Catad_tema Dysbacteriosis - articles

Intestinal bacteria, probiotics and prospects for their use in the treatment of diseases of the gastrointestinal tract

Yu.O. Shulpekova
Department of Propaedeutics of Internal Diseases, Faculty of Medicine, MMA named after THEM. Sechenov, Moscow Peculiarities of the composition and the role of intestinal symbiont bacteria in the maintenance of health are considered. The correctness of the use of the term “dysbacteriosis” in clinical practice is discussed; diseases and conditions are indicated, which are often mistakenly interpreted as dysbacteriosis. A brief review of diseases in which the effectiveness of some probiotics is confirmed by the results of comparative studies is given. Indications for the use of the modern combined probiotic preparation Linex, its advantages and dosing regimens are presented.

The history of studying the role of intestinal microflora in maintaining human health dates back to the end of the 19th century, when ideas about the disease as a consequence of intestinal “autointoxication” were developed.

But even today we have to admit that we still know little about the interaction of our body and the bacteria inhabiting it, and it is very difficult to assess the composition of the microflora that inhabits the gastrointestinal tract (GIT) from the standpoint of “norm” and “pathology”.

The composition and physiological significance of the intestinal microflora

More than 400 species of microorganisms live in the human gastrointestinal tract. The content of colony-forming units (CFU) in 1 ml of intraluminal contents increases from 10 2-3 to 10 11-12 as you move from the stomach to the colon. At the same time, the proportion of anaerobic microorganisms increases and their oxidative potential decreases.

Intestinal bacteria are represented by the main (dominant or resident), concomitant and residual populations.

The dominant population consists mainly of bacteria of the families Lactobacillus, Bifidobacteria and bacteroids.

The associated population is represented by Escherichia coli, eubacteria, fusobacteria, enterococci and peptococci.

The residual population includes yeast-like fungi, bacilli, clostridia, Proteus, and others. Some of these microorganisms have more or less pronounced pathogenic properties. It is generally accepted that no more than 15% of intestinal microbes have the characteristics of pathogenic or opportunistic pathogens in a healthy person.

In the upper gastrointestinal tract, the composition of the microflora is similar to that of the oropharynx; a significant proportion of it is represented by streptococci. In the distal direction, the content of lactobacilli gradually increases, and bifidobacteria predominate in the colon.

According to modern concepts, the main role in maintaining the normal physiological state of the microflora of the gastrointestinal tract is played by bacteria of the Lactobacillus and Bifidobacteria families, which are Gram-positive non-spore-forming anaerobes that do not have pathogenic properties. An important characteristic of these microorganisms is the saccharolytic type of metabolism. In the process of fermentation of carbohydrates under the action of enzymes of lactobacilli and bifidobacteria, short-chain fatty acids are formed - lactic, acetic, butyric, propionic. In the presence of these acids, the development of conditionally pathogenic strains, which for the most part have a proteolytic type of metabolism, is inhibited. The suppression of proteolytic strains is accompanied by the suppression of putrefactive processes and the suppression of the formation of ammonia, aromatic amines, sulfides, and endogenous carcinogens. Thanks to the production of fatty acids, the pH of the intestinal contents is regulated.

Short chain fatty acids play an important role in the regulation of metabolism. Entering the systemic circulation, they provide up to 20% of the body's daily energy needs, and also serve as the main energy supplier for the intestinal wall epithelium.

Butyric and propionic acids increase mitotic activity and regulate epithelial differentiation. Lactic and propionic acids regulate calcium absorption. Of great interest is their role in the regulation of cholesterol metabolism and glucose metabolism in the liver.

Lactobacilli and bifidobacteria synthesize amino acids, proteins, vitamins B1, B2, B6, B12, K, nicotinic and folic acids, substances with antioxidant activity.

Bacteria of the main population play an important role in the digestion of milk components. Lactobacilli and Enterococcus are able to break down lactose and milk proteins. The phosphoprotein phosphatase secreted by bifidobacteria is involved in the metabolism of casein. All these processes take place in the small intestine.

Species of lactobacilli that inhabit the intestines include: L. acidophilus, L. casei, L. bulgaricus, L. plantarum, L. salivarius, L. rhamnosus, L. reuteri. Among bifidobacteria, B. bifidum, B. longum, B. infantis are distinguished.

Of the aerobic microorganisms belonging to the concomitant population, a serious role in the microbial biocenosis of the intestine belongs to the non-hemolytic Escherichia coli, which produces vitamins (B1, B2, B6, B12, K, nicotinic, folic, pantothenic acids), participates in cholesterol metabolism, bilirubin, choline, bile and fatty acids, indirectly affects the absorption of iron and calcium.

With the expansion of knowledge about the characteristics of the vital activity of the intestinal microflora, the idea of its important role in maintaining the tension of local and systemic immunity becomes more and more clear.

In the intestines, there are protective mechanisms that prevent excessive reproduction and the introduction of microflora. These include the integrity of the epithelium and the brush border (the distance between the microvilli of which is less than the size of the bacteria), the production of immunoglobulin A, the presence of bile, the presence of Peyer's patches, etc.

Due to the production of substances with antibacterial activity (bacteriocins, short-chain fatty acids, lactoferrin, lysozyme), the normal microflora provides local protection against excessive reproduction of opportunistic pathogens and the introduction of pathogenic microorganisms. The presence of a constant microbial stimulus and contact with macrophages and lymphocytes in the area of Peyer's patches provide sufficient tension of local immunity, the production of immunoglobulin A and high phagocytic activity. At the same time, constant contact with immune cells underlies immunological tolerance.

Components of intestinal bacteria penetrate into the systemic circulation, thus maintaining the necessary degree of tension of systemic immunity and ensuring its "acquaintance" with the microflora of the environment.

However, even those intestinal bacteria that are considered non-pathogenic, lacking a distinct ability to adhere, invade, and produce toxins, are theoretically capable of causing damage to the intestinal wall, and possibly also a systemic infection, if local defense mechanisms fail. Therefore, the appointment of drugs based on intestinal bacteria (probiotics) should always be justified.

Causes of violations of the composition of the intestinal microflora

The composition of the intestinal microbial population, even in a healthy person, is subject to variability and, apparently, reflects the body's ability to adapt to the characteristics of nutrition and lifestyle, and climatic factors.

It should be recognized that the general concept of “dysbacteriosis”, which until recently was widely used to refer to violations of the composition of the intestinal microflora, does not fully reflect the essence of such changes, does not allow a clear diagnosis and determine the tactics of treatment.

So, it is possible to distinguish individual diseases and syndromes, which are often mistakenly interpreted as dysbacteriosis:

bacterial overgrowth syndrome;
antibiotic-associated diarrhea;
Clostridium difficile infection (pseudomembranous colitis);
irritable bowel syndrome;
"traveler's diarrhea";
disaccharidase deficiency;
intestinal candidiasis against the background of immunodeficiency states;
staphylococcal enteritis, etc.

