[Endotoxin tolerance of mice to the effect of lipopolysaccharide and lipopolysaccharide-mice toxin complex of virulent strain Yersinia pestis 231].

AIM: Comparative study of the effect of endotoxin tolerance of mice to the effect of lipopolysaccharide (LPS37) and complex of lipopolysaccharide with mice toxin (LPS37-MT) of a virulent Yersinia pestis 231 strain. MATERIALS AND METHODS: Preparations of LPS of highly virulent strain Y. pestis 231 obtained by phenol method from cells cultivated at 37 degrees C as well as commercial preparations of S-LPS and R-LPS of Escherichia coli were used. Mice toxin was isolated from vaccine strain Y. pestis EV76. Effect of endotoxin tolerance was determined in mice treated with aminosugar D-galactosamine. RESULTS: The effect of initial LPS37 and modified form LPS37-MT of Y. pestis 231 was established to significantly differ from each other. When Y. pestis LPS37 is combined with heterologous forms--E. coli LPS or Y. pestis LPS37-MT, the inflammatory response of the organism differs and varies from complete or partial tolerance to complete lack thereof. For LPS37-MT complex only the sequence of administration to bioassay animals of LPS preparations is principal. In the case when primary activation is carried out by LPS37-MT and secondary--by Y. pestis LPS37 or S- and R- forms of E. coli LPS--the tolerance effect is absent. On the contrary, if LPS37-MT is used for recurrent activation against the background of all the other LPS forms including Y. pestis 231 LPS37 the inflammatory response is completely suppressed. CONCLUSION: Tolerance of mice to effect of LPS and LPS-MT complex of virulent Y. pestis 231 strain was shown to be different.

Structural and theoretical study of π-stacking interactions in new complexes based on CuCl2 and 3-sulfonamide-substituted imidazo[2,1-b]thiazoles.

CONTEXT: At present, sulfonamides and their metal complexes have received a new impetus for development. Of particular interest is the study of molecular and crystal structures, which takes into account weak non-valent interactions. Despite the low energy of such interactions, in many cases, they act collectively, and the sum of their actions can play a significant role. As a result, the spectrum of medical and biological activity of new metal complexes is expanded. In this regard, the synthesis and study of the molecular and crystal structure of sulfonamides and their metal complexes is of undoubted relevance. In this work, we studied non-valent intra- and intermolecular interactions in ligands of sulfonamide-substituted imidazo[2,1-b]thiazoles and their previously unknown complexes with CuCl2. The performed analysis of the data obtained by X-ray diffraction analysis made it possible to establish the intramolecular π-stacking interaction in imidazothiazole ligands, which is retained in their complexes with CuCl2. Within the framework of QTAIM topological analysis of electron density and DORI analysis, stereoelectronic and topological structures were studied. In the complexes, tetral, chalcogen, and pnycogen new interligand non-valent interactions were established. The energies of all established types of non-valent interactions have been calculated, and their comparative evaluation has been made. METHODS: X-ray data of new arylsulfonylamino-substituted derivatives of imidazo[2,1-b]thiazoles and their metal complexes with CuCl2 have been studied. To determine the theoretical prerequisites for the occurrence of π-stacking in the molecules under study, the QTAIM method was used in the framework of the DFT/B3LYP/6-311 + G(d) calculation using the GAUSSIAN 09 program. In addition, the DORI electron density region overlap indicator and the Multiwfn program were used to analyze non-valent interactions.

[Toxicity and cytokine-inducing activity of lipopolysaccharide of virulent Yersinia pestis 231 strain].

AIM: Determine correlation between toxicity and cytokine inducing activity of parent and conformation modified forms of lipopolysaccharides (LPS) of virulent Yersinia pestis strain. MATERIALS AND METHODS: LPS was isolated by phenol method from Y. pestis 231 cells grown at 37 degrees C (LPS37). LPS37 was modified by "mice" toxin (MT) Y. pestis. Toxicity was controlled in mice. TNFalpha and IFNgamma cytokine production was determined by enzyme immunoassay. The study was performed in human monocytes U-937 cell line. TLR4 re-stimulation was performed after activation of monocytes by S-LPS and R-LPS of Escherichia coli. RESULTS: LPS37 conformation change of virulent Y. pestis 231 strain during formation of complex with "mice" toxin increases its toxicity for animals by 2 times. LPS37 and LPS37-MT induce TNFalpha and IFNgamma synthesis by human monocytes. LPS37 simultaneously activates MyD88-dependent as well as MyD88-independent signal pathways. Modified LPS37-MT form is a strong activator only of MyD88-dependent pathway and thereafter induces synthesis of predominately one of the cytokines--TNFalpha. Monocyte response to primary and recurrent activation by LPS37 and LPS37-MT corresponds to R- and S-LPS E. coli cytokine response profile. CONCLUSION: A direct correlation between toxicity of LPS37 and LPS37-MT and their TNFalpha-inducing activity was demonstrated in the study. LPS37 and LPS37-MT of Y. pestis 231 differentially activates TLR4 signal pathways of human monocytes.

