Effect of the phase state of lipids on their interaction with cobra cytotoxin

Interaction between cytotoxin of the Central Asia cobra venom and dimiristoylphosphatidylcholine bilayer depending on its phase state was studied by ESR with spin label. A conclusion can be drawn that the efficiency of cytotoxin effect on the membranes depends on their phase state. Cytotoxin molecules are incorporated into myophile region of the bilayer, only if the latter is in the liquid crystal state. The interaction between cytotoxins and lipids of the bilayer in a gel state is in the main conditioned by electrostatic forces.     

Antitumor activity of amides of dihydrobetulonic acid in vitro and in vivo

Amides containing homopiperidine and piperazine cycles were synthesized from dihydrobetulonic acid obtained by the oxidation of dihydrobetulin. All substances were shown to have a high antitumor activity (CCID₅₀ = 3.5–36.2 μM) in vitro in lymphoid (CEM-13, U-937) and monocytic (MT-4) human cell lines. Amides containing the methyl- and ethylpiperazine residues do not influence the viability of Lung Lewis Carcinoma cells in culture and do not have a significant effect on its transplants in C57BL/6 mice. However, these amides efficiently inhibit the development of metastases in lungs of these mice. The antimetastatic activity of the studied amides increases with changing the methyl by ethyl aliphatic residue in the piperazine cycle.     

Characteristics of X-ray Emission from a Micropinch Discharge at Different Polarities of the Discharge Electrodes

Plasma Physics Reports - The measurement technique and results are presented from studies of the X-ray spectra and X-ray yield from micropinch discharge plasma in a low-inductive vacuum spark...     

Quantitative trait locus analysis of fungal disease resistance factors on a molecular map of grapevine

A full-sibling F1 population comprising 153 individuals from the cross of Regent × Lemberger was employed to construct a genetic map based on 429 molecular markers. The newly-bred red grapevine variety Regent has multiple field-resistance to fungal diseases inherited as polygenic traits, while Lemberger is a traditional fungus-susceptible cultivar. The progeny segregate quantitatively for resistances to Plasmopara viticola and Uncinula necator, fungal pathogens that threaten viticulture in temperate areas. A double pseudo-testcross strategy was employed to construct the two parental maps under high statistical stringency for linkage to obtain a robust marker frame for subsequent quantitative trait locus (QTL) analysis. In total, 185 amplified fragment length polymorphism, 137 random amplified polymorphic DNA, 85 single sequence repeat and 22 sequence characterized amplified region or cleaved amplified polymorphic sequence markers were mapped. The maps were aligned by co-dominant or doubly heterozygous dominant anchor markers. Twelve pairs of homologous linkage groups could be integrated into consensus linkage groups. Resistance phenotypes and segregating characteristics were scored as quantitative traits in three or four growing seasons. Interval mapping reproducibly localized genetic factors that correlated with fungal disease resistances to specific regions on three linkage groups of the maternal Regent map. A QTL for resistance to Uncinula necator was identified on linkage group 16, and QTLs for endurance to Plasmopara viticola on linkage groups 9 and 10 of Regent. Additional QTLs for the onset of berry ripening (veraison), berry size and axillary shoot growth were identified. Berry color segregated as a simple trait in this cross of two red varieties and was mapped as a morphological marker. Six markers derived from functional genes could be localized. This dissection of polygenic fungus disease resistance in grapevine allows the development of marker-assisted selection for breeding, the characterization of genetic resources and the isolation of the corresponding genes.Communicated by H.C. Becker     

Investigations of high-energy electrons of the microwave discharge plasma at configuration of the “Magnetor” Bi-dipole magnetic confinement system by X-ray radiation analyses

The results of the investigations of a group of fast electrons in a microwave discharge plasma in the “Magnetor” magnetic trap are presented. The data on the presence and location of this group of electrons is important for estimating the total plasma pressure taking the previous probe measurements into account. Fast electrons are found to be localized within the magnetic separatrix in the region of confinement of the main plasma. The maximal energy of fast electrons is higher than 25 keV.     