Each of these diseases has its own cause, certain risk factors, clinical presentation, diagnostic criteria and treatment tactics. Of course, against the background of these diseases, secondary disorders of the microbial composition of the intestine can develop.

Perhaps the most common bacterial overgrowth syndrome in clinical practice is characterized by a decrease in the number of anaerobes (especially bifidobacteria), an increase in the total number of functionally defective forms of E. coli (“lactose-”, “mannitol-”, “indolo-negative”), the content of hemolytic forms E. coli and creating conditions for the reproduction of Candida spp.

The syndrome of excessive bacterial growth develops against the background of disorders of the luminal or parietal digestion (congenital enzyme deficiency, pancreatitis, celiac enteropathy, enteritis), the passage of intestinal contents (interintestinal fistulas, “blind loops” of the intestine, diverticula, peristalsis disorders, intestinal obstruction); decrease in the protective properties of the mucous membrane (anacid conditions, immunodeficiencies); iatrogenic effects on the intestinal microflora (the use of corticosteroids, cytostatics, especially in debilitated and elderly patients).

Excessive reproduction of bacteria is observed mainly in the small intestine, since the most favorable nutrient medium is created here. Manifestations of bacterial overgrowth syndrome, such as flatulence, rumbling, transfusion in the abdomen, loose stools, hypovitaminosis, weight loss, often come to the fore in the clinical picture of the main diseases listed above.

Tests confirming the presence of pathological disorders of the composition of the microflora

As in the diagnosis of other diseases, adequate methods must be used to assess changes in the intestinal microflora.

Sowing feces for dysbacteriosis, common in Russia, cannot be considered an informative test, especially since pathological changes in the microflora mainly affect the small intestine. This method is valuable in terms of ruling out intestinal infections as well as C. difficile infection.

The microbiological examination of the aspirate culture of the contents of the small intestine has a very high accuracy.

The breath test with 14C-xylose, hydrogen tests with lactulose and glucose can detect the presence of excessive bacterial growth in the intestine, but do not give an idea of the composition of the microflora.

Determination of the spectrum of fatty acids in feces by gas-liquid chromatographic analysis makes it possible to approximately estimate the quantitative ratio of various types of intestinal bacteria.

The use of probiotics

At the beginning of the 20th century, the great Russian scientist Mechnikov I.I. put forward a hypothesis that a high content of lactobacilli in the intestinal biocenosis is a necessary condition for human health and longevity. Mechnikov I.I. conducted experiments on the use of a living culture of bifidobacteria for medicinal purposes.

In subsequent years, the development of drugs based on microorganisms with beneficial properties, the so-called probiotics, continued.

As a potential therapeutic agent, lactobacilli initially attracted the most attention as the bacteria with the most well-studied beneficial properties. Since the 1920s culture L. acidophilus began to be used in the form of acidophilus milk for the treatment of diseases of the gastrointestinal tract, accompanied by constipation. Since the 1950s experience is accumulating in the use of L. acidophilus and other crops to prevent antibiotic-associated diarrhea.

With the development of microbiology, new information was obtained about the positive properties of bifidobacteria, E. coli, non-toxigenic lactic streptococcus - Streptococcus (or Enterococcus) faecium. Certain strains of these microorganisms and their combinations began to be included in probiotic preparations.

When studying the ability of microbes to adhere to epithelial cells of the small intestine, it was shown that the use of microorganisms in combination increases their ability to be fixed in the brush border zone.

The mechanisms of the therapeutic action of probiotics include: suppression of the growth of pathogenic microorganisms, restoration of the integrity of the epithelium, stimulation of the secretion of immunoglobulin A, suppression of the production of pro-inflammatory cytokines, and normalization of metabolic processes.

The modern approach to the development of such preparations implies, firstly, the use of microorganisms in combinations and, secondly, their release in encapsulated form, which allows long-term storage at normal temperature. Clinical and experimental studies have shown that under the influence of gastric juice and bile, probiotics lose up to 90% of their activity before entering the intestine. Methods are being developed to increase the survival of bacteria - due to their immobilization on porous microcarriers, the inclusion of nutrient medium components in the preparation.

Despite the “theoretically” competent development of probiotic preparations, not all of them are effective in practice. To date, data from many open and blind controlled studies have been accumulated, based on the results of which some conclusions have been drawn about the prospects for the use of certain types of microorganisms in various intestinal diseases.

It has been shown that L. rhamnosus strain GG has the greatest effect in the treatment of infectious gastroenteritis in children, and E. faecium SF68 in adults.

According to some reports, during the recovery period after viral gastroenteritis, it is advisable to prescribe drugs containing lactobacilli or their combinations with bifidobacteria and enterococcus; subspecies of bifidobacteria contribute to the speedy resolution after bacterial intestinal infections.

The ability to reduce the incidence of antibiotic-associated diarrhea has been established for the following bacteria in probiotics:

L. rhamnosus strain GG;
a combination of L. acidophilus and L. bulgaricus;
E. faecium SF68;
B. longum;
a combination of Lactobacillus and B. longum;
medicinal yeast Saccharomyces boulardii.

To reduce the frequency of side effects of anti-Helicobacter therapy, it is recommended to take probiotics containing L. rhamnosus and S. Boulardii at the same time, or a combination of L. acidophilus with Bifidobacterium lactis.

A combination of L. acidophilus, L. bulgaricus, and Streptococcus thermophilus proved to be effective in preventing traveler's diarrhea.

According to a meta-analysis, in the treatment of recurrent C. difficile infection (pseudomembranous colitis), a probiotic containing S. boulardii is most effective.

In irritable bowel syndrome, the effect of probiotics on the severity of symptoms such as bloating, pain, as well as the total number of manifestations was investigated. Efficiency of microorganisms E. faecium, L. plantarum, as well as mixture VSL#3 (combination of Bifidobacterium breve, B. longum, B. infantis, L. acidophilus, L. plantarum, L. casei, L. bulgaricus, S. thermophilus) has been demonstrated , mixtures of L. acidophilus, L. plantarum and B. breve and mixtures of L. Salivarius and B. infantis. However, these data were obtained on relatively small groups of patients, so they have not yet been reflected in international recommendations for the treatment of patients with irritable bowel syndrome.

There is an acute question about the possibility of using probiotics for the treatment and prevention of exacerbations in chronic inflammatory bowel diseases - ulcerative colitis and Crohn's disease. Given the undoubted role of endogenous microflora in maintaining epithelial integrity and controlling inflammation, as well as the potential toxicity of currently used immunosuppressants, high hopes are placed on probiotics as the “drugs of the future” in the treatment of inflammatory bowel diseases. Due to insufficiently large statistical material, the results of the studies conducted do not yet allow us to develop generally accepted recommendations for the inclusion of probiotics in standard treatment regimens. However, very encouraging data have been obtained regarding the ability of the complex probiotic VSL#3 to reduce the incidence of relapses of Crohn's disease. In ulcerative colitis, E. coli Nissle 1917 and Lactobacillus GG showed an effect in terms of maintaining remission; in terms of remission induction, very high doses of VSL#3 probiotic.

