[DEVELOPMENT OF THE QUADRIVALENT LIVE ATTENUATED INFLUENZA VACCINE INCLUDING TWO INFLUENZA B LINEAGES--VICTORIA AND YAMAGATA].

This work is devoted to the research of the live attenuated influenza vaccine (LAIV) comprising two reassortant B/USSR/60/69-based vaccine influenza viruses Victoria and Yamagata. The intranasal immunization of the CBA mice with both Victoria and Yamagata strains induced 100% lung protection against the subsequent infection with the wild-type influenza B viruses of any antigen lineage. The quadrivalent LAIV (qLAIV) comprising both reassortant influenza B viruses Victoria and Yamagata were safe and areactogenic in adult volunteers. Following qLAIV administration the immune response was achieved to both Victoria and Yamagata lineages.

[HOMOCYSTEINE AS A PROGNOSTIC MARKER OF ATRIAL REMODELING AND CLINICAL PICTURE IN PATIENTS WITH PAROXYSMAL AND PERSISTENT FORMS OF ATRIAL FIBRILLATION].

The aim of this work was to study prognostic significance of the relationship between the homocysteine level, structural/functional atrial remodeling, and clinical picture of paroxysmal and persistent forms of atrial fibrillation (AF). The study included 75 patients with AF concomitant with coronary heart disease and hypertensive disease without apparent structural changes in myocardium. Group 1 was comprised of 48 patients with paroxysmal AF, group 2 of 27 patients with persistent AF. 19 patients with coronary heart disease and hypertensive disease without AF served as controls. The structural and functional state of the heart was evaluated based on two-dimensional trans-thoracal echocardiography with the use of the formulas for calculating left ventricular characteristics. Blood homocysteine levels were measured The frequency of AF relapses was determined after an 1 year follow-up. The homocysteine level over 11.2 mcmol/l was related to left ventricle enlargement (over 40 mm), high frequency and relapse rate of AF. It is concluded that the relationship between homocysteine levels, left ventricle size, frequency and relapse rate of AF suggests the influence of homocysteine on atrial remodeling. A rise in the homocysteine level above 11 mcmol/l should be regarded as a prognostic factor of increased AF relapse rate.

[SOME ASPECTS OF NON-SPECIFIC PROPHYLAXIS AND THERAPY OF ESPECIALLY DANGEROUS INFECTIONS].

Recently, due to spread of dangerous and especially dangerous infections much attention is given to development of complex approaches to their prophylaxis and therapy. Data on use of immune modulators, cytokines, probiotics, preparations of plant origin for non-specific prophylaxis of especially dangerous infections are analyzed in the review, and expediency of their combined use with specific and emergency prophlaxis of these diseases is evaluated.

[Humoral and cell-mediated immune responses in humans to the A/California/07/ 2009 (H1N1) virus, A(H1N1)pdm2009].

During the twentieth century the world faced four influenza A pandemics: A (H1N1) in 1918, A (H2N2) in 1957, A (H3N2) in 1957 and A (H1N1) recirculation in 1977. In the beginning of 2009 the global spread of A(H1N1)pdm2009 virus was detected. In consideration of clinical evidences and genetic data analysis WHO declared as the novel pandemic of 21th century. However, the fact of exceedingly prolonged previous worldwide circulation of A (H1N1) influenza viruses was not taken into account. Further development showed epidemiological prognosis not to be accurate enough. The present work is an attempt to analyze this question from the immunological standpoint based on our studies of antibody and cellular immunity to A(H1N1)pdm2009 virus in vaccinated and non-vaccinated persons of different ages. The study results allow concluding that A(H1N1)pdm2009 is the drift variant of A (H1N1) viruses antigenically close to A/Swine/1976/1931 (H1N1). It was shown that the significant of persons have cross-reactive B and T cell immunological memory to A(H1N1)pdm2009 strain. This could be a reason of decreased A(H1N1)pdm2009 pandemic severity.

