Endometritis is one of the most frequently detected diseases of cattle, which is associated with disturbances in the microbial balance of the uterine cavity. This pathological process leads to disturbances in animal fertility, and, consequently, to economic losses in the dairy industry. In this regard, it is important to carry out timely preventive measures and have effective drugs for the treatment of postpartum endometritis. The aim of this study was to evaluate the effect of drugs based on bovine recombinant interferon "Biferon-B" and "EnrofloxacinferonB" on the taxonomic composition of bacteria in the uterine-vaginal discharge of patients with acute postpartum catarrhal endometritis of cows using high-throughput sequencing. It was found that the dominant species in the uterine cavity of cows with endometritis were Porphyromonas levii, Bacteroides heparinolyticus and Fusobacterium necrophorum. Bacterial taxa capable of causing various cattle diseases were detected in uterovaginal secretions. It was found that therapy of cows with the drug "Biferon-B" after 24 hours led to a tendency to increase the number of Caviibacter abscessus, Mycoplasmopsis californica and Histophilus somni. Statistically significant differences were found in the number of Porphyromonas SGB1983 before therapy (0.9%) and after therapy with "Enrofloxacinferon-B" during the first 24 hours (9.6%) (p<0.05). The study of the microbial diversity of utero-vaginal secretions of cows during therapy with "Enrofloxacinferon-B" on the seventh day established a tendency to decrease the relative abundance of bacteria Bacteroides heparinolyticus, Trueperella pyogenes and Mycoplasmopsis californica. The obtained data expand our understanding of the etiology of acute postpartum catarrhal endometritis in cows and the effect of drugs based on species-specific interferons on the course of this disease.

Impaired fertility in cattle is the cause of economic losses in livestock farms. Complex treatment of cows with acute endometritis may include various approaches, including the use of antibiotics and interferon-based drugs. The therapeutic approach associated with the use of immunostimulating substances is the safest. The aim of the study was to evaluate the blood parameters of cows during the treatment of acute postpartum catarrhal endometritis using «Enrofloxacinferon-B» and «GentabiferonB». It was found that therapy with «Enrofloxacinferon-B», «Gentabiferon-B», and the traditional treatment regimen led to an increase in phagocytic activity, which was probably due to the activation of the immune system of animals. At the same time, during therapy with «Enrofloxacinferon-B», a decrease in catalase activity was observed, which may be due to a decrease in the level of active oxygen forms in the blood of animals during therapy with this drug. It was also noted that during the therapy with «Enrofloxacinferon-B» no changes in the level of the circulating immune complexes were observed, while with the traditional treatment regimen an increase in this indicator was observed. Therapy with «Enrofloxacinferon-B» did not lead to an increase in neutrophils. At the same time, both the traditional treatment regimen and therapy with «Gentabiferon-B» led to an increase in the proportion of neutrophils. It is noteworthy that there was no pronounced negative effect on blood parameters of all three endometritis treatment options. It can be assumed that the most optimal treatment regimen for acute postpartum catarrhal endometritis in cows may be therapy including «Enrofloxacinferon-B» at a dose of 20 ml at intervals of 24 hours for 5 days.

The results of an experiment assessing the applicability of solutions of 6-oxo-2-phenylimidazo[1,2-b]pyrido[4,3-e][1,2,4]triazine-7(6H)-yl)acetic acid on plates and cellulose substrates for detecting excessive levels of volatile organic compounds associated with endometritis inflammation relative to biologically normal levels are considered. The fluorescent properties of the dye are studied using gynecological mucus from cows collected in various periods (pre- and post-partum) and nasal mucus from newborn calves. The test system responses were compared with clinically established diagnoses and the results of a microbiological study. An evaluation of the test systems revealed a false positive rate of no more than 11

The article presents materials on studying clinical and laboratory indicators of pregnant cows at 60 days of gestation, prone to the development of gestosis. In cows with the uterine fetal growth retardation syndrome at 2 months of pregnancy, subsequently complicated by gestosis, the established morphobiochemical changes indicate failures in the protein metabolism, functioning of the liver, kidneys, and the circulatory system. The changes also show an intensive accumulation of lipid peroxidation products, with a decrease in the activity of the enzymatic and non-enzymatic link of the AOD. The development of the fetal intrauterine growth retardation syndrome occurs against the background of a trophism disorders in the developing embryo. This at early stages of pregnancy is clinically manifested by a decrease in the size of the uterine horn cavity by 22.2-34.2%, the length of the fetus – by 41.5-48.9%, the body diameter – by 19.9-28.9%, the size of the corpus luteum of the ovary – by 15.7-24.1%.

