Amino Acids as Regulators of Cell Metabolism.

In this review, we discuss the principles of regulation and synchronization of metabolic processes in mammalian cells using a two-component model of cell metabolism consisting of a controlling signaling system that regulates major enzymatic cascades and executive metabolic system that directly performs biosynthetic reactions. This approach has allowed us to distinguish two transitional metabolic states (from catabolism to anabolism and vice versa) accompanied by major rearrangements in the signaling system. The signaling system of natural amino acids was selected, because amino acids are involved in both signaling and executive metabolic subsystems of general cell metabolism. We have developed a graphical representation of metabolic events that allowed us to demonstrate the succession of processes occurring in both metabolic subsystems during complete metabolic cycle in a non-dividing cell. An important revealed feature of the amino acid signaling system is that the signaling properties of amino acid are determined not only by their molecular structure, but also by the location within the cell. Four major signaling groups of amino acids have been identified that localize to lysosomes, mitochondria, cytosol, and extracellular space adjacent to the plasma membrane. Although these amino acids groups are similar in the composition, they have different receptors. We also proposed a scheme for the metabolism regulation by amino acids signaling that can serve as a basis for developing more complete spatio-temporal picture of metabolic regulation involving a wide variety of intracellular signaling cascades.

[Bacterial Translocation from Intestine: Microbiological, Immunological and Pathophysiological Aspects].

Bacterial translocation (BT) is both pathology and physiology phenomenon. In healthy newborns it accompanies the process of establishing the autochthonous intestinal microbiota and the host microbiome. In immunodeficiency it can be an aethio-pathogenetic link and a manifestation of infection or septic complications. The host colonization resistance to exogenous microbic colonizers is provided by gastrointestinal microbiota in concert with complex constitutional and adaptive defense mechanisms. BT may be result of barrier dysfunction and self-purification mechanisms involving the host myeloid cell phagocytic system and opsonins. Dynamic cell humoral response to microbial molecular patterns that occurs on the mucous membranes initiates receptorsignalingpathways and cascade ofreactions. Their vector and results are largely determined by cross-reactivity between microbiome and the host genome. Enterocyte barriers interacting with microbiota play leading role in providing adaptive, homeostatic and stress host reactivity. Microcirculatory ischemic tissue alterations and inflammatory reactions increase the intestinal barrier permeability and BT These processes a well as mechanisms for apoptotic cells and bacteria clearance are justified to be of prospective research interest. The inflammatory and related diseases caused by alteration and dysfunction of the intestinal barrier are reasonably considered as diseases of single origin. Maternal microbiota affects theformation of the innate immune system and the microbiota of the newborn, including intestinal commensal translocation during lactation. Deeper understanding of intestinal barrier mechanisms needs complex microbiological, immunological, pathophysiological, etc. investigations using adequate biomodels, including gnotobiotic animals.

[Microbiotic factor influencing the mononuclear phagocyte system development].

Mononuclear-phagocyte system plays an important role in natural immunity and nonspecific resistance reactions of the organism against infection. The experimental studies using conventional laboratory animals with uncontrolled microflora have certain limitations to fully appreciate the role of autoflora (microbiota) in both development and functional activity of mononuclear-phagocyte system. In the present review of the author' systemic studies the value of microbiologically controlled animals (gnotobiotes) showing the multifaceted role of microbial factor on various manifistations of mononuclear-phagocyte system including phagocytic activity of the cells of both ageing aspects and pathology conditions (inflammation, burns), influence on the colonization resistance and barrier function against translocations of microorganisms from the intestines, temperature reactions and other host defense mechanisms to infection are demonstrated. In a complex body defence, activity of both cellular and humoral factors is being stimulated and modulated by microbiotic factor. Gnotobiotic modeling approach is prospective one for modeling and analysis of molecular and cellular mechanisms in an assessment of the "host-microbiota" interactions, evaluating the effectiveness of new probiotic candidates and further microbial control development in the clinical settings.

[Gnotobiology in modern bio-medical research].

An overview of the present status and prospects of gnotobiology along with a role of normal microflora studied using laboratory animals with controlled microflora (gnotobiotes) is presented. The principal elements of gnotobiotechnology as well as possibilities of its using in both experimental and clinical investigations are analyzed. A multifaceted role of normal microflora in the host physiology and pathology prejudge the increasing importance of gnotiological models in various fields of biology and medicine, such as the development of new generations probiotics. An assessment and characteristics of selected microbial strains, host-microbe interactions etc. An organization of further complex gnotobiotic research is of prospective value.

