Voprosy meditsinskoi khimii最新文献

Polymer dressings with encapsulated thrombin or synthetic peptides which can mimic thrombin action are employed for wound healing. Paper describes the method for preparation of these hydrogel composites of PVCL-CaAlg [poly(N-vinyl caprolactam-calcium alginate). The effect of encapsulated thrombin/peptides on tissue repair process have beet investigatat in vivo experiments using a mouse model of wound healing. The developed dressings accelerated wound healing: thascan be used as a basis for creation of novel formulations with controlled drug release for wound therapy.

It is established that ATP-dependent protease Lon family belongs to the serine-lysine peptide hydrolases clan. Significant similarity of amino acid sequences of proteases Lon and repressors LexA in the regions including the catalytic serine and lysine residues is revealed by comparing primary structures of different families of the enzymes with Ser-Lys catalytic dyad. The both Lon and LexA families are shown to be divided into two subfamilies in accordance with the nature of amino acids in the catalytically active serine environment. Putative DNA binding sites are revealed in proteolytic domains of Lon A subfamily. Similarities and distinctions of the all families peptide hydrolases of the clan in the regions of their active centers are discussed.

Development suitable for clinical researches of hemolytic methods of determination of functional activity of the first components of a complement has allowed to show diagnostic value of testing activity of complement components in comparison with their contents as antigens. It has predetermined necessity for building modern ELISA tests-systems for quantitative determination of functional activity of complement components. Such methods built for the first time allow to determine activity of components C1q, C2, C3, C4 (and a ratio of isotypes C4A and C4B), C1-inhibitor, factors B and D. Addition of these tests-systems ELISA systems for quantitative determination of components, and in case of C1-inhibitor of presence IgG, IgA and IgM autoantibodies against C1-inhibitor frames opportunities of an evaluation complement status of the patient, hereditary predisposition to such diseases as a stomach ulcer, the glaucoma, a clamidiosis, bacteroidosis, allows to carry out differential diagnostics of angioedema. Inhibition of covalent linkage C4b or C3b various endogenic and exogenous effectors during formation C3- and C5-convertases allows to understand processes of a regulation of a homeostasis, and also the mechanism of action of drugs.

Sensitivity of 293 human epithelial kidney cells transfected by human cytochrome CYP450 gene to cyclophosphamide was investigated. Transfection was carried out by plasmid DNA containing CYP2B6 gene complexed with cationic liposomes. Liposomes were prepared from mixture of cationic lipids and cholesterol at different molar ratios. Experimental protocol included the following steps: transfection of epithelial kidney cells by complexes of plasmid DNA-cationic liposomes, clone selection in the medium with antibiotic Geneticin G418, selected clone harvesting and their treatment by cyclophosphamide as following cytotoxicity evaluation. It was shown that addition of 0.25 mM of cyclophosphamide resulted in death of 40-45% transfected cell population.

Cytochromes P450 (CYPs) play an important role in the oxidative metabolism of xenobiotics. Three-dimensional structures of CYPs are needed to study structure-function relationships in their molecules and interaction with partner proteins. Experimental determination of eucaryotic CYPs 3D structures is difficult because of hydrophobic membrane anchors and surface hydrophobic regions that prevent their crystallization. Replacement of surface hydrophobic amino acids by hydrophilic residues without any changes in protein structure and function can help to solve this problem. Such modification can be proposed using the analysis of 3D model of protein. In this work computer aided 3D structure of microsomal P450 2B4 (CYP2B4) was modeled for the further prediction of surface mutations for hydrophilization of the protein surface. The model of 3D structure of CYP2B4 was constructed by homology with CYP2C5 Model optimization was made by energy minimization and molecular dynamics simulation of protein molecule in water environment. The model was verified by using special statistic software and by comparison with the experimental data on the substrate recognition site, redox-partner binding sites and chemical modification of the protein surface.

The influence of gamma-GluHA and glutarylhistamine on the lipid peroxidation, cholesterol, phospholipid and liver aminotransferase activity was investigated using carbon tetrachloride-induced model of subacute liver damage. Pretreatment of rats with gamma-GluHA and glutarylhistamine prevented liver necrosis and normalized activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in blood plasma, lipid peroxidation in the liver and plasma, lipid profiles and cholesterol content in the liver and plasma.

Function of rat liver cytosolic glucocorticoid receptors in the haemorrhagic shock and the effects of verapamil and nifedipine were investigated. Nifedipine administration normalised hepatic receptor functioning affected by the shock. Verapamil administration to animals subjected to shock treatment caused further suppression of the receptor functioning. Both drugs reduced blood corticosterone level in hemorrhagic animals up to control level. Verapramil potentiated hypotension and this deteriorated the course of posthamorrhagic period. This effect may be at least partially attributed to verapramil-induced inhibition of glucocorticoid receptor type II. Nifedipine maintained BP in the subnormal level and reduced the number of animals with the decompensated shock course, which is probably associated with its positive influence on glucocorticoid receptor properties and permits to recommend an introduction of this drug into the complex therapy of the shock.

Endogenous free radicals, in particular, reactive species of oxygen, nitrogen, chlorine cause DNA oxidation which is potentiated by exogenous prooxidant factors. The free radicals cause various DNA damages. This review highlights one of them, oxidative modification of guanosine, and also modern methods of the estimation of oxidized guanosine (8-oxodG) content. The numerous data on an induction of 8-oxodG in DNA by exogenous genotoxicants in vitro and in vivo are presented. 8-oxodG is used as a biomarker of DNA oxidation, accompanying some human diseases.

Long-term limitation of motor activity of male rats is accompanied by impairments of mitochondrial ADP phosphorylation in liver and heart. The most significant changes were observed after 15 and 45 days of hypokinesia. Administration of GABA and pyracetam to animals subjected to hypokinesia induced a tendency to "normalization" of ADP phosphorilation processes.

The activities of key enzymes of pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G-6 PD) and 6-phosphogluconate dehydrogenase (6-PGD), were studied in cytoplasmatic fractions of brain cortical (limbic, orbital, sensorimotor cortex) and subcortical (myelencefalon, mesencefalon, hypothalamus) structures of rats subjected to starvation for 1, 2, 3, 5 and 7 days. Short-term starvation (1-3 days) caused activation of 6-GPD and 6-PGD both in cortical and subcortical structures. Long-term starvation for 5-7 days caused a decrease of activities of the pentose phosphate pathway enzymes in all studied structures. It is suggested that enzymes of pentose phosphate pathway in nervous tissues are functionally and metabolically related to glutathione system and during starvation they indirectly participate in the regulation lipid peroxidation processes.