COMPREHENSIVE METHODS OF DIAGNOSIS AND PREVENTION OF POSTPARTUM COMPLICATIONS IN COWS

The experiments were conducted during 2018 - 2020 on cows of black-spotted breed in the conditions of LLC "Ryasnyanske" of Krasnopil district of Sumy region. 
Cows were aged 4 - 8 years with an average annual milk yield of 2.5 - 3.1 thousand kg of milk per lactation. Assessment of the postpartum period was performed according to the changes that occurred in the female reproductive system. This took into account not only the general condition of the animals, the nature of the exudate, the size and topography of the uterus, but also the condition of the ovaries, cervix and vagina in rectal and vaginal examinations. Diagnosis of various forms of endometritis was performed based on medical history, clinical and gynecological studies. 
For the treatment of cows of the experimental group with postpartum endometritis, they were injected subcutaneously with 10 ml of the drug "Metrisan" in a mixture with 0.5% solution of novocaine at a rate of 1: 1. The interval between injections was 7-10 days. The frequency depended on the form of endometritis and was 3-5 injections. For the treatment of cows of the control group with postpartum endometritis they used a 10% solution of ichthyol intrauterinely Injection of 7% solution of ichthyol into pararectal tissue 
In 2018, 2 cows (1.6%) dropped out for this reason, in 2019 - 4 heads (3.1%), in 2020 -4 cows (2.8%). Due to age-related infertility, 1 cow was culled in 2018 (0.8%), 2 cows were culled in 2019 (1.3%), and 2 heads were culled in 2020 (1.4%). Due to injuries in 2018, 1 cow was discarded (0.8%), in 2019 1 cow was culled (0.8%), in 2020 1 cow was culled (0.7%). In 2018, the most common pathology of the postpartum period was vulvo vaginitis 8%, endometritis - 6.5%, artificially acquired infertility - 0.8%. In 2019, 9.8% of cows had endometritis; vaginitis, vulvitis, cervicitis - 8.3%, artificially acquired infertility was 0.8%. In 2020, endometritis was 17%, vaginitis, vulvitis, cervicitis - 9.2%, artificially acquired infertility was 0.8. According to the results of the research, the therapeutic efficacy was higher in the experimental group, where the therapy of cows with acute purulent-catarrhal endometritis using the drug sepranol and amoxicillin-150 was used. 
The total number of days of infertility in the control group was 125 days, in the experimental - 60 days. In terms of 1 head it is: in the control group - 25 days, in the experimental -12 days. The duration of the period from birth to fertilization in the control group is 55 days, in the experimental group - 42 days.

Prevention of postpartum diseases in uterine cattle and reducing the incidence and death of newborn calves is one of the main problems of veterinary science and practice in the field of non-infectious pathology (Gilbert R. O., 2016).
One of the urgent problems that need to be solved in veterinary obstetrics is the prevention and treatment of such postpartum diseases in cows as sub involution of the uterus, endometritis, cervical and ovarian diseases (Pascal, N., Olivier Basole, K., Claired' Andre, H., & Bockline Omedo, B., 2021).
The practice of veterinary medicine in recent years has registered a trend towards the spread of obstetric and gynecological diseases in domestic animals (Potter et al., 2010). For the treatment of females with obstetric and gynecological pathology, more than 50 thousand different compounds are used, of which more than eight thousand are antibacterial in nature (Roman Rudakov, Liliya Khamitova, Anastasiya Metlyakova & Vyacheslav Milaev, 2020).
Rational complex therapy requires the use of drugs that act on different parts of the pathological process, the basis of which is intrauterine administration rational complex therapy requires the use of drugs that act on various parts of the pathological process, the basis of which is the intrauterine administration of broad-spectrum antibacterial drugs. The use of