[Field of view changes after vitreomacular surgery: a treatment quality criteria].

The study enrolled 177 patients that had been admitted to the Research Institute of Eye Diseases of the Russian Academy of Medical Sciences for diagnostics and treatment - 134 patients with idiopathic macular hole and 43 patients with epiretinal fibrosis. All vitreomacular surgeries were performed between 2005 and 2011. Visual field defects were seen in all groups and were classified as either peripheral or paracentral, or concentric. The groups differed by the rate and the localization of the visual field defects. A direct relation between the severity of iatrogenic retinal damage, the extent of postoperative retinal thinning and the presence/type of visual field defects was established. Causes and risk factors of visual field loss after vitreomacular surgery have been identified and analyzed. Preventive measures for this complication have been proposed. Treatment efficacy varied depending on the causes. Acute peripheral visual field loss--"tunnel phenomenon"--as a result of significant iatrogenic local retinal damage during vitreomacular surgery has been described.

[Effect of infliximab on amino acid content in blood lymphocytes of alcohol-intoxicated rats].

Dose-dependent effects of monoclonal antibodies to tumor necrosis factor alpha (TNFa) in the form of infliximab preparation have been studied in Wistar rats upon with alcohol intoxication for 10 weeks (Lieber- De Carli liquid diet). It is established that the intraperitoneal administration of infliximab within the last 10 days of alcoholization in doses of 1 mg/kg and 10 mg/kg leads to dose-dependent changes in individual indices of the free amino acids pool and the amino acid balance in blood lymphocytes. Infliximab administered on the background of alcohol intoxication increases the pool of free amino acids and activates their metabolism in rat blood lymphocytes, which is probably due to inactivation of TNFalpha and adaptive changes in the amino acid transport system.

[Study of the heterogeneity of 16s rRNA gene and groESL operone in the dna samples of Anaplasma phagocytophilum, Ehrlichia muris, and "Candidatus Neoehrlichia mikurensis" determined in the Ixodes persulcatus ticks in the area of Urals, Siberia, and far east of Russia].

A total of 3552 Ixodes persulcatus from Sverdlovsk, Chelyabinsk, Novosibirsk, Irkutsk regions and Khabarovsk Territory were examined on the Ehrlichia and Anaplasma presence by nested PCR based on the 16S rRNA gene. Both Anaplasma phagocytophilum and Ehrlichia muris DNA were found in I. persulcatus in all studied regions. A. Phagocytophilum was detected in 1.3-6.3% of ticks and E. muris - in 2.0-14.1% of ticks. Moreover, "Candidatus Neoehrlichia mikurensis" DNA was found in 8 ticks collected in Novosibirsk, Irkutsk Regions and Khabarovsk Territory. Partial nucleotide sequences of 16S rRNA gene and groESL operone (1240-1300 bp) were determined for 65 samples of A. Phagocytophilum, 17 samples of E. muris and 4 samples of "Candidatus Neoehrlichia mikurensis". Nucleotide sequences of 16S rRNA gene and groESL operone of E. muris and "Candidatus Neoehrlichia mikurensis" were shown to be highly conservative, and nucleotide sequences of groESL operone of both E. muris and "Candidatus Neoehrlichia mikurensis" differed from the sequences found previously in other species of Ixodid tick. On the basis of analysis of the 16S rRNA gene and groESL operone sequences it was concluded that all revealed samples A. Phagocytophilum could be divided into 2 groups. GroESL operone sequences of A. Phagocytophilum from the first group were identical to each other but significantly differed from the known groESL operone sequences (less than 98.2% of similarity), whereas their 16S rRNA gene sequences were identical to the sequence of widely distributed and pathogenic for human A. Phagocytophilum genetic variant (CAHU-HGEl, GenBank AF093788) or differed from it by a single nucleotide substitution. The nucleotide sequences of groESL operone of A. Phagocytophilum from the second group differed from each other by 1-4 nucleotides and were closely related (99.2-99.4% of similarity) to the sequences of groESL operone ofA. phagocytophilum isolates found in Europe in Ixodes ricinus and roe deer. The nucleotide sequences of the 16S rRNA gene of A. Phagocytophilum from the second group were most similar to the sequence of the rare A. Phagocytophilum genetic variant previously found only in China (GenBank DQ342324).