It should be understood that the appointment of probiotics is rarely effective in the absence of etiotropic and pathogenetic treatment of the underlying disease. Depending on the specific situation, surgical treatment may be required (for example, with afferent loop syndrome, inter-intestinal fistulas), the appointment of anti-inflammatory and antibacterial drugs, regulators of gastrointestinal motility (for example, with irritable bowel syndrome).

Many probiotic preparations are registered in Russia. However, the vast majority of them are not sufficiently up-to-date and do not contain species and strains of microorganisms for which evidence has been obtained from comparative studies. With the accumulation of experience, there has been a trend towards the use of combined probiotics.

Characteristics and application of Linex

In recent years, in the practice of Russian gastroenterologists, Linex, a combined preparation containing bacteria - representatives of the natural intestinal microflora: Bifidobacterium infantis v. liberorum, Lactobacillus acidophilus and non-toxigenic group D lactic streptococcus Streptococcus (Enterococcus) faecium. As noted above, these bacterial species have demonstrated clinical efficacy in the treatment of a number of intestinal diseases and are among the microorganisms that are particularly “hopeful” for future inclusion in chronic inflammatory bowel disease regimens. The cultures of microorganisms that are part of Linex are obtained by growing on media with the addition of antibiotics, therefore they are resistant to most antibacterial agents and are able to multiply even under conditions of antibiotic therapy. The resistance of the resulting strains to antibiotics is so high that it persists with repeated inoculations of 30 generations, as well as in vivo. At the same time, no transfer of genes of antibacterial resistance to other types of microorganisms was noted. This is very important from the point of view of the consequences of the use of Linex: both on the background of taking and after discontinuation of the drug, there is no danger of developing resistance to antibiotics from pathogenic bacteria and one's own microflora.

The therapeutic effect of Linex consists in the temporary replacement of the functions of the patient's own intestinal microflora in conditions of its suppression, in particular against the background of the use of antibiotics. The inclusion of lactobacilli, S. Faecium and bifidobacteria in Linex ensures the supply of “therapeutic” microflora to different parts of the intestine in quantitatively and qualitatively balanced ratios.

In a placebo-controlled study involving 60 adult patients suffering from antibiotic-associated diarrhea or diarrhea of \u200b\u200bunidentified etiology, taking Linex for 3-5 days was accompanied by normalization of the stool. In children, Linex has been shown to be highly effective in preventing and treating antibiotic-associated diarrhea that has already developed.

The use of Linex against the background of eradication anti-Helicobacter therapy improves the tolerance of antibiotics: it reduces the incidence of flatulence and diarrhea.

In the intestine, the microbial components of Linex not only have a eubiotic effect, but also perform all the functions of normal intestinal microflora: they are involved in the synthesis of vitamins B1, B2, B3, B6, B12, H (biotin), PP, K, E, folic and ascorbic acids. By lowering the pH of the intestinal contents, they create favorable conditions for the absorption of iron, calcium, and vitamin D.

Lactobacilli and lactic acid streptococcus carry out enzymatic breakdown of proteins, fats and complex carbohydrates, including have a substitution effect in lactase deficiency, which in most cases accompanies intestinal diseases.

Linex is available in capsules containing at least 1.2×10 7 live lyophilized bacteria.

The pharmacokinetics of the drug has been little studied due to the fact that at present there are no pharmacokinetic models for the study of complex biological substances in humans, consisting of components with different molecular weights.

For infants and children under 2 years of age, Linex is prescribed 1 capsule 3 times a day, for children 2-12 years old - 1-2 capsules 3 times a day, for children over 12 years old and adults - 2 capsules 3 times a day. The drug is taken after meals with a small amount of liquid. Do not drink hot drinks to avoid the death of living microflora.

Linex can be prescribed during pregnancy and breastfeeding. There are no reports of cases of Linex overdose.

Conclusion

Thus, probiotics, especially their combined preparations, are gradually taking an increasingly strong place in gastroenterology.

As the evidence base accumulates, they may provide doctors with a way to treat the patient, skillfully influencing his symbiosis with the bacterial world and minimal risk to the human body.

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The role and methods of bacteriological studies in the diagnosis of diseases of the gastrointestinal tract

Bacteriological studies

Bacteria and fungi are found in large numbers in the intestine and perform a number of important functions: vitamin-forming, protective (due to competition with opportunistic and pathogenic flora), digesting (due to the content of various enzymes in them). Activation in the intestine of any one group (putrid, fermentative or pathogenic) leads to a change in the normal ratio of microflora - dysbacteriosis. Dysbacteriosis complicates the course of most gastrointestinal diseases.

Drug dysbacteriosis (fungal, staphylococcal, Pseudomonas aeruginosa, Proteus), which develops during treatment with antibacterial drugs, often proceeds severely, with untimely diagnosis often leads to sepsis, shock, sometimes fatal.

The diagnosis of dysbacteriosis is made on the basis of a bacteriological examination of feces, i.e. by the method of sowing feces on nutrient media with further identification of microorganisms.

Detection of microbial contamination of the intestine. Microbial contamination of the intestine is characterized by overgrowth of opportunistic microorganisms (Escherichia, Klebsiella, Enterococcus, lactobacilli) and suppression of the growth of bifidobacteria and other microorganisms related to protective factors.

The main causes of overgrowth of opportunistic microorganisms

acute gastroenteritis or enterocolitis transferred in the recent past;
diseases accompanied by impaired digestion and absorption of food products in the small intestine (congenital or acquired deficiency of lactase, sucrase and other disaccharide hydrolysis enzymes, celiac disease (gluten deficiency), achlorhydria, achilia, secretory pancreatic insufficiency, biliary insufficiency);
diseases accompanied by a violation of the motor function of the small intestine (diverticula, intestinal strictures in Crohn's disease, radiation damage, after surgical operations on the abdominal organs; obstruction in tumors of the small intestine; intestinal dyskinesia, for example, in diseases of the biliary tract);
chronic diseases of the internal organs, accompanied by signs of immunodeficiency (HIV infection, diabetes mellitus, infectious diseases, scleroderma, etc.);
massive long-term therapy with broad-spectrum antibiotics.

As a result of microbial contamination of the intestine, structural changes in its mucous membrane occur (flattening of the villi, inflammatory infiltration of the lamina propria), which leads to a persistent violation of the absorption of water and food, the development of long-term, refractory to treatment, diarrhea and other dyspeptic disorders and the appearance of signs of malabsorption.

Bacteriological studies to detect bacterial overgrowth in the intestine

Identification of excessive bacterial growth in the intestine is possible in several ways, 2 of which are most informative:

bacteriological examination of jejunal aspirates;
hydrogen breath test.

Bacteriological examination of jejunal aspirates

With microbial contamination, it reveals a significant increase in the total number of microorganisms in 1 ml of intestinal juice (more than 100/ml), as well as the predominance of opportunistic microflora. For the study, a long two-meter polyethylene probe is used, which is inserted through an endoscope with a biopsy channel to a depth of about 35 cm further than the pylorus.