Effect of glycine on the microcirculation in rat mesenteric vessels.

Model experiments on biomicroscopy of mesenteric microvessels in laboratory rats were performed to evaluate the effect of natural metabolites (e.g., amino acid glycine) on the microcirculation. The effect of glycine was determined from a change in the diameter of arterioles. Application of glycine (0.1 ml, 1 M) to the mesenteric surface was followed by arteriolar dilation (by 50-80%). Histamine-induced disturbances in the microcirculation were not observed after preapplication of glycine. Under these conditions, pretreatment with histamine was accompanied by reversible changes. Our results suggest that the natural metabolite glycine has a prophylactic and therapeutic effect on microcirculatory disturbances, which are induced by inflammatory-and-allergic mediator histamine.

Effect of glycine on microcirculation in pial vessels of rat brain.

Single application of glycine in a final dose of 40 mg/kg to the surface of the parietal area of rat brain produced a potent vasodilatory effect. The diameter of arterioles increased to 250% from the baseline level 1-3 min after treatment. These changes persisted for 5-10 min. In the follow-up period the diameter of vessels progressively decreased to the baseline level. Repeated application of glycine in the same dose also induced dilation of arterioles. Application of physiological saline under similar conditions did not produce these changes.

Monoassociation with Lactobacillus acidophilus UFV-H2b20 stimulates the immune defense mechanisms of germfree mice

Probiotics are formulations containing live microorganisms or microbial stimulants that have some beneficial influence on the maintenance of a balanced intestinal microbiota and on the resistance to infections. The search for probiotics to be used in prevention or treatment of enteric infections, as an alternative to antibiotic therapy, has gained significant impulse in the last few years. Several studies have demonstrated the beneficial effects of lactic acid bacteria in controlling infection by intestinal pathogens and in boosting the host's nonspecific immune response. Here, we studied the use of Lactobacillus acidophilus UFV-H2b20, a lactic acid bacterium isolated from a human newborn from Viçosa, Minas Gerais, Brazil, as a probiotic. A suspension containing 108 cells of Lactobacillus acidophilus UFV-H2b20 was inoculated into groups of at least five conventional and germfree Swiss mice to determine its capacity to stimulate the host mononuclear phagocytic activity. We demonstrate that this strain can survive the stressing conditions of the intestinal tract in vivo. Moreover, the monoassociation of germfree mice with this strain for seven days improved the host's macrophage phagocytic capacity, as demonstrated by the clearance of a Gram-negative bacterium inoculated intravenously. Monoassociated mice showed an undetectable number of circulating E. coli, while 0.1 percent of the original inoculum was still present in germfree animals. Mice treated with viable or heat-killed Lactobacillus acidophilus UFV-H2b20 presented similarly improved clearance capacity when compared with germfree controls. In addition, monoassociated mice had twice the amount of Kupffer cells, which are responsible for the clearance of circulating bacteria, compared to germfree controls. These results suggest that the L. acidophilus strain used here stimulates a nonspecific immune response and is a strong candidate to be used as a probiotic

Monoassociation with Lactobacillus acidophilus UFV-H2b20 stimulates the immune defense mechanisms of germfree mice.

Probiotics are formulations containing live microorganisms or microbial stimulants that have some beneficial influence on the maintenance of a balanced intestinal microbiota and on the resistance to infections. The search for probiotics to be used in prevention or treatment of enteric infections, as an alternative to antibiotic therapy, has gained significant impulse in the last few years. Several studies have demonstrated the beneficial effects of lactic acid bacteria in controlling infection by intestinal pathogens and in boosting the host's nonspecific immune response. Here, we studied the use of Lactobacillus acidophilus UFV-H2b20, a lactic acid bacterium isolated from a human newborn from Viçosa, Minas Gerais, Brazil, as a probiotic. A suspension containing 10(8) cells of Lactobacillus acidophilus UFV-H2b20 was inoculated into groups of at least five conventional and germfree Swiss mice to determine its capacity to stimulate the host mononuclear phagocytic activity. We demonstrate that this strain can survive the stressing conditions of the intestinal tract in vivo. Moreover, the monoassociation of germfree mice with this strain for seven days improved the host's macrophage phagocytic capacity, as demonstrated by the clearance of a Gram-negative bacterium inoculated intravenously. Monoassociated mice showed an undetectable number of circulating E. coli, while 0.1% of the original inoculum was still present in germfree animals. Mice treated with viable or heat-killed Lactobacillus acidophilus UFV-H2b20 presented similarly improved clearance capacity when compared with germfree controls. In addition, monoassociated mice had twice the amount of Kupffer cells, which are responsible for the clearance of circulating bacteria, compared to germfree controls. These results suggest that the L. acidophilus strain used here stimulates a nonspecific immune response and is a strong candidate to be used as a probiotic.