[Neuromediator systems in the brain of rats in alcohol abstinence syndrome].

The content of key neuromediators in the brain cortex, brain stem, and thalamus was studied in rats under conditions of alcohol abstinence syndrome. At the peak of the abstinence syndrome manifestation (one day), these parts of the brain were characterized by an increase in the level of dopamine, which was normalized by the end of a one-week period of abstinence. On the third day of abstinence, there was a decrease in the content of noradrenaline in the brain stem on the background of normalization of the neurotransmission processes in the brain cortex and thalamus. Upon a one-week abstinence, the content of noradrenaline in the brain stem and cortex changed in the opposite directions.

[Effect of tritarg on proteinogenic amino acid spectrum in blood serum and lymphocytes].

Single intragastric injection of tritarg leads to different multidirectional changes in the concentration of free proteinogenic amino acids in the blood serum and lymphocytes isolated from the blood and liver. Changes in the amino acid stock of blood and liver lymphocytes were observed 3 and 24 hours after the drug injection. The changes in concentrations of individual free amino acids are more pronounced in liver lymphocytes than in blood lymphocytes. There is a decrease in the content of proteinogenic amino acids in blood serum, which may reflect the supply of these compounds to cells and is indicative of the stimulation of polypeptide and protein synthesis.

[Neurotransmitter changes in the rat brain under combined intoxication induced by alcohol and morphine]. / Neiromediatornye narusheniia v golovnom mozge krys pri ostroi kompleksnoi intoksikatsii étanolom i morfinom.

We investigated the levels of biogenic monoamines and their metabolites in the rat hypothalamus, midbrain and cerebellum in acute complex intoxication with morphine and alcohol. The distinctive features of neurotransmitter disorders in various parts of the rat brain under a single exposure to ethanol and morphine, as well as the differences between acute morphine-alcohol and alcohol-morphine intoxication were established. Complex intoxication with alcohol and morphine resulted in signs of dopamine consumption only in the hypothalamus, regardless of the order of alcohol and morphine administration. Under conditions of alcohol-morphine intoxication an increase in the level of metabolites of the serotonergic system was noted in the investigated parts of the brain. In the midbrain and cerebellum the manifestation of combined action of ethanol and morphine is mainly determined by the effect of the last of the administered substances. There are features of changes in the indices of the dopaminergic and serotonergic systems in these experimental conditions, confirmed by the processes of dopamine catabolism and a decrease in the norepinephrine and serotonin concentration in the hypothalamus, which are not observed under individual action of ethanol and morphine.

[Effect of neutrophilokines on functional activity of macrophages during formation of immunity against cholera].

AIM: To study effect of neutrophilokines on functional activity of macrophages (Mph) during formation of immunity against cholera. MATERIALS AND METHODS: In order to obtain peritoneal neutrophils (Nph), 2 ml of 0.1% glycogen solution in buffered with phosphates sodium chloride solution was administered intraperitoneally to 100 outbred mice. Vibrio cholerae 1130 in dose 10 microbial cells/Nph and cholera toxin (CT) in dose 1 or 10 mcg/ ml were used as inducers of neutrophilokines synthesis. Obtained neutrophilokines were assessed on their effect on phagocytic activity of Mph, resistance of these cells to cytotoxic and apoptogenic effects of Vibrio cholerae and CT as well as effect on lysosomal apparatus of Mph. RESULTS: It was established that neutrophilokines induced by Vibrio cholerae and CT stimulate killer activity of Mph and lability of their lysosomal membranes, and suppress programmed death of these cells. CONCLUSION: Results of studies revealed immunoregulatory activity of neutrophilokines relative to Mph and demonstrated ability for cooperation between mono- and polynuclear phagocytes mediated by cytokines and, in particular, neutrophilokines.