Hydrogen breath test

Belongs to a group of numerous indirect methods for determining bacterial colonization of the small intestine. It is based on the ability of most bacteria to enzymatically break down carbohydrates, during which hydrogen is formed, which, after being absorbed into the blood, is excreted from the body during respiration.

The study is carried out in the morning on an empty stomach. First, an initial sample of exhaled air is obtained, for this the patient takes a deep breath and maximum exhalation into the modified Haldane-Priestley tube. At the end of expiration, 30 ml of air is taken into a plastic syringe. Then the patient ingests 50 g of lactulose (or glucose). For 3 hours, every 20 minutes, samples of exhaled air (30 ml each) are collected in the described manner. All obtained samples are analyzed on a hydrogen analyzer.

Normally, the amount of hydrogen in the exhaled air increases moderately, and the peak of hydrogen concentration occurs after 2 hours or more from the start of the study. With excessive bacterial growth in the small intestine, the peak concentration of H 2 (more than 20 r / min) is usually reached within the first hour. The hydrogen breath test is quite simple and safe, although its sensitivity is lower than bacteriological examination of jejunal aspirate.

Microhelminthological methods are used to detect eggs or larvae of helminths. For the study, native smears or fixed stained preparations are prepared.

When examining enterobiasis, methods of scraping from the perianal folds with a wooden spatula or cotton swab are used. Preparations are prepared from scrapings, which are examined under a microscope.

To control the treatment, the entire portion of the feces is sent to the laboratory on the days of taking the antihelminthic.

X-ray methods of research

The X-ray method of examining the intestine gives an idea of the location of the various sections of the intestine, their shape, the state of the motor-evacuation function (tonus and peristalsis), allows you to identify inflammation in the intestinal mucosa, diagnose expansions or narrowings, determine changes in the relief of the mucous membrane and evaluate the motor activity of the intestine .

Main methods:

survey radiograph of the abdominal cavity;
artificial contrast;
through probe retrograde contrasting of the small intestine;
irrigoscopy;
double contrast colon.

Plain radiograph of the abdominal cavity in the vertical position of the patient	Most informative in the presence of symptoms of "acute abdomen": with dynamic or mechanical intestinal obstruction (horizontal fluid levels in the abdominal cavity); with perforation of the stomach or intestines (accumulation of gas under the dome of the diaphragm); with acute pancreatitis (segmental accumulation of gas in the jejunum and a symptom of the "watch loop").
Artificial contrasting of the esophagus, stomach and intestines by ingestion of an aqueous suspension of barium sulfate (“contrast breakfast”)	It is the most common method of X-ray examination of these organs. This method makes it possible to study the structure of the alimentary canal almost throughout its entire length, although the most valuable information can be obtained by examining the esophagus, stomach, and duodenum. Loops of the small intestine are filled with contrast within 3–5 hours, the caecum and ascending colon 6–9 hours, and the entire colon 24 hours after barium ingestion. With the help of oral administration of a contrast agent, it is impossible to achieve “tight” filling of the small and large intestine, therefore, it is possible to study only the relief of the mucous membrane and the motor function of the intestine, to diagnose various dyskinesias of the small intestine, acute enteritis, mechanical and dynamic obstruction of the small intestine, Crohn's disease.
Through the tube introduction of barium suspension into the jejunum or retrograde into the ileum	More informative and carried out in specialized gastroenterological clinics. With this method of research, uneven, intermittent narrowing of the intestine, deformation of its contours, wall rigidity, deep ulcers, strictures, fistulas, limited mobility of the intestinal wall, as well as graininess of the mucosal relief of the “cobblestone pavement” type are found.
Irrigoscopy	It is one of the main methods for diagnosing inflammatory processes and intestinal dysfunctions, intestinal malformations, malignant neoplasms and consists in retrograde administration of a contrast agent through the rectum using the Bobrov apparatus. This allows you to achieve tight filling of the colon and study in detail the position, shape, size and features of its contour. After defecation and emptying of the colon under conditions of low filling of the organ, the relief and minor pathological changes in the mucous membrane are studied. For better contrast, gas is additionally injected into the esophagus, stomach or large intestine (pneumography), and this technique is also combined with the introduction of gas (nitrous oxide, carbon dioxide) around the organ under study (parietography). Before irrigoscopy, it is necessary to conduct a digital examination of the rectum and sigmoidoscopy. Irrigoscopy is prescribed not earlier than 48-72 hours after sigmoidoscopy. Preparing the patient for irrigoscopy: exclude gas-producing foods from the diet (vegetables, fruits, dairy, yeast products, brown bread, fruit juices) and ensure plenty of fluids (up to 2 liters per day) 2-3 days before the study (to prevent flatulence and obtain a reliable result); take laxatives: 20-30 g of magnesium sulfate, 2-3 tab. bisacodyl or 30-60 ml of castor oil at 12.00-13.00 on the day before the study (thorough cleansing of the upper colon is ensured). If the patient has diarrhea, castor oil is contraindicated; the patient is allowed breakfast, lunch and dinner on the evening before the study (the resulting feces will be removed on the morning of the study using a cleansing enema); make 2 cleansing enemas - in the evening on the eve of the study and in the morning (no later than 2 hours before the study), with an interval of 1 hour (cleansing of the lower colon is provided); Escort the patient to the X-ray room at the appointed time. Execution of the procedure: using an enema, a suspension of barium sulfate (36–37 ° C) is injected up to 1.5 l, prepared in an X-ray room; take a series of pictures; warn the patient about a change in the color of feces and difficult bowel movements.
Double contrast method	Inflating the large intestine with air after introducing a small amount of barium into it is also used in the study of the large intestine.

Endoscopic methods of examination of the intestine

Colonoscopy

In recent years, due to the use of special flexible fiber optic endoscopes, colonoscopy has become one of the most important diagnostic methods.

Along with X-ray examination, endoscopy is currently considered as the main method for diagnosing diseases of the stomach and intestines at the earliest stages of their development.

Colonoscopy is used to diagnose the following diseases:

colon cancer;
nonspecific ulcerative colitis;
Crohn's disease with possible damage to the colon;
colon polyps with possible malignancy;
intestinal bleeding of unknown etiology.

Among all known instrumental research methods, only with endoscopy can one study in detail the smallest changes in the mucous membrane, recognize sources of bleeding, and dynamically monitor the course of pathological processes. In addition, with the help of endoscopy, it is possible to carry out various surgical and therapeutic manipulations directly under visual control.

The colonoscopy method is quite safe, but its implementation requires special skills due to the anatomical features of the large intestine, which has a number of natural curves and physiological sphincters. Before colonoscopy, it is advisable to conduct sigmoidoscopy and digital examination of the rectum.

The results of colonoscopy largely depend on the quality of the patient's preparation for the study.