Literature Review
Postpartum endometritis (acute endometritis) inflammation of the uterine mucosa with an acute course, which is accompanied by significant changes in the endometrium and increased activity of healthy or regenerated uterine glands, according to the pathological process and the nature of the secretion of mucus is diagnosed: -Endometritis catarrhalis characterized by the release of catarrhal exudate; -Endometritis Catarrhalis et Purulenta, in which the discharge from the genitals are mucous -purulent nature -Endometritis purulenta -secretion of purulent exudate (Le Blanc S. J., 2014); According to some authors, the leading role in the pathogenesis of endometritis belongs to the development of autonomic neuroses in the uterus (Dahl-Pedersen, K., Herskin, M. S., Houe, H., & Thomsen, P. T., 2018). It is established that regardless of the etiology of the inflammatory process (aseptic or infectious), it is accompanied by constant irritation of the nerve endings of sympathetic nerves, which eventually leads to the development of degenerative processes with subsequent accumulation in tissues of deoxidized products and increased activity of hyaluronidase (Gilbert R. O., 2016). At the same time in the places of inflammation there is a violation of blood circulation, this is, the physiological distribution of blood flowing in the tissue of the organ is inhibited due to the so-called microcirculation through arterioles-capillaries-venules (Al-Bagdadi, F., Eilts, B., & Richardson, G., 2004). The mechanism of impaired blood microcirculation in the area of inflammation depends on the nature of the primary pathogen and can occur due to vasospasm, thrombosis, as well as -as a consequence of paresis of the venules, the subsequent development of venous stasis. In all cases, regardless of the mechanism of microcirculation, simultaneously with the spasm of small vessels comes the expansion of arterio-venous anastomoses, through which arterial blood, passing the capillary network, enters the venous system. Thus, hypoxia always develops in the area of the inflammatory process, which further complicates the course of the inflammatory reaction (Mohammed, Z. A., Mann, G. E., & Robinson, R. S., 2019).
Inflammatory processes are usually associated with the penetration of infection, although endometritis is always an infectious process (but not contagious, non-infectious) ( Some authors see a significant role in the pathogenesis of postpartum infection of immune disorders, which leads to a decrease in anti-infective resistance of the organism, even to opportunistic pathogens and auto flora (Mohammed, Z. A., Mann, G. E., & Robinson, R. S. 2019).
In the acute course of the disease, the general condition does not differ significantly from the norm, but for several days periodically or constantly from the genitals secreted mucopurulent exudate. There is a development of persistent changes in the mucous membrane, muscular and serous layers of the uterus, and these changes are often irreversible

Diagnosis.
The transition from acute to chronic inflammation is very difficult to diagnose in time by clinical signs and even by immunological analysis. The effectiveness of the diagnosis of chronic inflammation is insufficient, because it is carried out without taking into account the pathogenesis of the disease (Dubuc, J., Duffield, T. F., Leslie, K. E., Walton, J. S., & LeBlanc, S. J., 2010). The diagnosis is made comprehensively on the basis of anamnestic data, clinical and obstetric examination of the animal and laboratory tests. At clearly expressed clinical signs of endometritis diagnosis is not difficult. In the absence of clinical signs, an endometrial biopsy is performed, followed by histological examination of samples (Mohammed, Z. A., Mann, G. E., & Robinson, R. S., 2019). Many different methods have been proposed for the diagnosis of latent endometritis and various data on their effectiveness have been obtained.
In practice, the diagnosis is made visually, that is evaluate the mucus taken from the cow during heat for the presence of small flakes of manure, discoloration, but this condition is not found in all sick animals. Laboratory methods allow the most objective judgment of pathological changes that occur in the female reproductive system, but they are expensive, time-conTotaling and economically unprofitable for practical use (Brewer, The bacteriological method is not always reliable, because the uterine cavity may be free of microbes. The most accurate and easily accessible method is a bioassay. The condition of the endometrium can be judged by examination of the smear -imprint on the cytological picture (Al-Bagdadi, F., Eilts, B., & Richardson, G., 2004).
In subclinical endometritis, histamine can be detected in the urine of patients using a slap test ( A fairly accurate method of diagnosing subclinical endometritis is the Fol's method, which allows you to detect sulfur-containing amino acids in the leaky mucus (Barański, W., Podhalicz-Dzięgielewska, M., Zduńczyk, S., &Janowski, T., 2012). To achieve these goals, non-specific, pathogenetic and symptomatic therapies are recommended, aimed at both the pathogenic focus and the normalization of body function as a whole.