[Toxicity of Yersinia pestis EV76 lipopolysaccharides for mice sensitized by D-galactosamine].

AIM: To study toxicity of lipopolysaccharides (LPS28 and LPS 37) of Yersinia pestis for mice sensitized by D-galactosamine (D-GalN). MATERIALS AND METHODS: LPS were obtained by the Westphal method from Y. pestis EV76 strain grown at temperatures of 28 and 37 degrees C. Dexamethasone and pentoxifylline were used as immunodepressants. Uridine was used for interruption of D-GalN effect. RESULTS: It was revealed that administration of D-GalN to mice increased their sensitivity to LPS of Y. pestis. Maximal increase in LPS toxicity was observed after simultaneous administration of D-GalN and LPS. D-GalN in dose 20 mg per mouse determined 100% lethality of animals during 24 h after administration of 10 mcg of LPS28 and 25 mcg of LPS37. Uridine in dose of 20 mcg per mouse administered 1 h after LPS and D-GalN neutralized effect of LPS in the presence of D-GalN. Dexamethasone and pentoxifylline did not protect animals sensitized by D-GalN against lethal effect of Y. pestis LPS. CONCLUSION: It was found experimentally that D-GalN enhances toxic effect of LPS28 in hundreds of times, and non-toxic LPS37 of Y. pestis EV76 demonstrated toxicity comparable to LPS28. Thus the D-GalN model could be used for enhancement of laboratory animals sensitivity to effect of Y. pestis LPS.

[Cryostabilization of biological properties of plague phages]. / Kriostabilizatsiia biologicheskikh svoistv chumnykh fagov.

Conditions of cryostabilization of Yersinia pestis phages preserving their biological properties at very low temperature are studied.

[Evaluation of antiepileptic effects of cortexin in a model of convulsions].

We studied antiepileptic effects of cortexin administered in doses 0,015, 0,15 and 1,0 mg/kg intraperitoneally in solution or intranasally in the complex with nanoparticles in a model of acute and chronic convulsions in rats induced by pentylenetetrazole. In the model of epileptic status, the long-term preliminary administration of cortexin had no effect on convulsions while in the model of chronic convulsions (temporal epilepsy), cortexin had a marked dose-dependent antiepileptic effect. The influence of cortexin on neuroplasticity and its clinical potential are discussed.

Polyelectrolyte multilayered nanofilms as a novel approach for the protection of hydrogen storage materials.

This work describes the encapsulation of hydrogen storage materials from organic solvents. Due to complex formation the shell provides stability and selective permeability. Specifically, sodium borohydride particles were encapsulated within polymer films by the layer-by-layer self-assembly of oppositely charged polyelectrolytes (polyethyleneimine and poly(acrylonitrile-co-butadiene-co-acrylic acid)). The polymer nanofilm fabrication was performed using dichloromethane as a working media. IR spectroscopy was applied to investigate the chemical interaction between the polyelectrolytes. The multilayer film preparation was verified by Z-potential measurements, scanning electron microscopy, and confocal laser microscopy. The stability of sodium borohydride protected with a polyelectrolyte shell was increased compared to that of the pure material under ambient conditions.

[Polyelectrolyte microcapsules as systems for delivery of biologically active substances].

Novel biodegradable microcapsules for delivery of biologically active substances (BAS) were prepared by layer-by-layer (LbL) adsorption of oppositely charged polyelectrolytes, namely sodium alginate (Alg) and poly-L-lysine (PLL). To immobilize these BAS, porous spherical CaCO3 microparticles were used as templates. The templates (cores) were coated with several layers of oppositely charged polyelectrolytes forming shell on a core surface. The core-shell microparticles were converted into hollow microcapsules by a core dissolution after an EDTA treatment. Mild conditions for microcapsule fabrication allow to perform an entrapment of various biomolecules while keeping their bioactivity. Biocompatibility and biodegradable capability of the polyelectrolytes give a possibility to use the microcapsules as the target delivery systems. Chymotrypsin (Chym) entrapped into the microcapsules was used as a model enzyme. The immobilized enzyme was found to keep about 86% of the activity compared to a native Chym. The obtained microcapsules were stable at an acidic medium while they could be easily decomposed by trypsin treatment at an slightly alkaline medium. Chym was shown to be active after being released from the microcapsules decomposed by trypsin treatment. Thus, the microcapsules prepared by the LbL - technique can be used for the development of new type of BAS delivery systems in humans and animals.

[Entrapment of herbal extracts in biodegradable microcapsules].

The microcapsules with entrapped herbal water-soluble extracts Plantago major and Calendula officinalis L. (HE) were prepared by LbL-adsorption of carrageenan and modificated chitosan onto CaCO3 microparticles with their subsequent dissolving after the treatment of EDTA. Entrapment of HE was performed by adsorption and co-precipitation techniques. The co-precipitation provided better entrapment of HE compared to adsorption. In vitro release kinetics in an artificial gastric juice (AGJ) was studied. The HE release was shown to accelerate gastric ulcer treatment in a rat model.