Preparing the patient for a planned colonoscopy:

explain to the patient the purpose and course of the upcoming study and obtain his consent to the procedure (explain to the patient that during the procedure all intimate areas will be covered);
3 days before the study, a slag-free diet No. 4 is recommended (prevention of flatulence and ensuring a reliable study result);
the patient takes a solution of magnesium sulfate 25% 60 ml at 12.00–13.00 on the day before the study. Breakfast, lunch and dinner are allowed on the evening before the study;
on the evening before the study, several cleansing enemas are made (up to “clean water”);
make a cleansing enema in the morning, 2 hours before the study (an enema made more than 2 hours before the study does not provide the necessary cleansing of the intestinal mucosa by the time of the study; an enema made less than 2 hours before the study changes the state of the mucous membrane);
carry out premedication as prescribed by a doctor 20-30 minutes before the study;
take the patient to the endoscopy room.

The examination is carried out by the doctor in the position of the patient lying on the left side. After the study, the patient must be observed and rest.

If necessary, a targeted biopsy of the colonic mucosa can be performed during a colonoscopy.

Sigmoidoscopy

Through sigmoidoscopy, pathological changes in the mucous membrane can be detected (malignant and benign neoplasms, inflammatory processes, ulcerations, hemorrhoids, fistulas). During the study, you can get smears and scrapings from the mucous membrane for bacteriological and cytological examination, perform a biopsy, some therapeutic and surgical manipulations.

Preparing the patient for the study:

The examination is carried out by the doctor in the position of the patient on the back with raised and spread apart lower limbs (when using a flexible proctoscope) or knee-elbow position (when using a rigid proctoscope). The rectoscope is inserted to a depth of 25–30 cm.

After the study, the patient must be observed and rest.

Laparoscopy

Laparoscopy is a method of visual examination of the abdominal cavity through an endoscope (laparoscope) inserted through the abdominal wall. Examination of the abdominal cavity, if necessary, is combined with targeted biopsy of the liver and sometimes the pancreas.

Laparoscopy is performed for urgent diagnosis and emergency surgery (eg, peritonitis or ascites of unknown origin, suspected mesenteric thrombosis, and intestinal infarction), as well as for endoscopic abdominal surgery.

Laparoscopy allows you to determine the size of some abdominal organs, evaluate the nature of their surface, the color of the serous membrane, the presence of focal superficial formations, etc.

Since laparoscopy is an invasive method, it is performed only in a surgical hospital in compliance with all the rules of asepsis and antisepsis.

Contraindications for laparoscopy:

heart and severe respiratory failure;
acute myocardial infarction and unstable angina;
hemorrhagic diathesis, severe anemia, etc.

Table of contents of the subject "Bacteriological Examination of the Gastrointestinal Tract. Examination of the Genitourinary System.":

In the proximal parts of the esophagus can detect a small amount of bacteria living in the oropharynx, in the distal sections - staphylococci, diphtheroids, lactic acid bacteria, sarcins, Bacillus subtilis and candida. Bacteriological examination is carried out to identify pathogens of esophagitis. The main pathogens are HSV, CMV and fungi of the genus Candida.

for herpes infection indicate deep multiple small ulcers; with CMV infection, they are larger and tend to merge. Candida esophagitis is typical for patients with severe immunodeficiency. To isolate candida, biopsy specimens are taken during esophagoscopy, smears are microscopically stained by Gram, and the material is inoculated on nutrient media.

Bacteriological examination of the stomach

Bacteria in the stomach practically absent, or their number does not exceed 10 3 -10 4 ml of content, due to acidic pH. More bacteria are found in the pyloric part. With hypochlorhydria in the stomach, lactobacilli, sarcins, enterobacteria, aeruginosa, enterococci, spore-forming bacilli and various fungi are detected. Of particular importance is Helicobacter pylori, the causative agent of recurrent ulcerative gastroduodenitis.

For H. pylori detection The most optimal is the sampling of biopsy specimens during fibrogastroscopy. At food poisoning caused by S. aureus and B. cereus, study gastric lavage, which is examined immediately. The samples are centrifuged, the sediment is microscopically examined and cultured on nutrient media. If immediate analysis is not possible, the pH of the samples is adjusted to neutral values and frozen. The vomit is delivered to the laboratory on ice; they can be frozen if necessary.

480 rub. | 150 UAH | $7.5 ", MOUSEOFF, FGCOLOR, "#FFFFCC",BGCOLOR, "#393939");" onMouseOut="return nd();"> Thesis - 480 rubles, shipping 10 minutes 24 hours a day, seven days a week and holidays

Mikhailova, Olesya Nikolaevna Theoretical and practical aspects of the prevention and treatment of gastrointestinal diseases of calves in the early postnatal period: dissertation ... candidate of veterinary sciences: 06.02.02 / Mikhailova Olesya Nikolaevna; [Place of protection: Kur. state s.-x. acad. them. I.I. Ivanov].- [Kursk], 2013.- 159 p.: ill. RSL OD, 61 14-16/47

Introduction

1.0 Literature review 8

1.1 Gastrointestinal diseases of calves in the early postnatal period: etiology, clinical and epizootic features 8

1.2 Prevention and treatment of gastrointestinal diseases in calves 20

1.3 The use of immunostimulants in gastrointestinal diseases of newborn calves 31

2.0 Own research 34

2.1 Material and methods of research 34

3.0 Results of own research 36

3.1 Theoretical substantiation of the dissertation research methodology 36

3.2 Finding out the causes and characteristics of the course and manifestations of gastrointestinal diseases in newborn calves 38

3.3. Theoretical and experimental substantiation of obtaining a new immunometabolic drug based on succinic acid and levamisole 44

3.3.1 Study of the effect of a complex preparation (levamisole amber) on hematological, immunological and biochemical parameters of newborn calves 48

3.4 Effect of levamisole succinic on diarrhea rates 55

3.5 Efficacy of levamisole amber for correction of metabolic and immune processes in deep-calving cows 56

3.6 Production test of the effectiveness of levamisole amber for the prevention of gastrointestinal diseases in newborn calves 61

3.7 The effectiveness of complex preparations of succinic acid for the prevention and treatment of diarrhea in newborn calves when administered orally 68

3.7.1 Theoretical and experimental substantiation of the possibility of combined use of succinic acid, ASD of the second fraction of iodoinol 68

3.7.2 The effect of succinic acid in combination with ASD of the second fraction, in combination with iodinol, on hematological, immunological and biochemical parameters of clinically healthy calves when administered orally 70

3.7.3 Efficacy of oral administration of a formulation based on succinic acid and ASD for prevention and in combination with iodinol in the clinic for the treatment of diarrhea in newborn calves 73

3.7.4 Efficacy of oral administration of a composition based on succinic acid and ASD for prevention and in combination with iodinol in the treatment of diarrhea in newborn calves with severe toxic infection syndrome 75

3.8 Results of field experience in evaluating the effectiveness of scientific developments for the prevention of diarrhea in newborn calves 77

4.0 Discussion of research results 81

5.0 Conclusions 104

6.0 Practical suggestions 106

7.0 References 107

Appendix 143

Introduction to work

Relevance of the topic. Gastrointestinal diseases, manifested by diarrhea syndrome, are widespread and cause great economic damage to industrial livestock. Despite the great attention paid by science and practice to the problem of prevention and treatment of gastrointestinal diseases in calves, there is no significant improvement in the situation. Calves that have been ill with diarrhea at an early age are later stunted and, as a rule, are prone to respiratory pathology.