The article presents the results of studying the efficacy of the drug based on granulocyte-macrophage colony-stimulating factor (GM-CSF) in cows with postpartum ovarian hypofunction. It has been established that its twofold administration at a dose of 10.0 ml/animal with a 7-day interval ensures the restoration of sexual cyclicity in 90.0% of cows with a reduction in the length of infertility by 18.0-30.1 days and the fertilization coefficient – by 0.56-0.78. A twofold use of the drug based on GM-CSF at a dose of 10.0 ml is accompanied by the development of dominant follicles, the diameter of which is by 46.6% larger compared to saline, an increase in the level of DHEA-S by 2.0 times, estradiol-17β – by 29.3%, which ensures a full manifestation of sexual cyclicity.

The level of expression of genes of proinflammatory (IL-1α and IL-1β) and antiinflammatory (IL-10) cytokines in the blood of cows was studied on 20 animals, divided according to the principle of analogues into two groups: the first group (n=10) - clinically healthy cows, the second one (n=10) - diagnosed with chronic endometritis. Diagnosis of chronic endometritis was carried out on the basis of the results of transrectal examination and echographic data obtained using a portable ultrasound scanner. The experiment included cows 60 or more days after calving. It has been found that the level of expression of IL-1α, IL-1β in cows with chronic endometritis is by 1.92 and 4.61 times higher, respectively, than in clinically healthy animals, and the anti-inflammatory cytokine IL-10, on the contrary, is by 118.6 times lower. The dominance of proinflammatory cytokine gene expression over anti-inflammatory ones indicates the development of an inflammatory process in the uterus, which is confirmed by the results of histological studies of endometrial biopsy material. In clinically healthy animals, the integumentary epithelium is lined with cells of a prismatic or cubic shape, the endometrium is slightly infiltrated with neutrophils, lymphocytes and histiocytes. The uterine glands are presented in a significant amount, the glandular cells are integral, prismatic in shape. In the cows with chronic endometritis, desquamation of the integumentary epithelium was diagnosed, the cells of which in most cases are in a state of dystrophy and necrobiosis. The lumen of the uterine glands is narrowed, glandular cells are rejected into the lumen of the glands, which indicates a decrease in the functional activity of the organ. The endometrium looked edematous, abundantly infiltrated, predominantly with neutrophilic leukocytes and, to a lesser extent, with lymphoid cells, indicating the presence of inflammation in the uterine mucosa.

The article presents the material of study on clinical and echographic parameters of pregnant cows with various gestation pattern. The syndrome of fetal developmental retardation is recorded on average in 33.3% of pregnant animals, including complicated by gestosis – in 22.6%. In the cows with fetal developmental retardation syndrome at 135-150 days of gestation, a decrease in the intensity of blood supply to the developing embryo was observed, manifested by a decrease in the size of the placenta by 33.8-46.7% and the diameter of the middle uterine arteries – by 14.7-24.5%. Fetal developmental retardation syndrome complicated by gestosis at 7 months of gestation is clinically characterized by hypertension, edema in 85.8% of animals and the presence of protein (1.0 mg/ml or higher) in the urine.

