Voprosy meditsinskoi khimii最新文献

The role of glutamate receptors in the brain spiking activity was evaluated. The electroencephalographic (EEG) spiking activity was monitored and autoreactive antibodies (aAbs) to subunits of glutamate receptors were assessed in the blood serum of epileptic and ischemic stroke patients. We showed that the level of GluR autoantibodies in blood serum of patients correlates to the intensity of the brain paroxysmal activity. These data confirm our previous observations. The level of GluR1 aABs has been proposed as a specific biomarker typical for epilepsy. This approach could be recommended as an additional criterion for diagnostic of nervous diseases such as epilepsy and ischemic stroke.

The effect of 16-20% medicinal preparation "Equalen" on some parameters of lipid metabolism in female rabbits with cholelithiasis induced by 40% clamp of common bile duct was investigated. The total course of Equalen administration for 90-120 days included daily oral administration of Equalen for 7 days followed by 3-4 day interval. The optimal dose was 1.5 ml per day (the effective range of doses varied from 1.2 to 2.0 ml). Such treatment resulted in disappearance of large and medium sized cholesterol formations from gallbladder, normalization of lipid metabolism in organs of hepatoenteric system and lipid composition of bile.

The review highlights current aspects of a large group of diseases the main pathogenetic element of which is an inherited or acquired disturbance of gene expression of nuclear or mitochondrial genome encoding mitochondrial proteins. The recent data on mutant genetic loci specific to the most wide spread mitochondrial diseases are considered. The steps of pathogenesis, include the mutations of nuclear or mitochondrial genes, disturbances of mitochondrial protein synthesis, dissipation of proton membrane potential, opening of a permeability transition pore, releasing of procaspases, cytochrome c, and other proapoptotic molecules, and finally chromatin fragmentation and apoptotic cell death. We discuss the possible reasons of polysymptomatic character and different variants of mitochondrial disease manifestations on the basis of the phenomenon of mitochondrial DNA heteroplasmy and metabolic compensation of the genetic defects. Modern biochemical methods of a mitochondrial disease diagnostics: (PCR-amplification, polarographic research of mitochondrial respiration and oxidative phosphorylation, analysis and monitoring of metabolites in biological liquids) are characterized. The basic principles and perspectives of the treatment of mitochondrial diseases, (gene therapy, correction of metabolic disorders, application of antioxidants and neuropeptides) are described.

The content and state of collagen in skin, muscle and bone of 2500-year-old Altai mummies were studied. Collagen is the predominant protein in studied tissues of the mummies. High degree of the resistance of collagen to the effect of various proteases (collagenase, pronase, pepsin) and to alkline and acidic hydrolysis suggests on the considerable chemical modification of tissue collagen structures of the mummy. The possibility of increased collagen cross-linkages in tissues of the mummies during long-term storage and of nonenzymatic glycosylation of collagen leading to the formation an Amadori products and other modified structures are discussed.

Information on the complete genome sequences of a number of organisms available recently offers essentially new opportunities for the development of new, highly effective antimicrobial compounds. In particular, the search for new effective antituberculosis drugs remains an important problem, due to the recent increase of number of patients suffering with tuberculosis. In this respect considerable attention is paid to the cyp51-like gene Rv0764c encoding sterol-14 alpha-demethylase belonging to the cytochrome P450 superfamily, which has been discovered by computer analysis of the Mycobacterium tuberculosis genome sequence. We have screened 64 clinical isolates of M. tuberculosis for functionally relevant mutations in the coding sequence of the gene encoding Cyp 51-demethylase by single-strand conformation polymorphism analysis (SSCP) and sequencing of PCR-amplified gene fragments. Structural analysis of the gene in the isolates revealed no mutations leading to amino acid substitutions in the corresponding protein. 10 isolates had a silent nucleotide substitution 114 GCT-->GCC. Computer analysis of cyp51 sequence of the CDC1551 strain also revealed a similar nucleotide substitution, which has not been mentioned previously. The data obtained demonstrate that the sequence of the gene is highly conserved, supporting the advisability of M. tuberculosis Cyp51 protein to be considered as a molecular target for new antitubercular drugs. The SNP found in the gene coding sequence may be employed in the studies of M. tuberculosis population genetics.

In the present study the level of myeloperoxidase in the human placenta at premature was investigated. Mycloperoxidase content did not depend on its localization in placenta and decreased at premature labour. It is suggested that the decrease in the myeloperoxidase content in placenta results in the weakening of antimicrobial barrier in the system mother-placenta-fetus and plays an important role in pathogenesis of premature delivery at later term.

Serum ceruloplasmih (CP) and anti-CP antibody levels were studied by the oxidase method in 18 healthy women and in 86 women with gynecological tumors. The results demonstrate that: 1) Serum CP concentrations increased in endometrial and ovarian cancer, in benign ovarian tumors and to a lesser extent in mioma of uterus. 2) Serum CP antibodies were found out in both benign tumors and cancer cases. 3) There was positive linear correlation between serum levels of CP and anti-CP-antibodies in endometrial and ovarian cancers, and in benign ovarian tumors.

The phenomenon of fast death of mice after parenteral administration of mink serum was explained by high activity of mink complement in particular by unusually high activity of its alternative pathway of activation. The presence of antibodies to mouse erythrocytes in mink serum was necessary precondition for their lysis under action of mink complement by classical and alternative pathways. However, removal of these antibodies resulting in cancellation of hemolysis did not effect toxicity of mink serum for nice in vivo. Partial decomplementization of mink serum zymosan completely prevented death of animals.

Pyruvate dehydrogenase, threonine aldolase and phosphoethanolamine lyase can produce acetaldehyde during normal metabolism. We studied the effect of loading with the substrates of these enzymes (pyruvate, 500 mg/kg, i.p., threonine 500 mg/kg, i.p., and phosphoethanolamine, 230 mg/kg, i.p.) on the blood concentrations of endogenous acetaldehyde and ethanol and the activities of enzymes producing and oxidizing acetaldehyde in the liver of normal rats and rats with liver injury provoked by chronic carbon tetrachloride (CCl4) treatment (0.2 ml i.p. per rat, 2 times a week during 4 weeks). Blood was collected before the treatment and then 30 min and 1 h following the administration of the substrates to intact and CCl4-treated rats. Endogenous acetaldehyde and ethanol were determined by headspace GC. The CCl4 treatment resulted in decreased liver alcohol dehydrogenase and aldehyde dehydrogenase activities and a significant elevation of liver endogenous ehtanol and a clear tendency to enhance blood acetaldehyde levels. Pyruvate increased blood endogenous acetaldehyde in CCl4-treated animals and endogenous ethanol--in the control group of animals. Threonine elevated endogenous acetaldehyde in normal rats. Phosphoethanolamine increased endogenous ethanol in the intact and CCl4 groups. At the same time, in CCl4-treated rats pyruvate administration increased the liver pyruvate dehydrogenase, threonine decreased threonine aldolase, whereas phosphoethanolamine decreased phosphoethanolamine lyase. Thus, the CCl4 effect on blood endogenous acetaldehyde and ethanol may be mediated through decreased liver ALDH and ADH activities. Liver injury promotes the accumulation of acetaldehyde, derived from physiological sources, including the degration of pyruvate and threonine by decreased acetaldehyde oxidation.