Treatment
It is well known that the use of even the most effective therapeutic agents against the background of low resistance does not give a positive result. Therefore, to increase the body's resistance to cows in gynecological diseases, modern clinicians recommend various methods among which the leading place belongs to the works on tissue therapy ( For the treatment of cows with chronic endometritis, offer drugs that have long-term antimicrobial action (Elsayed, Doaa H., El-Azzazi, Fakhri E., Mahmoud, Yasmina K., Dessouki, Sherif M., &Ahmed, Eman A., 2020). Using antibacterial drugs, we warn of generalization (spread to surrounding tissues) of inflammation, which is currently the prevention of sepsis (Le Blanc S. J., 2014). Drugs injected into the uterine cavity should be indifferent to the internal environment of the uterus, replacing it with properties. It is especially important that they do not destroy or shrink the mucin of the uterus (Al-Bagdadi, F., Eilts, B., & Richardson, G., 2004).
Thus, according to many authors (Le Blanc S. J. 2014), antimicrobial therapy is not always effective enough due to the rapid habituation of microorganisms to drugs, stimulating the action of some of them on the development of pathogenic fungi, as well as their suppression of natural mechanisms of local and general antimicrobial protection. Although, as noted by other authors (Yang, H., Zhang, J., Xue, Z. et al. 2020), Antibiotics in comparison with other means give a better effect in many common animal diseases, The use of antibiotics promotes the development of resistance of microorganisms -this fact is indisputable, although there is a so-called "threshold" of antibiotic use, below which the selection of antibiotic-resistant bacteria does not occur, depending on the number of antibiotics, their dose and duration (Ghanem, M. E., Tezuka, E., Devkota, B., Izaike, Y., & Osawa, T., 2015). The exclusion of antibiotics from use does not always help reduce the number of resistant and return sensitive strains, oscillating microbes pass protection to other families (Le Blanc S. J., 2014). Absence in some cases of a positive result can be observed at late use of these means [13]. In the formation of stable associations of pathogens to combat them, it is necessary to use complex antibiotics (Yang, H., Zhang, J., Xue, Z. et al. 2020).
Some authors (Mohammed, Z. A., Mann, G. E., & Robinson, R. S., 2019) claim that the use of antibiotics in gynecological diseases completely eliminates the use of milk for food purposes, and even after pasteurization, it is suitable only for animal feed. Other authors believe (Dubuc, J., Duffield, T. F., Leslie, K. E., Walton, J. S., & LeBlanc, S. J., 2010) that the uterine wall has poor permeability to macromolecular structures, which include antibiotics. Thus, after intrauterine infusion of 3 g of tetracycline, the final amount in milk after 84 hours was less than 100 μg / kg. The lowest level of neurotoxicity that does not cause a visible effect of toxicological action is 100 μg / kg of animal weight per day, and this permissible daily use provides the necessary effectiveness of treatment (de Cássia Bicudo Therefore, the accumulation of pharmazone and tetracycline in the tissues and organs of animals treated, as well as their excretion in milk is relatively small.

Aims.
The main purpose of the research is to study the effectiveness of complex schemes of therapy of cows in acute postpartum purulent-catarrhal endometritis, in particular with the use of immunomodulatory drugs with simultaneous intrauterine administration of gel-based antibiotics.
To achieve this goal, the following tasks were set:  to study the reasons for the spread of obstetric pathology of cows in farms of Luhansk region, in particular the spread of chronic endometritis;  to conduct a comparative evaluation of the therapeutic efficacy of intrauterine use of gel-based antibiotics tetracycline and tilane and iodine bismuth sulphonamide emulsion in chronic endometritis in cows and to study the residual amount of antibiotics in milk after a course of antibiotic therapy.
 determine the cost-effectiveness of the proposed methods of treatment of cows with postpartum endometritis