[Influence of neutrophilokines on population and subpopulation repertoire of lymphocytes and their functional activity during immune response against plague].

Results of experimental study of regulatory effect of nutrophilokines induced by Yersinia pestis EV strain on population and subpopulation repertoire of lymphocytes and their functional activity during immune response against plague infection are presented. It was established that these neutrophilokines stimulate CD4+ and suppress CD8+ lymphocytes. Helper effect of neutrophilokines on functional activity of lymphocytes was more pronounced during secondary than during primary immune response.

[Role of cholera toxin-induced apoptosis in alteration of macrophages in mice].

AIM: To study the role of active programmed cell death induced by Vibrio cholerae antigens in alteration of peritoneal macrophages of experimental animals. MATERIALS AND METHODS: Apoptosis was assessed by cytofluorometric analysis with propidium iodide using cytofluorometer "Coulter" as well as on characteristic morphological changes of cells in stained histological preparations. RESULTS: Performed experiments carried out by both methods provide evidence that V. cholerae and its antigens (cholera toxin, neuraminidase, chitinase, and lypopolysaccharide) cause apoptosis of mice peritoneal macrophages, which leads to their alteration. CONCLUSION: Our results demonstrate that programmed cell death of phagocytes is one of the causes of cytotoxic effect of V.cholerae and its antigens. Performed experiments show the role of apoptosis of macrophages in formation of postimmunization immunosuppression after vaccination against cholera.

[State of neuromediator systems in rat cerebellum and brain stem upon single intake of morphine].

The state of neuromediator systems in the cerebellum and brain stem was studied in rats upon acute morphine intoxication. The drug intake in a single doze of 10 mg/kg is accompanied by a decrease in the levels of dopamine, serotonin, and GABA in the cerebellum. Upon the intake of 20 mg/kg morphine, the contents of dopamine and serotonin in the cerebellum are also lower than in the untreated control, while only the first neuromediator concentration decreases in the brain stem. The administration of morphine in a doze of 40 mg/kg only reduces the level of dopamine in the cerebellum.

[Evaluation of the immunoregulatory activity of neutrophilokine fractions in a macrophage model].

A procedure was proposed to evaluate the immunoregulatory activity of neutrophilokine fractions on a model of macrophages. It was established that all the fractions studied did not affect the absorptive capacity of these cells in both primary and secondary immune responses. At the same time, the majority of neutrophilokine fractions modulated the killer activity of macrophages: they potentiated or inhibited it. The proposed procedure for evaluating the regulatory effect of individual neutrophilokine fractions on a model of studying the killer activity makes it possible not only to characterize their activity, but also to identify helper and suppressor fractions, which discloses approaches to correcting an immune response by means of these fractions.

[Preparation of fractions and characteristic of neutrophilokines complex induced by Yersinia pestis EV].

Biochemical and immunobiologic characteristics of fractions of neutrophilokines during primary and secondary immune response against plague infection are presented. Fractions were obtained using gel chromatography from neutrophilokines complex induced by vaccine strain of Yersinia pestis. It was revealed that fractions of neutrophilokines regulate IL-2 synthesis by Th1-helpers, IL-4 and IL-5 synthesis by Th2-helpers and also expression of IL-2 receptors by immunocompetent cells. Helper effect of neutrophilokines' fractions was more pronounced during secondary immune response.

[Toxicological evaluation of chronic exposure to dinil].

