IMBALANCED IMMUNOBIOLOGICAL REACTIVITY, INFECTION AND MUTAGENESIS FACTORS IN THE HEPATOBILIARY SYSTEM AFFECTED BY A NATURAL FOCAL HABITAT FACTOR – A TREMATODE INVASION BY OPISTHORCHIS FELINEUS

An interaction between decreasing host anti-infective defense due to long-term invasion with Opisthorchis felineus in the hepatobiliary system, duct bile colonization by microflora and revealing the endogenous mutagenesis (carcinogenesis) factor - secondary bile acids - in bile is considered in the article. The role of organism genotype in the pathogen-related immune response to Opisthorchis felineus trematode and helminth development in the hepatobiliary system has been shown. The role of dysregulated mechanisms of tissue homeostasis in induction of compensatory chronic homeostatic proliferation and somatic cell oncogenesis is discussed. The study results evidence that disturbed functioning of the regulatory T-cells, inhibition of the NK cell effector function and very high functional activity of the memory B-cells are of great importance in imbalanced host immunobiological reactivity, caused by chronic opistorchosis invasion. Decreased host anti-infective protection causes intrahepatic bile duct infection with different bacterial species. Presence of secondary bile acids in hepatobiliary system was associated with biliary bacterial strains inhabiting intestinal tract: Proteus vulgaris*, Proteus mirabilis*, Citrobacter freundii*, Bacteroides alcaligues faecalis*, Clostridium*, Streptococcus faecalis*, Еscherichia coli* (*gut microflora). Participation of microbiota in bile acid biotransformation immediately in the duct bile has been confirmed in in vitro experiments. Experimental methods on Drosophila melanogaster and Salmonella tiphimurium strains: TA 100, TA 98 allowed to find out that bile from chronic opistorchosis patients exerts higher mutagenic activity compared with control groups. Mutational events in somatic and bacterial cells depend on the presence of secondary bile acids (deoxycholic, lithocholic) in duct bile, as well as the level of total bile acid concentration. The study data confirm the concept by Professor A.A. Shain about presence of endogenous risk factor for developing primary cholangiocellular liver cancer such as secondary bile acids in the bile of chronic opistorchosis patients. A concept of cholangiocarcinogenesis, based on mutational events, is added up with disturbance of generative cycle in tissue cells and their differentiation due to decreased kylon factor activity, as well as sensitivity threshold to it. Level of investigation and understanding of mechanisms underlying cholangiocarcinogenesis during chronic opisthorchiasis invasion will allow to develop pathogenetic approaches to correct homeostasis regulation and prevention of cholangiocarcinomas.

Influence of the prebiotic Bio-active on natural resistance, safety and productivity of young pigs

The primary task of the livestock industry is to provide the population with high-quality food products, and the industry with raw materials. For this, it is necessary to ensure a high level of productivity and safety of young pigs. Studies carried out in recent years indicate an increase in the incidence of gastrointestinal diseases among young farm animals, leading to a decrease in the immunobiological reactivity of the piglets' organism and significant damage to farms. When performing the research, we used zootechnical, zoohygienic, biochemical, immunological and variational-statistical research methods. Research work was carried out during 2010-2018 at the Department of Animal Hygiene and Fundamentals of Veterinary Medicine of the Bila Tserkva National Agrarian University. Scientific and economic experiments and production tests were carried out in the farms of Progress LLC (Uzin, Bila Tserkva district) and Denisenko LLC (Skvirsky district, Kyiv region). Experimental studies were carried out in the Problem Laboratory of Immunology, Department of Animal Hygiene and Fundamentals of Veterinary Medicine, interfaculty laboratory of biochemical and histochemical research methods. For the first time, the prebiotic Bio-active was used as a feed additive in the diet of young pigs on growing at industrial keeping, its positive effect on the safety, productivity, physiological and immunological state of their body was proved. For the first time, the optimal dose of the prebiotic Bio-active for growing pigs was established and a method of its use was developed. The optimal dose of the prebiotic Bio-active for growing young pigs is 5 g (5x107 CFU) per 10 kg of body weight when fed with compound feed once a day for 30 days, which contributes to an increase in the average daily weight gain of piglets by 17.2 % (P <0.01) and 16.6 % (P <0.05) on the 30th and 60th days of the study, respectively. Feeding pigs with Bio-active promotes an increase in the content of total blood serum protein by 7.2 % (P <0.05), albumin – by 5.2 %, γ-globulins – by 6.3 %, an increase in AST activity – by 23, 1 % (P <0.05) and ALT – by 22.4 % (P <0.01). In the peripheral blood of rearing pigs under the influence of the prebiotic Bio-active, the proliferation, differentiation and specialization of immunocompetent cells increase: an increase in the total number of T-lymphocytes by 5.43 % (P <0.05), B-lymphocytes by 2.85 %, a decrease in the content of 0-lymphocytes – by 8.29 % (P <0.05). The number of medium-avid T-lymphocytes also increases – by 9.19 % (P <0.05) and B-lymphocytes – by 10.28 % (P <0.05) due to a decrease in the level of low-avid immunocompetent cells. The use of the prebiotic Bio-active in an optimal dose promotes the activation of metabolic processes, antigen-nonspecific immunity and an increase in the body weight of pigs. Key words: industrial pig breeding, rearing young pigs, housing conditions, gastrointestinal canal, prebiotic, immunobiological reactivity, metabolism, safety.