Indicators of the blood coagulation system (thrombin time, prothrombin time, activated partial thromboplastin time - aPTT) were studied on 42 pregnant cows at 60-75, 135-150 and 210-230 days of pregnancy, divided according to the principle of analogues into three groups: physiological course, fetal growth restriction syndrome without late toxicosis of pregnancy, fetal growth restriction syndrome complicated by gestosis. Pregnancy was diagnosed using transrectal and ultrasound examinations. Fetal growth restriction syndrome was diagnosed at 60-75 days of pregnancy using an ultrasound scanner with a linear sensor with a frequency of 7.5 MHz. Late toxicosis of pregnant animals was diagnosed at 210-230 days of pregnancy by the presence of hypertension, proteinuria and edema. Blood samples were taken from the animals included in the experiment to determine the platelet content, thrombin and prothrombin time and aPTT. It has been established that platelet content is an informative indicator for predicting gestosis in the first five months of pregnancy with a sensitivity of 80.0% and specificity of 87.5%. The sensitivity of thrombin time at 60-150 days of pregnancy is 77.8%, specificity - 90.0%, prothrombin time - 70.0 and 88.9%, aPTT at 135-150 days of pregnancy - 77.8 and 85.7%, respectively. Prognostic markers for early diagnosis of late toxicosis in pregnant animals, determined at 2 months of pregnancy are: platelet level - 451.2 x 109/L and higher; thrombin time – 87.3 seconds and below; prothrombin time – 35.1 seconds and below. Indicators for early diagnosis of gestosis, determined at 5 months of pregnancy, are: platelet level - 437.5 x 109/L and higher; thrombin time – 78.6 seconds and below; prothrombin time – 30.3 seconds and below; aPTT – 41.8 sec and below.

The article presents the material for studying the expression level of pro- and anti-inflammatory cytokine genes in the blood of cows with ovarian hypofunction and the use of the drug based on gm-csf (granulocyte-macrophage colony-stimulating factor). It has been established that disorders in the functional activity of the genital gonads in cows occur against the background of an increase in the relative expression level of genes of pro-inflammatory cytokines (IL-1β - by 1.56 and 2.11 times, IL-2 - by 1.41 and 2.29 times, TNFα - by 19.5 and 48.8%), while reducing anti-inflammatory ones (IL-4 - by 27.6 and 37.9%, IL-10 - by 8.3 and 36.1%). An imbalance between the expression level of pro- and anti-inflammatory cytokines in the blood of cows is one of the etiological factors leading to hormonal imbalance and the development of hypofunctional ovarian disorders. The administration of a drug based on gm-csf to cows during insemination once at a dose of 5.0 ml to normalize the functional activity of the ovaries in case of their hypofunctional state with anovulation phenomena contributed to a decrease in the expression level of IL-1β by 27.3%, IL-2 – by 16.7%, TNFα – by 8.2%, with an increase in the expression of IL-4 by 4.8%, IL-10 – by 6.1%, which ensured a clinical efficacy of 86.7%. The use of a drug based on gm-csf in the cows with ovarian hypofunction, manifested by anaphrodisia, twice with an interval of 7 days at a dose of 10.0 ml provided a decrease in the expression level of IL-1β - by 1.9 times, IL-2 – by 38.5%, TNFα – by 14.8%, with an increase in IL-4 - by 11.1%, IL-10 – by 39.1% and a clinical efficacy of 90.0%.

The state of the immunobiochemical status of the blood of cows when using a drug containing gm-csf was studied on 15 animals with a hypofunctional state of the ovaries. The animals were divided according to the principle of analogues into three groups. The animals were included in the experiment 45- 60 days after calving without signs of sexual cyclicity. The cows of the first group were injected with a drug based on gm-csf (granulocyte-macrophage colony-stimulating factor), the cows of the second one - follimag, the third group served as a negative control without the introduction of drugs. Evaluation of the efficacy of the use of gonadotropic and recombinant drugs showed that the use of the agent based on gm-csf turned out to be the most effective in comparison with follimag and the negative control. After the use of the drug of recombinant interferons, the content of circulating immune complexes turned out to be lower by 30.9%, malon dialdehyde - by 17.1%, medium molecular peptides - by 34.9% TNFα - by 21.0%, IL-1β - by 41.1%, IL-2 - by 35.9%, with an increase in serum bactericidal and lysozyme activity by 13.8% and 21.7%, respectively, phagocytic index - by 12.9%, phagocytic number - by 18.4%, progesterone - by 5.09 times, estradiol - by 29.3%, dehydroepiandrosterone sulfate - by 78.9%, IL-4 - by 44.6%, IL-10 - by 20.3%, which indicates activation the humoral link of general nonspecific resistance, an increase in the content of anti-inflammatory cytokines, with a decrease in the intensity of lipid peroxidation processes, the level of proinflammatory cytokines against the background of the restoration of the hormoneproducing function of the sex gonads. Changes in the indicators of the immunobiochemical blood status of cows are reflected in the activation of the functional activity of the ovaries, the manifestation of full-fledged sexual cycles by animals and successful insemination.