Experiments on rats were carried out to study the effect of dinil on the animals on chronic intake of the agent in the quantities exceeding the maximum permissible concentrations by many times. Despite few biochemical changes, there was a certain tension of adaptive processes, which appeared as a change mainly in the integral characteristics of the plasma amino acid pool. The observed changes in the levels of neurotransmitters and neuroactive amino acids in the striatum, midbrain, and hypothalamus are characterized by specific characteristics and may underlie the negative effect of dinil on central nervous system functions. Long-term administration of the agent to the animals did not induce pronounced morphological and biochemical disturbances in the tissues of the liver, heart, and kidneys. Changes in the concentrations of serotonin and neuroactive amine acids in the brain regions might have the greatest consequences to the body. Since the detectable changes in a number of metabolites are likely to be functional in the given period (monthly dinil use), an attempt to correct developing disorders with metabolic therapy agents may be recommended.

[Effect of taurine on the pool of central neuroactive compounds during ethanol withdrawal syndrome].

Influence of taurine on the pool of central neuroactive compounds during alcohol withdrawal syndrome has been investigated. Alcohol withdrawal syndrome was accompanied by a pronounced dysbalance in the formation of the pool of neuroactive compounds. The most remarkable changes were found in the levels of markers related to the central serotoninergic system, as well as dopaminergic system. Taurine administration in a dose of 650 mg/kg (i.g.) one hour before decapitation during ethanol withdrawal syndrome alleviates disturbances in the functioning of serotoninergic and (to a lesser extent) dopaminergic systems and improves the ratio of inhibitory and excitatory mediator amino acids.

[Actinomycete growth in conditions of low moisture].

Actinomycete communities demonstrated a replacement of the generic composition in time as a function of soil moisture. Representatives of the genera Streptomyces, Micromonospora, Actinomadura, Saccharopolyspora, and Microbispora were repeatedly isolated from soil under different moisture conditions (field capacity, maximum molecular capacity, and maximum adsorption capacity). Representatives of some rare genera (Thermomonospora and Kibdelosporangium) were isolated from soil with low moisture levels inhibiting growth of more hydrophilic actinomycetes and bacteria. Spores of some actinomycetes could grow at low relative air humidity (RH) (50 and 67%). The complete growth cycle of all actinomycetes starting from spore germination to sporulation was observed only at RH of 98%.

Impact of Steroids on the Inflammatory Response after Ischemic Acute Kidney Injury in Rats.

Inflammation plays a crucial role in acute kidney injury (AKI). The current study was designed to analyze the influence of prednisolone treatment on the inflammatory reaction during the first 96 h after AKI induction in a rat model. AKI was induced by unilateral clipping of the renal vessels. The treatment group received prednisolone 5 mg/kg s.c. daily. Infiltration rates of macrophages, leukocytes, and T-cells (24, 96 h) as well as plasma concentrations of the inflammatory markers intercellular adhesion molecule, interleukin-1 beta (IL-1ß), IL-18, IL-6, and tumor necrosis factor-alpha (0, 6, 24, 96 h) were determined by fluorescence-activated cell sorting (FACS) analysis only. Ninety-six hours after AKI induction, the prednisolone group demonstrated significantly lower creatinine concentrations compared to the control group (P < 0.05). Twenty-four hours after induction of AKI, a significantly higher rate of infiltrating leukocytes was detectable with FACS analysis in the control group (P < 0.01) with a corresponding significantly higher rate of macrophages after 96 h (P < 0.01). IL-6 and IL-1ß demonstrated a peak after 6 h with a significantly higher release in the control group (IL-6: P < 0.01; IL-1ß: P < 0.05). In contrast to the control group, the prednisolone group demonstrated no further incline of IL-18 after 24 h. The results demonstrate the importance of stretching the observation period in an ischemia-reperfusion-induced AKI setting beyond the first 24 h. Despite the demonstrated protective effects of a continuous prednisolone application, it seems that this single anti-inflammatory agent will not be able to completely suppress the inflammatory response after an ischemia-reperfusion-induced AKI.