Ways to increase the immunogenicity of inactivated vaccines against strangles

The results of the study on the specific prevention of infectious diseases in horses are presented. Methods have been developed to increase the immunogenicity of environmentally friendly vaccines against strangles, caused by the beta-hemolytic streptococcus – Sreptococcus equi. The work was carried out in laboratory conditions and horse breeding farms of the Republic of Sakha (Yakutia). The toxicity and immunogenicity of the vaccine was determined by conventional methods on young horses. Based on the study of the immunobiological reactivity of young horses, the use of immunomodulators in the development of inactivated vaccine preparations has been substantiated. Vaccines with immunomodulators were tested and registered in accordance with approved research methods for medicinal products for veterinary use. Polyribonate (polyvedrim) and culture liquid (fugate) from the bacterial strain Bacillus subtilis TNP-3 were used in the composition of vaccines as an immunomodulator. To prepare a vaccine against strangles, strains of bacteria Streptococcus equi H-34 and Streptococcus equi "H-5/1" were used, which were deposited in the Russian State Collection of Microorganism Strains of the Russian State Center for Animal Feed and Drug Standardization and Quality. After immunization with inactivated vaccines containing immunomodulators, the effectiveness of vaccines increases by 20% and reaches 90%. Vaccines increase the body's immunobiological reactivity. The most effective were the “Tabyn” vaccine and the vaccine from the Streptococcus equi strain H-5/1 with fugate, the Bacillus subtilis strain TNP-3. The polyribonate vaccine was approved in Russia (2000), the “Tabyn” vaccine is used in Kazakhstan (2018). These vaccine preparations, which ensure high antiepizootic efficacy, are environmentally friendly, since they do not contain toxic substances and antibiotics.

Peculiarities of sheep pathogenesis at associative invasions of gastrointestinal tract

In the Republic of Belarus, primarily in farms with imperfect technology, parasitic diseases of sheep are widespread, including: nematodes of gastrointestinal tract, strongyloidosis, eimeriosis, monieziosis, trichocephalosis, cryptosporidiosis, etc. Study of impact of associative parasitosis of sheep on the immunobiological reactivity of animal body has recently become more and more theoretical and practical for rational use of drugs in treatment of these diseases. The purpose of research is to study peculiarities of sheep pathogenesis at associative invasions of gastrointestinal tract. The study was carried out at farm “Villia-agro”, Kobrin district, Brest region. Lambs of 2-4 months of age spontaneously infested with parasites of gastrointestinal tract have been selected. Parameters of cellular immunity were determined: number of leukocytes, monocytes, neutrophils, eosinophils, level of rosette-forming T- and B-lymphocytes and humoral immunity: circulating immune complexes, total protein, protein fractions, including proteins of C3 complement system and immunoglobulins, macro and microelements (calcium, phosphorus and iron) in blood serum. With spontaneous invasion of sheep by associations of parasites of gastrointestinal tract, the following changes have been determined: significant decrease in number of lymphocytes, T-lymphocytes, concentration of total protein, albumin, - β- and g-globulins, calcium and phosphorus. Significant increase in leukocytes: Eosinophils and stab neutrophils, a1-globulins , circulating immune complexes. All this together indicates disturbance in functioning of body’s immunity and requires immediate appropriate treatment aimed both at destroying associations of parasites of gastrointestinal tract and restoring immune system of animal’s body. These studies will form basis for development of rational system for therapeutic and preventive measures for associative parasitosis of sheep in the Republic of Belarus, which will reduce economic damage from these diseases and improve quality of livestock products.