[A dynamic study of the immune response of the population in a focus of hydatid disease in Dzhambul Province, Kazakhstan]. / Izuchenie dinamiki immunnogo otveta naseleniia v ochage gidatidoznogo ékhinokokkoza v Dzhambul'skoi oblasti Kazakhstana.

Screening for hydatid disease in foci should be carried out making use of the two most effective immunologic methods, indirect hemagglutination (IHA) and enzyme immunoassay (EIA). In order to have more reliable data on the structure of infection focus and for an earlier detection of patients such studies should be carried out over time and be followed by clinical examinations of subjects in whom anti-Echinococcus antibodies are repeatedly detected in epidemiologically significant and higher titers in IHA and/or EIA. All seropositive subjects and patients operated on for hydatid disease should be followed up.

[The dynamic activity of lymphocyte succinate dehydrogenase and its correlations in experimental malaria]. / Dinamika aktivnosti suktsinatdegidrogenazy limfotsitov i ee korreliatsionnykh sviazei pri éksperimental'noi maliarii.

Succinic dehydrogenase (SDH) activity in peripheral blood lymphocytes has been studied in progressing experimental malaria on a P. yoelii model, the strain 265 BY; the multinipple rats Mastomys natalensis. Cytochemical method employing n-nitrotetrazolium violet was used. Comparative analysis of changes in SDG activity in peripheral blood lymphocytes and changes in the level of parasitemia has demonstrated that day 10 was a critical period when there was an evident inverse correlation between the qualitative parameters. The findings give evidence of SDH participation in an adequate response of immunocompetent cells to malaria infection, thus leading to recovery.

[The outlook for the development of the immunodiagnostic and immunoprophylactic trends in parasitology]. / Perspektivy razvitiia immunodiagnosticheskogo i immunoprofilakticheskogo napravlenii v parazitologii.

The current state of immunodiagnostic and immunopreventive trends in parasitology and prospects for their development are analysed. The prospects of immunodiagnosis seem to be in increased sensitivity and specificity of tests by improving the methods and using the achievements of biotechnology in the manufacturing of high quality antigenic and antibody reagents. The development of immunoprevention of parasitoses can be stimulated by further studies of the mechanisms of a protective immune response, ways of its enhancement, search for natural and design of synthetic protective antigens and elaboration of new methods of their biological transport. The importance of the studies of local immunity phenomena is stressed for the development of new effective methods of immunodiagnosis and immunoprevention of socially valuable human parasitoses.

[Use of gnotobiotic animals for the study of the pathogenesis of cholera intoxication]. / Ispol'zovanie gnotobioticheskikh zhivotnykh dlia izucheniia patogeneza kholernoi intoksikatsii.

Germ-free suckling rabbits and minipigs can be recommended as models suitable for the study of different aspects of the pathogenesis of cholera intoxication. In minipigs, individual representatives of intestinal autochthonous microflora produce different effect on the sensitivity of the animals to the toxigenic and choleragenic action of Vibrio cholerae antigen introduced by oral administration, that should also be taken into consideration in the determination of residual toxicity during the trial of new vaccine preparations against cholera.

[Age and peripheral blood and phagocytosis indices in gnotobiotic and ordinary Wistar rats]. / Vozrastnye osobennosti pokazatelei perifericheskoi krovi i fagotsitoza u gnotobioticheskikh i obychnykh krys Vistar.

Age-related features of the peripheral blood (red cell and leukocyte counts, hemoglobin level) and phagocytic activity of peritoneal macrophages were studied in experiments on gnotobiotic and conventional Wistar male rats aged 2, 5, 9 and 35 months. With aging, the conventional Wistar rats showed a significantly lower phagocytic activity in the presence of a progressively increasing leukocyte count as compared with the gnotobiotic animals. The red cell count and hemoglobin level dropped in the conventional species with age, while the gnotobiotic ones manifested no appreciable changes in the indices reviewed.