The leading cause of massive gastrointestinal diseases in newborn calves are infectious pathogens, the virulence of which increases when passed through the body of susceptible animals. In diarrhea of newborn calves, it is very difficult to determine the leading role of one or another pathogen. In this regard, attempts to prevent these diseases using specific agents do not always have a positive result. At the same time, the widely practiced use of chemotherapy and antibiotic therapy often leads to the selection of drug-resistant strains of microorganisms.

The resistance of calves to diarrhea is completely determined by the activity of colostral immunity, which is directly dependent on the quality of colostrum (Mishchenko V.A. et al. 2004). The data of recent years indicate that under the conditions of industrial animal husbandry in the colostrum of cows there is a sharp decrease in immune defense factors, as a result of which newborn calves have a deficiency of the humoral immune system (Voronin E.S., Shakhov A.G., 1999). Taking into account that disorders of metabolic and immune processes underlie the clinical manifestations of all pathophysiological conditions, the modern concept of prevention and treatment of gastrointestinal diseases should include the mandatory use of immunometabolic agents.

All of the above determined the choice of the topic of the dissertation research on the search for effective means of preventing and treating gastrointestinal diseases with diarrheal syndrome.

Purpose of research. The main goal of the dissertation research was the theoretical and experimental substantiation of the preparation and use of succinic acid preparations in the system of measures for the prevention and treatment of gastrointestinal diseases in calves with diarrheal syndrome.

To achieve this goal, the following tasks were identified:

To study the features of the manifestation and course of gastrointestinal diseases of newborn calves;

To theoretically and experimentally substantiate methods for obtaining complex preparations with immunometabolic and anti-infectious activity;

To study the effectiveness of the use of succinic acid preparations for stimulating immunobiochemical processes, preventing and treating gastrointestinal diseases in calves.

Determination of the production efficiency of the author's approaches to the prevention and treatment of diarrhea in calves.

Scientific novelty. New compositions of complex immunometabolic preparations based on succinic acid have been scientifically substantiated, developed and patented, and the effectiveness of their use for stimulating metabolic and immune processes, preventing dysbacteriosis, and treating diarrhea in calves of the early postnatal period has been determined.

The practical significance of the work. As a result of scientific research in practical veterinary medicine, cost-effective, simple and effective means and practical proposals for the prevention and treatment of gastrointestinal diseases in newborn calves have been proposed. The results of the research were included as an integral part of the project of temporary guidance on the use of levamisole amber, approved by the director of the Kursk Research Institute of Agro-Industrial Production of the Russian Agricultural Academy and the Veterinary Administration of the Kursk Region.

The main provisions of the dissertation submitted for defense:

1. Causes, features of the manifestation and course of gastrointestinal diseases in newborn calves;

2. Theoretical and experimental substantiation of obtaining new compositions with immunometabolic, anti-infective and detoxification activity.

3. The results of studying the effectiveness of the use of new drugs in the system of measures to stimulate metabolic and immune processes, prevent and treat gastrointestinal diseases in calves with diarrheal syndrome.

Approbation and publication of the results of the study. The materials of the dissertation research were reported and discussed at the International Scientific and Practical Conference of the Belgorod State Agricultural Academy "Problems of agricultural production at the present stage and ways to solve it" - Belgorod, 2012; at the International Scientific and Practical Conference of the Kursk State Agricultural Academy "Agro-industrial complex: contours of the future" - Kursk, 2012; at the International Don agrarian scientific and practical conference "Actual problems of ensuring the veterinary welfare of the livestock industry" - Zernograd, 2012; at the International scientific and practical conference "Actual problems of veterinary medicine and intensive animal husbandry" of the Bryansk State Agricultural Academy - Bryansk - 2013.

Based on the materials submitted for the defense of the dissertation, 7 articles were published, including 3 in peer-reviewed journals.

The structure and scope of the dissertation.

The dissertation work is presented on 143 pages of a computer text, illustrated with 24 tables, consists of an introduction, a literature review, own research and a discussion of their results, conclusions, proposals for production, a list of references. The list of used literature includes 344 sources, including 122 foreign authors.

Prevention and treatment of gastrointestinal diseases in calves

According to Samokhin V.T. et al. (2002), Shakhova A.G. (2002) The biological complex "mother-fetus-newborn" should be considered as a single system in the development of rational methods for the prevention and control of neonatal diseases, because there is a direct relationship between the state of metabolism, the level of natural resistance of the body of cows, intrauterine development of the fetus, the state of health and safety of newborn calves. This point of view is the result of numerous scientific studies carried out at different times by E.S. Voronin. (1981) with co-authors (1989), Devrishev D.A. (2000), Zaroza V.G. (1983), Kasicha A.Yu. (1987), Nemchenko M.I. et al. (1986), Semenov V.G. (2002), Sidorov M.A. (1981, 1987), Suleimanov S.M. (1999), Urban V.P., Neimanov I.L. (1984), Fedorov Yu .Sch1988), Chekishev V.M. (1985), Sharabrin I.G. (1974), Shishkov V.P. et al. (1981,1985), Shkil N.A. (1997) and others.

Even normally developed calves have a number of physiological characteristics that make them especially vulnerable to gastrointestinal diseases. First of all, it is a physiological immunodeficiency.

In newborns, the immune system is underdeveloped, they are characterized by low functional activity of the cellular and inferiority of the humoral immunity. Compensation for age-related deficiencies in the immune system of newborns in the postnatal period of life occurs due to cellular and humoral factors of colostrum. With their lack in colostrum, immunodeficiency is aggravated (Voronin E.S., Shakhov A.G., 1999; Devrishev D.A., 2000; Terekhov V.I., 2002; Fedorov Yu.N. 1988, etc.).

According to the vast majority of researchers, the resistance of calves to diarrhea is determined by the activity of colostral immunity, which is directly dependent on the quality of colostrum, which is the only source of immunoglobulins (Mishchenko V.A. et al., 2005; Richou R 1981; Salt LJ, 1985; Selman JE, 1979).

Along with antibodies from the mother, immunologically active leukocyte cells are transmitted to the newborn with colostrum (Vieg A. ea, 1971 Concha C. ea, 1980; Selman J. 1979; Suling L. 1980; Smith Y. ea. , 1977; Tough DFea, 1996).

With timely, no later than 2 hours after birth, drinking colostrum, the proportion of gamma globulins in blood plasma proteins reaches 30-50%, which significantly reduces the risk of diarrhea. Conversely, calves in which by the age of one day the amount of gamma globulins in the blood does not exceed 10% fall ill and almost all die.

The importance of timely feeding of colostrum to newborns is most indicative of the comparison of clinical data on the registration of diarrheal disease in calves "night" and "day". The incidence and death of calves born at night significantly exceeds the indicators for "day" calves (Mishchenko V.A. et al., 2005). Feeding colostrum to calves "nightlights" is carried out in the morning, that is, after 5-6 or more hours.