Materials and Methods
The experiments were conducted during 2018 -2020 on cows of black-spotted breed in the conditions of LLC "Ryasnyanske" of Krasnopil district of Totaly region.
Cows were aged 4 -8 years with an average annual milk yield of 2.5 -3.1 thousand kg of milk per lactation.
Feeding rations of control and experimental groups of animals were not balanced or on individual indicators in accordance with feeding norms. Assessment of the postpartum period was performed according to the changes that occurred in the female reproductive system. This took into account not only the general condition of the animals, the nature of the exudate, the size and topography of the uterus, but also the condition of the ovaries, cervix and vagina in rectal and vaginal examinations. At rectal research paid attention also to the general reaction of an animal.
Diagnosis of various forms of endometritis was performed based on medical history, clinical and gynecological studies.
For the treatment of cows of the experimental group with postpartum endometritis, they were injected subcutaneously with 10 ml of the drug "Metrisan" in a mixture with 0.5% solution of novocaine at a rate of 1: 1. The interval between injections was 7-10 days. The frequency depended on the form of endometritis and was 3-5 injections (Tab. 1).
For the treatment of cows of the control group with postpartum endometritis they used a 10% solution of ichthyol intrauterine ly Injection of 7% solution of ichthyol into pararectal tissue The effectiveness of treatment was determined by the timing of clinical recovery of animals.
The gynecological examination consisted of external and internal examination. In the study by examination and palpation determined the condition of the abdominal wall, udder, the configuration of the root of the tail, the condition of the pelvic ligaments, vulva, withered crusts, the presence of exudate, its quantity, consistency and color. Vaginal and rectal examination was performed on prerecorded animals in the stall. When conducting a vaginal examination, the animal was placed in the direction of the daylight source. A pre-boiled vaginal mirror was used for work. The vagina, vaginal part of the cervix and anterior vagina were examined, paying attention to the color change of the mucous membrane, violation of its integrity: swelling of the cervical mucosa, overlays, scars, adhesions, cervical gaps, exudate from the uterus.
The cervix, body, uterine horns, ovaries, pelvic bones, and uterine mesentery were palpated rectally through the rectum. Examining the cervix, they paid attention to its location, size, consistency, mobility, pain, curvature. Palpation of the uterus determined the location, contractility, size, consistency and configuration of the horns, pain, presence, nature and number of discharges. Ovaries investigated, determining their shape, size, consistency, surface nature, mobility and soreness.
At rectal research paid attention also to the general reaction of an animal. Biochemical studies to determine the content in serum of total protein, seromucoids, glucose and triglycerides, sodium, potassium, calcium and phosphorus and alkaline phosphatase activity were performed in the laboratory of the Department of Surgery of SNAU.
Prevalence The causes of pathological birth in 2018 in this farm were: weakness of contractions and attempts -15 cases (12%), the wrong relationship between the fetus and the birth canal -2 cases (1.6%), delayed litter -13 cases (10.5% of total number of births) In 2019, the weakness of contractions and attempts -13 cases (9.8%), the wrong relationship between the fetus and the birth canal -1 case (0.8%), manure delay -8 cases (6%) (Tab. 3.). Table 3. In 2020, the number of cases of weakness of contractions and attempts -10 cases (7%), the wrong relationship between the fetus and the birth canal -1 case (0.7%), delayed litter -4 cases (2.8%).

The main causes of pathological birth in the economy
In the first place for the last 3 years among the causes of pathological birth is registered weakness of contractions and attempts -38 cases, 9.5%; then there is a delay of manure -25 cases, 6.3% of the total number of births for 3 years and the wrong relationship between the fetus and birth canal -4 cases, 1%. The most important among the pathologies of the postpartum period are endometritis, vaginitis, vulvitis, cervicitis and other gynecological diseases.
Study of indicators of postpartum pathology of cows, Analyzing this statistical report and the above material, we can conclude that the most common cause of culling was the pathology of the postpartum period, which once again indicated the relevance of our chosen topic and the feasibility of research in this area.