The influence of cytotoxins from Central Asian cobra venom and melittin from bee venom on the thermodynamic properties of phospholipid bilayer

The interaction of cytotoxin Vc1 and Vc5 from Central Asian cobra and melittin from the bee venom with multilayer liposomes prepared from dimiristoylphosphatidylcholine with an addition of phosphatidic acid have been studied by the method of differential scanning calorimetry. Incorporation of Vc1, Vc5 and melittin into the lipid resulted in pronounced changes in the thermodynamic properties of the lipid. Polypeptides studied induced lateral phase separation in the lipid. Interaction between molecules of the toxins and the lipid resulted in the formation of a new lipid phase characterized by a higher melting temperature and lower phase transition enthalpy.     

Polymethyleneamine Alkaloids of Animal Origin: I. Metabolites of Marine and Microbial Organisms

This review, issued in two parts, describes the information on the structure and biological activity of animal alkaloids derived from polymethyleneamines and produced by marine organisms, wasps, spiders, and microorganisms. Animal alkaloids are outstanding models for developing methods and drugs for the treatment of many human diseases. In the first part, we consider compounds produced by marine and microbial organisms. Some promising synthetic analogues of these alkaloids are used in developing modern preparations for the chelate therapy of excessive blood iron content and antituberculosis, antiproliferative, and immunosuppressive drugs.     

The cholesterol lowering properties of the complex compound simvastatin with glycyrrhizic acid (simvaglyzin) in experimental models

A molecular complex of simvastatin (SV) and glycyrrhizic acid (GA) (at their ratio of 1 : 4) has been synthesized. The complex named “simvaglyzin” (SVG) was stable in aqueous and aqueous-alcohol solutions at GA concentrations exceeding 0.2 mM. In vitro SVG acted as an uncompetitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA (3-HMG-CoA) reductase (Ki of 94 nM). Appearance of this inhibitory activity is associated with cytochrome P450-dependent conversion of SVG, because the addition of 1 mM metyrapone to the incubation medium fully prevented the inhibition of 3-HMG-CoA reductase. SV and SVG (used at 300 nM concentration) inhibited mevalonate synthesis rate by 39.15±8,27 and 38.85±3,04%, respectively. In vivo SVG showed a dose-dependent cholesterol lowering effect. In rats the cholesterol lowering effect of SVG used at daily doses equivalent to 66 and 100 mg/kg of SV was the same as the effect of SV administered at the daily dose of 200 mg/kg. The decrease in total cholesterol of blood serum was 7% and 9% (p < 0.05) and 8%, respectively. Myotoxicity of these SVG doses estimated by blood serum creatine phosphokinase (CPK) activity was lower than that of SV. In rats treated with SV the activity of CPK increased by 79% (p < 0.01), while in SVG treated rats it decreased by 30% and 36% (p < 0.05). Any increase of the hepatotoxicity markers alanine aminotransferase or aspartate aminotransferase in blood serum was not observed. The data suggest pharmacological synergism attributed to the SV-GA complex formation and increased safety of the resultant complex compared with a parent compound.     

Asymmetric induction in catalyzed synthesis of organic compounds as an important stage in the evolution of life on earth

It is shown that natural chiral catalysts, which could be formed e.g., from optically active amino acids on basic natural minerals, could lead, at early stages of evolution, to the formation of rather complex optically active products from starting achiral compounds. Using biomimetic combinations of vanadium ion complexes and chiral ligands synthesized from widely occurring natural compounds, we created novel catalytic systems, permitting the transfer of optical activity in the course of catalytic chemical transformations of achiral compounds. We found that in the presence of natural clay, optically active terpenoids from the pinane series undergo multistage transformations, forming unexpected new products with preservation of optical purity.