process with PEG also occurred at a very high rate. Polymerization of flagellin obtained by heating of bacterial flagella in the presence of PEG did not require exogenous primer. A possible mechanism of flagellin polymerization in the presence of PEG is discussed.

Bacillus↗
PubMed1979

[Effect of polyethylene glycol on association of muscle phosphorylase B].

It has been shown that a neutral polymer poly(ethyleneglycol) with molecular weight of 4000 and more shifts the equilibrium between the dimer and tetramer forms of phosphorylase B from rabbit skeletal muscles in the direction of formation of species with higher molecular weights. Poly(ethyleneglycol) with molecular weight below 600 has no effect on the association process. Phosphorylase B is precipitated in the form of crystals in the presence of poly(ethyleneglycol) mol. weight 40,000), when the concentration of the latter is higher than 50 mg/ml. AMP and sulfate ions are required for the crystallization process.

Chemical Phenomena↗
PubMedDate not supplied

Synthesis and physicochemical properties of protein conjugates with water-soluble poly(alkylene oxides).

Conjugates of proteins (bovine serum albumin (BSA) and alpha-chymotrypsin (CHT) with poly(ethylene glycol) and amphiphilic block copolymers of ethylene oxide and propylene oxide (proxanols) were synthesized, using monoaldehyde polymer derivatives as the amino group modifying reagents. Four types of conjugates varying in the placement of hydrophobic block and type of polymer chain distribution were obtained. Methods of purification and characterization of proteins conjugated with proxanols were developed. It was shown that conjugates based on CHT retain high enzymatic activity toward both substrates investigated--N-benzoyl-L-tyrosine and casein-up to high degrees of modification (11 polymer chains per protein molecule). At the same time, CHT--proxanol conjugates were characterized by higher thermostability, the stabilizing effect increasing in parallel with the degree of modification. It was shown that the alteration of sedimentation coefficients of proteins caused by modification was negligible. On the basis of data obtained by the methods of hydrophobic chromatography, sedimentation, and differential scanning calorimetry, conformational models of protein-proxanol conjugates were suggested. It was supposed that conjugates form compact structures in aqueous solutions, which resemble intramolecular micelles, stabilized by hydrophobic interactions between poly(propylene oxide) blocks of proxanols.

Chymotrypsin↗
PubMedDate not supplied

Protein conjugates with water-soluble poly(alkylene oxide)s entrapped in hydrated reversed micelles.

Conjugates of alpha-chymotrypsin (ChT) with poly(ethylene glycol) (PEG) and block copolymers of ethylene and propylene oxides (proxanols) have been synthesized. The molecular mass of the polymers used was 2 kDa. The conjugates contained five to seven polymer chains per enzyme molecule. Hydrolysis of N-trans-cinnamoylimidazole catalyzed by the conjugates of ChT with poly(alkylene oxide)s was studied in 0.05 M Tris-HCl buffer at pH 8.0 and in the system of the hydrated reversed micelles of aerosol OT (AOT) in octane at 25 degrees C. The deacylation rate constant k3 for the conjugates in buffer solution was 1.5-1.8-fold higher than that for native ChT. The value of the [H2O]:[AOT] ratio corresponding to the maximum on k3 versus [H2O]:[AOT] curves for the conjugates (ca. 16) allows the dimensions of their molecules to be evaluated. The radius of the conjugate molecules was found to be about 2.8 nm. The value of k3 for the conjugate of ChT with PEG, as in the case of native ChT, remains constant when the concentration of AOT is varied. However, the deacylation rate constant for the conjugates of ChT with proxanols decreases with the increase in AOT concentration, which indicates that these conjugates are able to interact with the micellar matrix and therefore may be considered membranotropic compounds.

Buffers↗
PubMedDate not supplied

Novel derivatives of cyclodextrins, modified with poly(ethylene oxide) and their complexation properties.

