[Clinical factors and response to therapy with disease-modifying drugs for multiple sclerosis: the experience of the Tomsk region]. / Klinicheskie faktory i otvet na terapiyu preparatami, izmenyayushchimi techenie rasseyannogo skleroza: opyt Tomskoi oblasti.

OBJECTIVE: To investigate a disease-modifying drugs (DMD) response in multiple sclerosis (MS) in the Tomsk region population and detect clinical factors associated with the treatment response. MATERIAL AND METHODS: A 5-year prospective clinical study included 363 MS patients of the Tomsk region taking DMDs of the «first-line¼ and «second-line treatments¼. The response to DMDs therapy and the impact of MS clinical characteristics on response to treatment were assessed. RESULTS: Clinical factors associated with resistance to DMD are male gender, partial reduce of the MS onset symptoms, short period of the first remission, severe neurological impairment, high relapse rate and disease progression rate. CONCLUSION: Clinical features of MS are crucial factors associated with DMD response and should be used to prescribe DMD. This factor assessment can improve efficacy of the personalized MS treatment.

[BDNF gene RS6265 polymorphism in patients with multiple sclerosis of Tomsk region]. / Polimorfizm RS6265 gena BDNF v populyatsii bol'nykh rasseyannym sklerozom Tomskoi oblasti.

OBJECTIVE: To study the effect of the RS6265 polymorphism of BDNF gene on the risk of development, main clinical characteristics and DMT response in MS patients in Tomsk region. MATERIAL AND METHODS: The study group included 321 patients, the control group consisted of 266 healthy volunteers. Deoxyribonucleic acid (DNA) was isolated from venous blood using the standard phenol-chloroform method. Genotyping was carried out by real-time polymerase chain reaction (PCR) using competing TaqMan probes complementary to the polymorphic nucleotide sequence. RESULTS: Carriage of the C allele and CC genotype of the RS6265 polymorphism of the BDNF gene was found to be a factor determining a more favorable MS course. CONCLUSION: Carriers of the indicated genotype had a low rate of MS progression, a lower frequency of relapses and a less pronounced degree of disability with a comparable MS duration, and significantly more often demonstrated a more optimal response to first and second line of DMT.

[Adjuvant effect of dispersed fullerene C60 on the immune response to constructs harboring amino acid and nucleotide sequences of hepatitis C virus nonstructural NS5B protein].

INTRODUCTION: A vaccine against hepatitis C has not yet been developed. Recombinant proteins and plasmids encoding hepatitis C virus (HCV) proteins, the components of candidate vaccines, induce a weak immune response and require the use of adjuvants. The aim of the work was to study the adjuvant action of an aqueous solution of fullerene C60 during immunization of mice with HCV recombinant protein NS5B (rNS5B) that is an RNA-dependent RNA polymerase, or with NS5B-encoding pcNS5B plasmid. MATERIALS AND METHODS: An aqueous solution of dispersed fullerene (dnC60) was obtained by ultrafiltration. C57BL/6 mice were immunized with rNS5B subcutaneously, pcNS5B intramuscularly mixed with different doses of dnC60 three times, then the humoral and cellular response to HCV was evaluated. RESULTS: Mice immunization with rNS5B in a mixture with dnC60 at doses of 250 g/mouse significantly induced humoral response: a dose-dependent increase in IgG1 antibody titers was 720 times higher than in the absence of fullerene. There was no increase in the cellular response to rNS5B when administered with dnC60. The humoral response to DNA immunization was weak in mice of all groups receiving pcNS5B. The cellular response was suppressed when the plasmid was injected in a mixture with dnC60. CONCLUSIONS: Dispersed fullerene dnC60 is a promising adjuvant for increasing the immunostimulating activity of weakly immunogenic proteins including surface and other HCV proteins, important for a protective response. Further research is needed to enhance the ability of dnC60 to boost the cellular immune response to the components of the candidate vaccine.

Protective Properties of Lanthanum Nitrate against Pathogens with Various Morphological and Functional Properties.

Dose-dependent protective effects of lanthanum nitrate solution and gel were shown on the model of experimental infection caused by a virulent strain of Shigella flexneri 2a or opportunistic bacteria Klebsiella pneumoniae in outbred and DBA mice.

Effects of Miramistin and Phosprenil on Microbial Biofilms.