The article presents the material on the study of clinical and morphological indicators of endometrial glandular-cystic hyperplasia in cows. It has been established that the share of endometrial hyperplasia glandulocystica in cows accounts for 11.4% of the total number of chronic uterine diseases. Most often, this pathology is diagnosed in cows 120 or more days after calving with an annual milk production of 6000-7000 kg. Glandular-cystic hyperplasia of the endometrium is most typical of the animals of the Red-Motley and Simmental breeds with loose keeping. Endometrial hyperplasia glandulocystica is characterized by a thickening of the uterine wall up to 6.5±0.28 mm, the presence of a cavity in the uterine horns of 3.4±0.19 mm, follicular cysts in the ovaries with a diameter of 42.5±2.8 mm. Endometrial hyperplasia glandulocystica is characterized by an increase in the height of the cells of the covering epithelium up to the height of prismatic one, growth of the uterine glands with the expansion of their lumens, an increase in height and vacuolization of the glandular epithelium. In case of glandular-cystic hyperplasia, uterine glands account for 28.6%, blood vessels – 12.3%, covering epithelium – 5.7%, which is by 1.88-1.97 times more, compared to clinically healthy animals. The height of the cells of the covering epithelium in case of this pathology is higher by 13.1%, the height of the epithelial cells of the uterine glands – by 23.4%, the thickness of the endometrium – by 1.38 times, which indicates endometrial hypertrophy.

The article presents the data on the frequency of isolation of postpartum metritis pathogens in dairy cows. The microflora of cervical-vaginal mucus and exudate (n=150) was isolated in the form of monocultures in 44.7% of cases, in the form of associations - in 55.3% of cases. E. coli was most often isolated, which allows us to consider it one of the main causative agents of this disease. At enterprises with loose keeping, the microbial landscape of the genital tract of cows with postpartum metritis had a wider range of pathogens, which was represented by numerous associations. Fusobacterium necrophorum and Actinomyces pyogenes were also isolated from these animals, contributing to a more severe course of the inflammatory process with its manifestation.

A comparative assessment of the indicators of immunological resistance and the level of proinflammatory cytokines in cows with physiological and complicated postpartum period was carried out. It has been shown that in the animals with postpartum metritis, against the background of a decrease in immunological resistance, the production of proinflammatory cytokines 6-8 days after calving increases, INF-γ – by 23.0%, IL-2 – by 3.4 times (P<0.001), TNFα – by 2.7 times (P<0.001), which indicates the inflammatory process development, and in those who remained healthy, INF-γ decreases by 3.0%, IL-2 – by 1.4 times (P<0.01 ), TNFα – by 1.5 times (P<0.01), which indicates the physiological course of the postpartum period.

The article features the results of the morphological, biochemical and immunological studies of cow’s blood in the treatment of acute postpartum endometritis using antimetrimast. Complex treatment of cows with acute postpartum en-dometritis provides for the intrauterine administration of antimicrobial agents and intramuscular injections of the drug antimetrimast administered on three occasions with a 24-hour interval, starting from the first day of the therapeutic course, at a dose of 10 ml. The treatment is accompanied by the clinical recovery in 90.9% of animals, decrease in abnormalities of inflammatory nature, processes of lipid peroxidation, activation of the humoral and cellular component of immunity, enzymatic and non-enzymatic components of antioxidant protection.

The article presents the material on studying the efficacy of the use of a new complex antimicrobial drug for the treatment of cows with chronic endometritis, which contains antibiotics from the group of penicillins and aminoglycosides. Clinical studies were conducted to determine the optimal dose, interval of administration of an antimicrobial drug as part of the complex treatment of chronic endometritis. Treatment of cows with chronic endometritis was complex, involving the use of general stimulants (placenta denatured emulsified subcutaneously at a dose of 25.0 ml/animal on days 1, 5 and 9 of treatment) and symptomatic agents (magestrofan intramuscularly at a dose of 2 ml/animal on the first day of treatment and uteroton four times at a dose of 10.0 ml/animal, starting from the second day of therapy). It has been established that the optimal scheme for the use of an antimicrobial drug in the treatment of chronic endometritis is intrauterine administration at a dose of 20.0 ml/cow with a 24-hour interval that helps to reduce the number of intrauterine injections. This dose schedule for an antimicrobial drug in combination with general stimulants and symptomatic agents promotes the clinical recovery of 82.3%, which is by 9.0% higher, compared to metricure. After a clinical recovery of the animals that were intrauterinely injected with a new antimicrobial drug, 85.7% were fertilized, the period from the treatment onset to fertilization was 50.6±3.4 days, and the fertilization rate was 2.12.