A new family of bouquet-like molecules based on cyclodextrins is described. These compounds were obtained by polymerization of ethylene oxide. This reaction was initiated by primary and secondary hydroxyl groups of cyclodextrins, which constitute an organizing core. Analysis of structure and composition of conjugates based on alpha-CD and beta-CD was performed using the data of MALDI-MS, GC-MS, and 13C-NMR spectra. Glass transition behavior of the conjugates shows that the above compounds are amorphous. Complexation properties of the conjugates are described with respect to sodium 4-nitrophenolate and calcium acetylhomotaurinate, which are used as guest molecules. Binding interaction between cyclodextrins or their conjugates and sodium 4-nitrophenolate was studied using differential absorption spectra. Association constants Ka between CD hosts and calcium acetylhomotaurinate composed of two equal anionic moieties were studied using 1H-NMR spectroscopy. The values of binding constant for beta-CD were found to increase by more than 2 orders of magnitude than that of the corresponding system based on alpha-CD. alpha-CD was shown to form the inclusion complex with one anionic moiety, whereas beta-CD produces a ternary complex with two anionic moieties of CAHT. For PEO derivatives of CDs, Ka decreases as compared with that of parent CD for both guests. These conjugates may be used as potent drug-delivery systems.

Acamprosate↗
PubMedDate not supplied

Noncovalent adducts of poly(ethylene glycols) with proteins.

A new method of preparation of noncovalent complexes between poly(ethylene glycol) (PEG) and proteins (alpha-chymotrypsin (ChT), lysozyme, bovine serum albumine) under high pressure has been developed. The involvement of polymer in the complexes was proved using (3)H-labeled PEG. The composition of the complexes (the number of polymer chains per one ChT molecule) depends on the molecular mass of PEG and decreases with the increase in molecular mass from 300 to 4000, whereas the portion of the protein (wt %) in complexes does not depend on the molecular mass of incorporated PEG and corresponds to approximately 70 wt %. The kinetic constants for enzymatic hydrolysis of N-benzoyl-L-tyrosine ethyl ester and azocasein catalyzed by the PEG-ChT complexes are identical with the corresponding values for the native ChT. According to the data obtained by the method of circular dichroism, the enzyme in the complexes fully retains its secondary structure. The steric availability of PEG polymer chains in the complexes was evaluated by their complexation with alpha-cyclodextrin (CyD) or polymer derivatives of beta-CyD modified with PEG (PEG-beta-CyD). In contrast to free PEG, only part of PEG polymer chains ( approximately 10%) interact with alpha-CyD. Thus, the complexation of PEG with ChT proceeds by means of multipoint interaction with surface groups of the protein globule located far from the active site and results in the sufficient decrease in the availability of polymer chains. The complexes between PEG chains in PEG-protein adducts and PEG-beta-CyD may be considered as a novel type of dendritic structures.

Chymotrypsin↗
PubMedDate not supplied

[The immunomodulating properties and antitumor activity of block copolymers of ethylene oxide and propylene oxide (proxanols)].

Influence of block copolymers of ethylene and propylene oxides (proxanols) on the human natural killer activity was studied. Proxanols had no effect on the lymphocytes viability and increased their cytotoxic activity against target cells K 562 in vitro. Certain antitumor properties of proxanols were demonstrated in vivo (especially for ascitic tumors). The proxanols activity was chiefly determined by the membranotropic properties of its main polymer chain.

Adjuvants, Immunologic↗
PubMedDate not supplied

[A radioisotope method for assessing the anaphylactogenicity of polymer drugs].

A radioisotope technique has been developed for the quantitative assessment of microcirculation disorder in a local anaphylactic focus of guinea pigs sensitized with horse immunoglobulin G and polyethyleneoxide conjugate with 2,4-dinitrophenol. The technique is based on the use of a radioactive tracer, dextran derivative, labelled with radionuclide 125I. The method can be used for studying a safety of new polymer-containing drugs.

Anaphylaxis↗