Effects of Miramistin and Phosprenil on biofilms of S. pyogenes, S. aureus, E. coli, L. acidophilus, and L. plantarum were studied. Significant differences in the effects of these substances on mature biofilms of microorganisms and the process of their formation were observed. Miramistin had significant inhibiting effects on the forming of biofilms and on the formed biofilms of all studied microorganisms. Treatment with Miramistin inhibited biofilm formation by 2-3 times compared to the control. This effect was found already after using of Miramistin in the low doses (3.12 µg/ml). Inhibition of the growth of a formed biofilm was observed only after treatment with Miramistin in the high doses (25-50 µg/ml). Phosprenil in the high doses (15-30 mg/ml) inhibited the forming of biofilms, especially the biofilms of S. pyogenes and L. plantarum (by 3-4.5 times). Treatment of formed biofilms with the agent in doses of 6.0 and 0.6 mg/ml was associated with pronounced stimulation of its growth in S. pyogenes, S. aureus, and L. acidophilus.

[Some aspects of underground organs of spotleaf orchis growth and phenolic compound accumulation at the generative stage of ontogenesis].

For the first time, the time courses of the growth and accumulation of phenolic compounds (PHCs) in different parts of the organs of the underground organs of the tuberoid orchid Dactilorhyza maculata during vegetation and the winter dormancy period were studied. It was shown that the replacement of old tuberoids and adventitious roots by new ones is accompanied by active growth, photosynthate redistribution, and PHC accumulation. It was found that the tuberoid performing the function of a storage organ possessed a low PHC content, which increased at the end of vegetation and was stably high during the winter dormancy period; in spring the content decreased, most likely as a result of PHC catabolism and utilization for growth processes. It was proposed that the higher PHC content in adventitious roots and tuberoid terminal parts is determined by mycotrophy of the organs.

["Non-immune" interactions of gamma-globulin in regulation of immune reactions].

It was shown using the model of L2-dependent proliferation of T-cells that IL2 forms complexes with gamma-globulin inhibiting IL2 activity. In this interaction IL2 acts as lectin binding with two-antenna terminals of 5 or 6 mannose residues in one and the same region of immunoglobulin. Similar effect is observed in vivo in case of induction of DTH to listerial antigens. This phenomenon accounts for suppression of the immune response after passive injection of autoantibodies and for the inverse relationship between humoral and cellular immunity. Reduction of IL2 activity after its interaction with IgG or immune complexes may be regarded as a universal feedback immunoregulatory mechanism. External and internal factors showing affinity to mannose, e.g. sodium polyprenyl phosphate or lactobacillus, can interfere with this process and exert immunomodulating effect.

[Lactobacillus plantarum and phosprenyl competitively distinguish ovalbumin oligomannoside n-glycan].

AIM: Demonstration of the ability of native products of lactobacteria to bind mannose containing N-glycans as a display of one of the mechanisms of probiotic behavior of these symbiont microorganism in gastrointestinal tract (GIT). MATERIALS AND METHODS: Lactobacillus plantarum 30 grown on selective medium (MRS-agar) and their ultrasound lysates were used in the study. Standard technique of delayed type hypersensitivity (DTH) reaction was used with inactivated Listeria monocytogenes culture as a priming agent. RESULTS: DTH reaction in vivo has demonstrated that oligomannoside N-glycan of egg albumin is a general acceptor for adhesins that are present in the native preparations of certain L. plantarum strains, as well as for phosprenyl (PHP) immunomodulator--an inhibitor of cell IL-2 reception. CONCLUSION: The data obtained give evidence that mannose specific adhesins that are conserved in lactobacteria preparations have the same binding sites in egg albumin as PHP and, therefore, IL-2.

Mouse splenocyte blast transformation in the presence of plasma γ-globulin fraction proteins and their complexes with copper and zinc.

Plasma γ-globulin fraction proteins, copper and zinc cations, and metal complexes formed by these cations and human serum γ-globulin induce blast transformation of splenocytes from BALB/c mice at a level comparable to that induced by concanavalin A. Zinc bound to γ-globulin reduces by 25% and copper in complex with this protein stimulates by 1.6 times its capacity to induce blast transformation. Combinations with concanavalin A reproduce the effects of γ-globulin-metal complex under conditions of mitogen induction. Incorporation of(3)H-thymidine in splenocytes incubated with combinations of γ-globulin-copper metalcomplex, copper cations, and control protein with concanavalin A was by 1.4, 1.3 (p<0.1), and 1.25 times higher (p<0.05), respectively, than after incubation with concanavalin A alone.

Heart rate variability in kittens during early postnatal ontogeny.