The article presents the results of the efficacy of using the drug antimetrimast for the prevention of postpartum endometritis in cows. Administration of antimetrimast on three occasions, starting on the first day after calving, with a 24-hour interval at a dose of 10 ml/animal, provides a 3.3-fold decrease in the incidence of postpartum endometritis in cows, a 2.0-fold increase in prophylactic efficacy, and an increase by 42.7% in the number of fertilized animals. The application of antimetrimast for prophylactic purposes helps reduce the inflammatory reaction in the uterus and activate the humoral and cellular elements of the general nonspecific resistance of bovine organism.

The article presents the material on studying the morphobiochemical blood status of cows in the complex therapy of chronic endometritis. It has been established that the use of general stimulant (biostimulgin subcutaneously with a 48-hour interval at a dose of 25.0 ml/animal), symptomatic (uteroton three times with a 24-hour interval at a dose of 10.0 ml/animal) drugs and a new antimicrobial drug (intrauterine 1-2 times with a 24-hour interval at a dose of 20.0 ml/animal) is accompanied by the normalization of inflammatory processes in the reproductive organs, lipid metabolism, liver function, activation of the cellular and humoral link of nonspecific resistance of the organism, the antioxidant system, a decrease in the intensity of lipid peroxidation processes, predominance of anti-inflammatory processes over pro-inflammatory ones.

The article presents the material on studying the blood content of interferon-tau, progesterone and cortisol in cows when using the drug tautin. The use of tautin twice at a dose of 10.0 ml provides an increase in the level of interferon-tau by 8.2 times on days 15-17 after insemination, compared with the initial value, which is by 23.8-38.6% higher than after its single application and by 70.7% - than in intact animals. The pregnancy after a double administration of tautin proceeds against the background of an increased content of progesterone and cortisol, the level of which is higher by 36.9-62.7% and 41.1-52.5%, respectively, which contributes to the preservation of gestation and provides optimal conditions for the nutrition of the developing embryo.

The article presents the material on studying the efficacy of the new drug proovulin for the treatment of cows with follicular cysts. It was established that the double administration of proovulin, containing granulocyte-macrophage colony-stimulating factor (GM-CSF), at a dose of 10.0 ml with an interval of 4 days, is accompanied by an efficacy of 83.3% that is by 3.3-8.3% higher, compared to the dose of proovulin of 5.0 ml and surfagon, while reducing the period from calving to fertilization by 18.9-35.7 days and the fertilization rate - by 0.29-0.45. The restoration of the functional activity of the genital gonads in cows with follicular cysts when using proovulin occurs against the background of the normalization of their hormonal-cytokine profile that is manifested by an increase in progesterone production by 10.0 times, which leads to a decrease in the level of TNFα by 20.1%, as well as the concentration of IL-1β - by 18.9%.

The article presents the material on studying the efficacy of the preparation of recombinant interferons containing granulocyte-macrophage colony-stimulating factor (GM-CSF) for the prevention of the post-estral uterine bleeding in dairy cows, accompanied by a retardation in ovulation of the dominant follicle. It has been found that a single administration of the drug containing GM-CSF in its composition to cows at a dose of 5.0 ml during insemination, contributes to the ovulatory functional recovery in 86.7% of animals, and reduces the period from calving to fertilization by 27.7 – 37.8 days. The introduction of the recombinant interferon preparation to cows provides activation of the cellular link in the immune defense, normalization of the blood hormonal-cytokine profile, recovery of the ovulatory function in the genital gonads. This is manifested by an increase in the serum lysozyme activity – by 29.5%, leukocyte phagocytic activity – by 12.4%, phagocytic index – by 38.8%, phagocytic number – by 58.8%, progesterone – by 59.9%, estradiol – by 60.0%, testosterone – by 59.3%, DHEA-S – by 56.8%, IL-4 – by 42.5%, IL-10 – by 53.4%, with a decrease in the content of IL-2 – by 40.4% and IL-1β – by 37.2%.