Dynamics of postpartum pathology of cows
Animals of the first group (control group) used uterine lavage with an Esmarch mug 0.1% aqueous solution of potassium permanganate -for 1, 2, 3, 4, 5 days for 2.5 liters. Furazolidone stick -from 1 to 5 days for 6 pieces, oxytocin -for 1, 3, 5, 7, 9, day 40 Units. Furazolidone rods have an antiseptic effect. Oxytocin activates the contraction of uterine smooth muscle and helps remove exudate. Tetravit -for 1 and 10 days for 15 ml. Tetravit compensates for the lack of vitamins in animals. Vitamin A, D3, E. Flushing the uterus with an Esmarch mug 0.1% aqueous solution of potassium permanganate -for 1, 2, 3, 4, 5 days for 2.5 liters. Potassium permanganate is an antiseptic. Amoxicillin twice a day at a dose of 40 ml, this is an antibiotic. The drug completely blocks the growth and development of bacteria.
Animals of the second group (experimental) were treated with the drug sepranol -intrauterine 2 tablets for 5 days, amoxicillin 150 -intramuscularly 50 ml. once. Sepranol has a broad antibacterial spectrum of action against most grampositive and gram-negative bacteria, protozoa and fungi, as well as provides anti-inflammatory action, improves proliferative

Вісник Сумського національного аграрного університету
Серія «Ветеринарна медицина», випуск 4 (51), 2020 processes in the genitals; propranolol hydrochloride -stimulates the activity of the uterus and is a beta-blocker adrenoceptor biometrics. Amoxicillin is a semi-synthetic antibiotic and has a broad spectrum of antimicrobial activity. The mechanism of action of amoxicillin is to disrupt the synthesis of mucopeptide, which is part of the cell wall of microorganisms, by inhibiting the enzymes transpeptidase and carboxypeptidase, which leads to osmotic imbalance and destruction of the bacterial cell. Table 5. Sepranol intrauterine, 2 tablets. The first 5 days. Amoxicillin 150 intramuscularly, in a dose of 50 ml, on the first day. 5

Scheme of the experiment
The results of the study conducted in the farm "Dubrava" located in the village of Ochkine Seredino-Bud district of Totaly region, it was found that the proposed therapy was effective in both the experimental and control groups (Tab.6). However, according to the results of the studies, the therapeutic efficacy was higher in the experimental group, where the therapy of cows with acute purulent-catarrhal endometritis using the drug sepranol and amoxicillin 150 was used.
The total number of days of infertility in the control group was 125 days, in the experimental -60 days. In terms of 1 head it is: in the control group -25 days, in the experimental -12 days.
The duration of the period from birth to fertilization in the control group is 55 days, in the experimental group -42 days.
Discussion of the results of research Acute postpartum purulent-catarrhal endometritis is one of the most common and dangerous diseases of cows, which brings huge economic losses to the economy. Diseases of the uterus not only negatively affect fertility, but also reduce all types of animal productivity. The disease begins to develop on the 5th -6th day after birth in the form of altered lochia from the uterus.
The pathological process in endometritis is localized in the mucous membrane and connective tissue. Once in the uterus, microbes irritate the tissues with the products of their vital activity. As a result of the action of microbes and their toxins, inflammation occurs, the spread of which depends on the virulence of microbes, the resistance of uterine tissues and its response to pathogenic factors.
The inflammatory process begins to develop with redness and swelling of the tissues. The vessels of the uterus dilate and overflow with blood, increased transudation leads to the development of edema. In the stage of hyperemia, the activity of oxidative processes in the tissues of the uterus increases sharply.
The disease occurs as a result of injury and infection of the uterus during birth, retention of manure, abortion, etc. Favorable factors are important: poor feeding, the predominance of acidic foods, mineral and vitamin deficiency of cows.
In the pathology of development for, prophylactic and therapeutic purposes use antibacterial and anti-inflammatory drugs. In the process of laboratory, clinical and industrial studies, the drugs have proven to be low-toxic and highly effective in diseases of acute postpartum purulent-catarrhal endometritis.
As a result of research, it was found that the use of the drug sepranol and amoxicillin-150 better treats and prevents the development of furazolidone sticks, tetravit.