Role of intestinal microbiota in development of atopic dermatitis and methods of its treatment in case of its violation

Representatives of the normal microflora of intestinal biota perform a physiologically important function of maintaining the constancy of the internal environment of the body, take part in the formation of the immunobiological reactivity of the macroorganism. Violation of normocenosis contributes to the chronicity of pathological processes (in particular, atopic dermatitis).Material and methods. Under supervision were 36 patients with atopic dermatitis. Before treatment, 86.1 % of patients had persistent or intermittent clinical symptoms of dysbiosis. Depending on the treatment, patients were divided into 2 groups: group 1 (n = 19) received an external preparation with zinc pyrithione (Cinokap® cream / spray depending on the prevailing clinical picture), specialized dermatocosmetics. In addition to topical therapy, patients of group 2 (n = 17) received Lactofiltrum® 2 tablets 3 times a day for 14 days.Results. After 4 weeks, the total index of the DIHS index decreased in the 1st group by 78.8 %, in the 2nd group by 85.8 %, BRS decreased in the 1st group by 89.2 %, in the 2nd group by 97.1 %. By the end of the course of therapy, DIC improved by 62.4 and 84.1 %, respectively.Conclusions. The inclusion of the drug Lactofiltrum® in the treatment complex leads to a more rapid and pronounced regression of skin rashes and subjective sensations, normalization of the gastrointestinal tract, which contributes to a significant improvement in the quality of life. The drug has a favorable safety profile, convenient to use.

Immunobiological status of the body of cows during mastitis

The work reveals the immunobiological aspects of lactation of cows and changes in immunobiological reactivity in the development of mastitis.The authors present modern scientific data on the local immune protection of the mammary gland of cows. Main stages of ontogenetic development of cellular immunity of the mammary gland of cows were traced during clinical and experimental studies. The number of somatic cells in the secret of the mammary gland of the primates was dependent on the period of the functioning of the mammary gland. In the cytology of colostrum mostly (56.00 ± 1.90%) neutrophil granulocytes were predominant, in the middle period of lactation (3–5th month) the proportion of epithelial cells increased (from 29.51 ± 2.17 to 49.59 ± 1.94%), during the launch period, the population of polymorphonuclear neutrophil granulocytes was changing as well, which virtually recovered to the original level and increased during the dry period. However, at the end of lactation, during the onset and dry, with the development of involutionary processes in the mammary gland, a sharp decrease in cytochemical reactivity of intracellular lysozyme of phagocytic cells was observed. To conduct clinical and experimental studies, three groups of animals were formed. As a result, it was found out that subclinical mastitis of cows is accompanied by a change in the immunobiological reactivity. Purulent-catarrhal mastitis in cows was manifested by significant changes in the parameters of nonspecific immunological reactivity. In the peripheral blood of cows with subclinical mastitis, the number of reactive microphages increased sharply (P < 0.001). In parallel with this, the number of activated phagocytes with myeloperoxidase granules also increased in the peripheral blood (P < 0.01). Activation of intra-leukocyte lysozyme phagocytic cells was less intensive. Subclinical udder pathology was accompanied by an increase in the number of degranulated cells (P < 0.001), which is one of the specific properties of cytomorphological changes in programmed death (apoptosis). Subclinical inflammation of the mammary glands mastitis of cows was accompanied by a certain decrease in the number of T-lymphocytes (P < 0.001). Clinical and experimental studies have shown that subclinical and purulent-catarrhal mastitis of cows undergo significant changes in systemic immunity. In the pathophysiological model of subclinical and purulent-catarrhal mastitis, the functional state of the T-link of specific immunity was disturbed, the bactericidal activity of blood serum and phagocytosis were suppressed, which occurred against the background of changes in the cytochemical reactivity of phagocytic cells circulating immune complexes and molecules with an average molecular weigh.

Dental diseases in cats

The article deals the results of searches on the prevalence, etiological factors and pathogenic mechanisms of certain dental diseases in cats. The analysis of literary data of domestic and foreign scientists testifies, that among dental diseases in cats the largest group consists of periodontal diseases. The changed type of feeding, the imbalance of the ration, the lack of complete self-cleaning of the teeth lead to a decrease in the immunobiological reactivity of the organism. Incorrect bite, deformation of the teeth, parodontopathy, etc. cause an animal's discomfort, cause complications in the cardiovascular, respiratory and other systems. Periodontopathies are registered, for the most part, in adult cats. The etiological factors of periodontal diseases are local and general. The starting mechanism of the inflammatory process in the peritoneal tissues is a violation of the ratio of various associations of microorganisms, the balance of which depends on the presence of dental plaque and dental stone. The results of research of many scientists testify that periodontal diseases are accompanied by complicated and profound disorders at the morphological level, as well as systemic changes in metabolic, biochemical, immunological and endocrine reactions. In the absence of prevention, untimely diagnosis of periodontal disease and the treatment of dental sick cats irreversible changes in the dental system of animals are developed. Diseases of the oral cavity in cats is one of the main causes of loss of teeth, the emergence of deformations, the formation of chronic foci beyond the oral cavity and the development of various forms of somatic pathology. Therefore, to prevent the development of periodontal disease and their complications in cats it is necessary to develop effective measures for the prevention of diseases of the parolont, and for stomatologically sick animals - methods of treatment with the use of new medicinal substances.