Heart rate variability in awake kittens under resting conditions was studied during the following periods of postnatal ontogeny: newborn animals, 10-day-old animals (eye opening), 20-day-old animals (rise on the legs), and 30-day-old animals (control). Newborn animals were characterized by high activity of the sympathoadrenal system due to birth stress. The effect of stress factors increased in 10-day-old kittens, which was related to the start of functioning of distant receptors and delivery of new environmental information into the brain. The acquisition of upright posture and locomotion on the limbs were accompanied by activation of the vagus nerve in kittens. Significant changes in temporal, geometric, and spectral characteristics illustrate an increase in adaptability of the organism and possibility for independent living (particularly, by the 30th day of life).

[Influence of bacteria of Lactobaccilus genera on cytotoxic activity of splenocytes in experimental animals].

Influence of lactobacilli on cytotoxic activity of splenocytes from mice of CBA line was studied in vivo and in vitro (after cultivation of splenocytes with chloroform-killed bacteria, homologous lysates obtained by ultrasound, and with native filtrates). Data on increase of splenocytes cytotoxic functions induced by lactobacilli has been obtained. Mechanisms of lactobacilli-mediated activation of cellular factors of antitumor immunity (cytotoxic lymphocytes and natural killers) were discussed. Information on the ability of cell wall components, cytoplasmic fractions, and substances secreted by lactobacilli to stimulate the immune response of a microorganism is presented.

[Influence of Lactobacillus on the migration activity of macrophages].

Influence of Lactobacillus on the migration activity of intact macrophages during their cultivation with serum and supernatant of cells from Peyer's patches and spleen that were obtained from mice of CBA line orally sensibilized with lactobacteria was studied. Data about stimulation of production of factor inhibiting migration of macrophages by immunocompetent cells and development of delayed-hypersensivity reaction are obtained. Mechanisms of complex influence of lactobacteria on cell factors of innate and adaptive immunity are discussed.

[The influence of bacteria of the Burkholderia cepacia and Pseudomonas aeruginosa complex on cell-mediated immune reactions in experimental animals].

The evidence has been obtained that various species, as well as individual strains having pathogenicity factors, produced different effect on the functional activity of immunocompetent B and T lymphocytes of mice infected intraperitoneally. The injection of live P. aerruginosa PA 103 and B. cepacia 8240 cells resulted in imunosuppression of antibody-forming cells, synthesizing antibodies to heterologous antigens. On the contrary, in the animals infected with B. cepacia 8236 the functional activity of B lymphocytes increased. An increase in the proliferative activity of spleen cells was noted in the presence of T and B mitogens after the infection of mice with P. aeruginosa PA 103 in comparison with B. cepacia 8236 and B. cepacia 8240 which produced a faintly pronounced modulating effect. The pathogenesis mechanisms of infections induced by these microorganisms as well as the development of chronic, persisting forms of the infectious process are discussed.

[The effects of the microbial components of the probiotic Acilact on the cell-mediated immunity factors under experimental conditions].

The authors analyzed the effects of the microbial components of the probiotic Acilact on the cell-mediated factors of the immune homeostasis. According to the results, L. acidophilis stimulates the functional activity of immunocompetent cells, especially T-cell mediated immunity with strain- and dose-depending differences in intensity. The study demonstrated the ability of L. acidophilis to activate expression of the genes of pro-inflammatory cytokines (IFNgamma, IL-6, 12, and TNFalpha), to induce production of IFNalpha and IFNgamma, and increase interferon production, with additional stimulation of lymphoid organ cells with specific inductors in vitro. The study established that L. acidophilis stimulates production of macrophage migration inhibition factor by immunocompetent cells of Peyer's plaques and the splen, and induces its quantitative increase in the serum of CBA mice. The study detected immunocorrecting effect of L. acidophilis by the example of experimental shigellous infection, demonstrated intensification of the prolipherative activity of immunocompetent T-cells, induction of the expression of the genes of pro-inflammatory cytokines (IFNgamma, IL-1beta, 6, 12, and TNFalpha), but not IL4 and 10, increase of synthesis of IFNalpha and IFNgamma by the cells of Peyer's plaques, the splen and thymus. The obtained results prove the immunological effect of the probiotic preparation Acilact, based on the strains L. acidophilis NK1 and L. acidophilis K3(111)24.

[Immunostimulating and anti-carcinogenic activity of the normal intestinal lactoflora]. / Immunostimuliruiushchaia i antikantserogennaia aktivnost' normal'noi laktoflory kishechnika.