Discussions
The transition from acute to chronic inflammation is very difficult to diagnose in time by clinical signs and even by immunological analysis ( Unbalanced diet in all respects, low quality of prepared feed, lack of mineral and vitamin supplements in the diet cause a decrease in blood levels of vital substances in all respects, especially carotene, which helps to suppress non-specific indicators of immunobiological protection and activation of micro florauterus. The main etiological factor in the occurrence of chronic endometritis in cows are pathogenic and opportunistic microorganisms, which, acting on the body together, enhance their virulence properties and cause a pathological process (Dahl-Pedersen, K., Herskin, M. S., Houe, H., & Thomsen, P. T. (2018)).
Given the participation of blood in physiological reactions that cause changes in cellular and humoral immune factors, depending on environmental conditions and pathology (chronic endometritis) (Elsayed, Doaa H., El-Azzazi, Fakhri E., Mahmoud, Yasmina K., Dessouki, Sherif M., &Ahmed, Eman A.), the morpho-biochemical and immunological parameters of clinically healthy and endometritis cows were determined. . Studies of morphological composition included counting the number of erythrocytes, leukocytes, leukogram output, and biochemical analysis of blood -determining the amount of hemoglobin, total protein and its fractions.
In sick cows there is a significant decrease in the content of erythrocytes and leukocytes. The appearance in the blood of animals with endometritis, basophils and young neutrophils, as well as an increase in the number of rod and segmental neutrophils indicates neutrophilia with a simple regenerative shift of the nucleus to the left, indicating the presence of purulent inflammation in the body (Ghanem, M. E., Tezuka, E., Sasaki, K., Takahashi, M., Yamagishi, N., Izaike, Y., &Osawa, T. (2016)). This is due to the fact that the main function of neutrophils is their participation in protecting the body from infectious and toxic effects (Stojkov, Yanne&Keyserlingk, Marina&Duffield, T. &Fraser, D.. (2020)). Neutrophils -the first protective barrier against the penetration of microorganisms into the internal environment of the body; they are able to function in inflammation not only as phagocytes, but also as a "secretory gland", maintaining homeostasis under conditions of infection by agents of various natures (Barański, W., Podhalicz-Dzięgielewska, M., Zduńczyk, S., &Janowski, T. (2012)).
Among the biochemical parameters we noted some differences. The amount of total protein, albumin and hemoglobin in the blood of sick cows was significantly reduced compared to clinically healthy animals. Hypoalbuminemia leads to metabolic disorders between the blood and the interstitial space, as well as to the disruption of the transport of hormones, vitamins and minerals (Ghanem, M. E., Tezuka, E., Sasaki, K., Takahashi, M., Yamagishi, N., Izaike, Y., &Osawa, T. (2016)). The increase in all fractions of globulins, in particular -globulins in chronic inflammation, is due to their participation in the defense mechanisms of the sick animal, and the increase in -globulins -due to the presence of lipoproteins in this fraction. Almost the same content of -globulins, which are mainly immunoglobulins, in our opinion, is characterized by the fact that the intensification of immunological processes was observed in the acute phase of inflammation, which is not typical in the transition of this process to chronic. All this led to a significant decrease in the protein ratio, that is, to dysproteinemia.
That is, analyzing the obtained data of clinically healthy and patients with chronic purulent-catarrhal endometritis, we conclude that in the body of patients there is a complex of immunological and morphobiochemical changes that cause the chronic course. These processes are associated with the development of a secondary immunodeficiency condition relative to the suppressor variant, caused by both the immunogenicity of microorganisms and their toxins, and morphological changes in tissue in the area of inflammation Абубакарі Ібрагім Кавла, аспірант, Сумський національний аграрний університет (м. Суми, Україна) Комплексні методи діагностики та профілактики послідових ускладнень у коров Досліди проводили протягом 2018 -2020 рр. на коровах чорної-рябої породи в умовах ТОВ «Ряснянське» Краснопільського району Сумської області.