Immediately after calving, colostrum should be checked for mastitis. The most important factor in the prevention of neonatal diarrhea is the timing of colostrum feeding. The best time for the first watering is when the calf develops a sucking reflex (most 30-40 minutes after birth). For mastitis in a mature cow, colostrum from other cows can be used. It is recommended to have a frozen colostrum bank.

An important factor influencing the level of colostral immunity is the concentration of immunoglobulins in colostrum (Weaver D.e.a. 2000). In high-yielding cows, the concentration of immunoglobulins in colostrum is lower than in animals with lower milk yield. In cows with impaired metabolic processes, calves are born with a similar metabolic symptom complex. Violations of the immunometabolic status in the mother has a direct impact on the embryonic development of the fetus, which can be one of the causes of the development of secondary immunodeficiencies, and as a result of high morbidity.

The next feature that affects the propensity for the incidence of diarrhea is the sterility of the intestine at birth. The calf is born weakly protected and, getting into a new environment saturated with various pathogens, is easily infected.

The main route of infection of newborn calves is alimentary, as a result of contact with the so-called "shed" microflora, represented by an association of gram-negative and gram-positive microorganisms.

Conditionally pathogenic (“shed”) microflora decomposes milk in the stomach with the formation of a large amount of toxins that irritate the intestinal mucosa.

The phenomenon of dysbacteriosis reflects the conditions for the reproduction of lactic acid and opportunistic microorganisms that have changed in the intestine. The latter, penetrating into the abomasum, displace lactic acid microorganisms. The rapid reproduction of conditionally pathogenic microorganisms is accompanied by the formation of a large number of toxic products of their vital activity.

To compensate for physiological dysbacteriosis and earlier formation of intestinal colonization resistance after the first colostrum giving to newborn calves, it is recommended to prescribe probiotics (Antipov V.A., 1981; Bazhenov A.N. et al., 1986; Voronin E.S. et al., 1994; Grigoriev G. I. et al., 2000; Gryazneva T. N., 2005; Gudkov A. V. et al., 1986; Devrishev D. A., 1988; Intizarov M. M., 1989; Karpov V. N., 1987; Kvasnikov E. I. et al., 1975; Panin A. N. et al., 1988; Perdigon G. e. a. 2001; Shanahan F., 2001 and others).

Probiotics are biological preparations that are stabilized cultures of symbiotic microorganisms or their fermentation products that have antagonistic activity against putrefactive and pathogenic microorganisms, incl. and to Escherichia, in the intestines.

The multicomponent composition and versatile pharmacological action allow the use of probiotics with a high effect for the prevention and treatment of calf colibacillosis, dysbacteriosis, detoxification of individual endogenous and exogenous toxins, creation of nonspecific intestinal protection against pathogenic bacteria (intestinal colonization resistance). These are environmentally safe, physiological drugs in terms of pharmacokinetics and pharmacodynamics, technologically advanced for group use, do not have side effects, do not accumulate in organs and tissues of animals, do not cause addiction from pathogenic microflora (V.A. Antipov, 2001; A. Panin et al. ., 1993; Yu. N. Proskurin, 2000; S. Parnikova, 2002).

Early administration of probiotic preparations to newborn calves is also important because the normal intestinal microflora acts as the first stimulant of the immune system. It should be noted that the therapeutic efficacy of probiotics in gastrointestinal diseases of calves is not high enough. A contraindication to the use of probiotics is the inadmissibility of their combination with antibiotics or other antimicrobial drugs.

A starvation diet is prescribed when signs of frequent bowel movements appear. Exclude 1-3 (at the discretion of the veterinarian) feeding with colostrum (milk), replacing it with electrolyte-energy solutions (in the amount of 0.5-1.0 l) or decoctions (infusions) of medicinal plants (R.J. Bywater, 1983). To prevent dehydration and intoxication of sick calves, a large number of different electrolyte solutions have been proposed for both drinking and parenteral administration.

Means of chemo-antibiotic therapy remain the main group of drugs used in these pathologies.

Antibacterial drugs are etiotropic drugs that selectively inhibit the growth of microorganisms, which determines their most important property - specificity in relation to pathogens of infectious diseases in calves. The most important place among these drugs is occupied by antibiotics. Kovalev V.F. et al. (1988),. Vitebsky E.L. et al. (1998), Sokolov V.D. et al. (2000), Troshin A.N. et al. (2003):

Among the highly effective, antidiarrheal agents are drugs of the nitrofuran series. Possessing a wide range of bioactivity, nitrofurans, unlike antibiotics, are able to increase the overall resistance of the macroorganism (Shipitsyn A.G. et al., 1999).

As a result of the mass and often unsystematic use of this group of drugs, their effectiveness has noticeably decreased. The main reason for this is the accumulation of drug-resistant strains of opportunistic microorganisms in nature.

To overcome the drug resistance of microorganisms, a combination of two drugs and a combination of antibacterial therapy with drugs that enhance the body's defenses are most often practiced.

Study of the effect of a complex preparation (levamisole amber) on hematological, immunological and biochemical parameters of newborn calves

In this series of experiments, the composition of the drug was used, including: 1% succinic acid and 2% levamisole. We illustrate the method of obtaining a complex preparation with the following example.

To prepare a complex preparation, 950 ml of demineralized water was used, in which 10.0 g of succinic acid and 20 g of levamisole were successively dissolved when heated. The total volume was adjusted to 1000 ml. by adding demineralized water. The resulting solution had pH = 4.5-4.7. After packaging the drug in vials, sterilization was carried out. Sterilization by autoclaving in the mode of 1.0-1.1 atm. within 30 minutes did not change the physico-chemical properties of the drug. The precipitate did not fall out during storage for 12 months.

The research and production experience was carried out at the Kalininsky SGJ.

The objectives of the research included studying the effect of the drug (levamisole amber) on the hematological, immunological and biochemical parameters of normotrophic calves and hypotrophic calves.

Taking into account the clinical material at our disposal, 4 groups of calves were formed for the experiment. The first two groups were formed from physiologically developed calves. In two more groups, calves of the same age were selected, but from among hypotrophics.

Thus, by conducting the first series of experiments, we had the opportunity to study the effect of the drug on the body of physiologically developed calves and animals with obvious signs of immunodeficiency. The latter was confirmed by the data of background homeostasis, selected for the experiments of calves, displayed in tables 4,5,6,7.

As expected, even the first control results of the studies showed that hematological parameters, even in physiologically developed calves, were at the lower values of the physiological norm for this age group. The use of levamisole amber made it possible to activate metabolic processes, expressed in an increase and normalization of hemoglobin levels in normotrophic calves. In the hypotrophic calves of the experimental group, the level of hemoglobin content and the number of erythrocytes practically reached the background indicators of clinically healthy peers. When conducting subsequent studies (after 2 weeks), there were no significant changes in calves from the control groups over this period of time.