One of major functions of lactic acid bacteria is their participation in the formation of local and systemic immune resistance of the host. The lactic acid bacteria associated with the mucous coat of the gastro-intestinal tract are cooperating with epitheliocytes, M-cells of Peyer's patches and various cells of the immune system. As a result of processing and presentation of specific cell components, lactic acid bacteria use mechanisms of modulation of cell-dependent immune response, activate RES and stimulate cytokine production. The article gives data on the role of lactic acid bacteria in the formation of T-and B-cell immune response, production of pro-inflammatory and anti-inflammatory cytokines ensuring the balance between humoral and cell-dependent immunity. The mechanisms of antitumor and oncostatic activity of lactic acid bacteria are analyzed. The polyfunctional influence of lactic acid bacteria on the immune reactions of the macroorganism includes the enhancement of the activity of monocyto-macrophages, natural killers and cytotoxic lymphocytes, modulation of reactions of the T- and B-cell immune responses, i.e. the complex system of interaction being formed between the indigenous intestinal microflora and the macroorganism is the basis of the normal function of its immune system.

[The activity of a specialized city medical-and-social center for schoolchildren]. / O deiatel'nosti spetsializirovannogo gorodskogo mediko-sotsial'nogo tsentra dlia shkol'nikov.

Described in the paper is a concept of an alternative educational facility (City center for medical, psychological and social follow-up, diagnosis and consultation of schoolchildren in Yaroslavl) popularizing the healthy mode of life among pupils of general schools. The center's experts developed and tested comprehensive approaches to teaching the motivation and skills of the healthy mode of life through the comprehensive training of pupils, teachers and parents.

[Immunomodulating effect of protein fractions isolated from bifidobacteria]. / Immunomoduliruiushchii éffect belkovykh fraktsii, vydelennykh iz bifidobakterii.

The screening of the immunomodulating activity (IMA) of different protein fractions isolated from bifidobacteria was carried out and the capacity of these fractions for changing the proliferative activity of immunocompetent cells was evaluated. Soluble proteins were extracted from lyophilized and sonicated bacterial mass of B. bifidum strain 1 in Na2HPO4 (pH 8) in a water bath at 65 degrees C for 30 minutes. After the formation and removal of nucleic acid sediment the resulting supernatant fluid was dialyzed, its adsorption spectra were analyzed and the fluid was fractionated in a specially proposed device for preparative electrophoresis. Protein fractions were tested for IMA on spleen cells of CBA mice in the reaction of lymphocyte blast-transformation by the level of the inclusion 3H thymidine. The analysis of IMA of protein fractions revealed that their high-molecular components produced a pronounced dose-dependent effect on the proliferative activity of spleen cells. The fractions containing low-molecular components were either inactive (fraction 4) or active only in the maximum dose (fraction 5).

[Development of the controlled model of persisting infection , caused by Pseudomonas aeruginosa and bacteria of the complex Burkholderia cepacia]. / Razrabotka upravliaemoi modeli persistiruiushchei infektsii, vyzvannoi Pseudomonas aeruginosa i bakteriiami kompleksa Burkholderia cepacia.

As the result of testing three different variants, the experimental models of persisting infection for P. aeruginosa and B. cepacia have been developed. These doses differ in the time of administration, doses of antibiotics and the infective doses of the microorganisms. The administration of the sub-inhibiting concentration of antibiotics for 5 days and the subsequent infection of laboratory animals (non-inbred mice) B. cepacia strains in a dose of LD50 leads to a considerable increase in the survival rate of mice and to a longer period (up to 20 days) of obtaining inoculative material from the spleen. The isolated cultures are characterized by a sharply slower growth on artificial culture media (up to 5-7 days as compared with 24-48 hours for the initial culture). The newly developed models have made it possible to control different stages of the infectious process in the induced increase or decrease of the virulent properties of the infective agent and in changes in the immune status of the host. As the result of these studies, in some mice (10%) infected with B. cepacia after the injection of gamma-hydroxybutyric acid lactone the infection has taken the acute form, while in the mice infected with P. aeruginosa no such effect has been observed. On the contrary, in the mice infected with P. aeruginosa and then receiving cyclophosphamide the transition of the infection into the acute form has been observed in 30% of the animals. In the mice infected with B. cepacia no such effect has been noted after the injection of this preparation. Different effects produced by cyclophosphamide and lactone are discussed from the positions of "quorum sensing" in pathogenic bacteria.