The study of the level of total protein and protein fractions in the blood serum of calves found that their content at the beginning fluctuated within the lower limits of the physiological norm. The use of levamisole amber already on the third day revealed a trend towards an increase in total protein and y - globulins, which reached their maximum value on the 7th day, after which there was a tendency for a gradual decrease. However, on the 14th day of control studies, the total protein content and gamma globulin fraction were significantly higher than those of their peers from the control groups (P 0.05). In the process of research, a slight increase in the level of albumins, fractions of a- and p-globulins was also noted.

Thus, the use of levamisole amber contributed to the improvement of hematological parameters and protein metabolism.

An increase in the level of gamma globulin fraction indicated an increase in the body's resistance.

The use of the drug allowed to significantly improve the biochemical parameters of blood (table 7). So, after 2 weeks in physiologically developed calves, the content of total calcium in the blood serum after was 3.02±0.11, against 2.41±0.19 in control animals (P 0.05); and in calves - hypotrophic, respectively 2.28±0.10 and 1.57±0.18 (Р 0.005). The content of inorganic phosphorus also had a pronounced growth trend. Thus, in normotrophic calves, the content of inorganic phosphorus increased on day 7 to 2.04 ± 0.15, on day 14 to 2.09 ± 0.16, which was 11.3% and 12.4% higher than in animals of the control group. A similar pattern was observed in terms of the content of inorganic phosphorus in normotrophic calves. Normalization of calcium-phosphorus metabolism significantly improved the alkaline reserve of the blood. Thus, in normotrophic calves, it increased from 29.4 ± 2.3 to 43.7 ± 3.1 vol% CO2 (on day 14), and in hypotrophic calves from 14.3 ± 2.1 vol% CO2 to 29.1±2.8 vol% CO2. The increase and normalization of the content of calcium, phosphorus and reserve alkalinity of the blood could not but indicate an improvement in the mineral metabolism in general, which is important in terms of increasing the overall resistance of the organism. Clinical observations indicated that the animals of the experimental groups grew better and were more calm than their peers from the control groups. The average increase in live weight of clinically healthy calves was 307 g, and in control calves - 250 g. In general, the absolute increase in live weight of clinically healthy experimental calves was 9.2 + 0.3 kg, against 7.5 + 0.4 kg in control calves, and in developmentally lagging 5.0 ± 0.2 kg and 2.4 kg, respectively. +0.2 kg (Table 8).

As you know, one of the factors of nonspecific defense of the body is phagocytosis. When analyzing the results of the phagocytic reaction, it was found that already on the 3rd day, the phagocytic activity of neutrophils in both clinically healthy and hypotrophic patients was 13% and 5.8% higher than before the administration of the drug, and 12% and 5.2% higher, according to compared with control animals.

The bactericidal and lysozyme activity of blood serum, reflecting, in general, the humoral mechanisms of natural resistance, already on the 3rd day after immunization was higher than in control animals (table 9).

The dynamics of immunological parameters indicates that levamisole amber provided a pronounced tendency to increase the phagocytic activity of neutrophils and the bactericidal activity of blood serum. On the 14th day, these indicators did not undergo pronounced changes.

The effect of succinic acid in combination with ASD of the second fraction, in combination with iodinol, on hematological, immunological and biochemical parameters of clinically healthy calves when administered orally

For experiments, we used a composition based on 1% succinic acid, 4% ASD of the second fraction in combination with iodinol in a ratio of 3:1. Three groups of calves were formed according to the principle of analogues in SPK Kalininsky. The first experimental group (n=5) was given an amber biostimulant, the second (n=5) an amber biostimulant in combination with iodinol. The third group (n=5) was the control group. The calves of this group were fed an aqueous solution of iodinol (3:1). The drugs were drunk in a volume of 100 ml, once a day for 5 days, 30 minutes before drinking milk.

Blood sampling for research was carried out before, on the third and fourteenth days after drinking the drugs. In tables - 19, 20,21 we provide information on the dynamics of hematological, immunological and biochemical studies.

The results of hematological studies indicated that the use of succinic acid preparations had a positive effect on the level of erythrocytes and their saturation with hemoglobin. The level of hemoglobin content on days 3 and 14 after the course of drug use was significantly higher in experimental calves in relation to their peers from the control group.

The index of reserve alkalinity in calves of the control groups in all periods of the study was below the physiological norm, while in animals of both experimental groups it was within the physiological parameters. This indicated that oral administration of succinic acid preparations ensured the elimination of metabolic acidosis. The elimination of metabolic acidosis had a positive effect on protein metabolism. The level of total protein in the blood of calves of the experimental groups was within the average physiological parameters, while in their peers it was slightly above the lower limit.

In the control periods of the studies after the course of using the drugs in calves of both experimental groups, the indicators of bactericidal and lysozyme activity were significantly higher than in individuals from the control group. This indicated a positive effect of succinic acid preparations on natural resistance factors, which is important in relation to the body's resistance to endogenous infection, including diarrhea.

Results of industrial experience in evaluating the effectiveness of scientific developments for the prevention of diarrhea in newborn calves

Based on the fact that the resistance of newborn calves to diarrhea is completely determined by the activity of colostral immunity, which directly depends on the quality of colostrum, an important role should be given to the health of deep-calving cows. However, the data of retrospective studies, including those conducted by us, indicate that deep pathobiochemical processes develop in most cows in the last months of pregnancy. Metabolic and immune processes are interconnected. This circumstance served as the basis for the development of a complex drug with immunometabolic activity. In the course of scientific and production experience, it was found that the use of levamisole amber provides an effective correction of metabolic and immune processes in deep-calving cows and calves. This had a positive impact on the incidence of diarrhea in newborn calves.

In turn, the oral administration of iodinol, an amber biostimulant, turned out to be an effective approach for the relief of diarrheal syndrome in newborn calves.

Research and production experience was carried out in the SPK "Kalininsky" in the period from January to May 2013. The procedure for conducting scientific and industrial experience included carrying out preventive measures both on deep-calving cows and on newborn calves.

Deep-calving cows and newborn calves up to 10 days of age were the object for conducting research and production experience.

During the course of preventive immunometabolic therapy, we were guided by the already approved scheme for the use of levamisole amber, which provides for three intramuscular administration of the drug to deep-calving cows in a volume of 10.0 ml with an interval of 10 days.

In the event of diarrhea in calves, drinking colostrum or milk was replaced by giving iodinol - amber biostimulant (100 ml) mixed with saline with simultaneous single administration of levamisole amber at a dose of 2.0 ml. The concentration of succinic acid in the preparation used for cows and calves was 1.5%.

From among the deep-calving cows, two experimental groups were formed. The cows of the experimental group (n=103) were treated with levamisole amber. The control group included 95 cows.

Based on the results of clinical observation of calves, the following data were obtained, which are presented in table 24.

During clinical observation, it was found that the disease of diarrhea in calves obtained from cows of the control group in March and April was recorded in almost all animals. At the same time, diarrhea often proceeded with symptoms of severe intoxication.

In calves born from cows of the experimental group, diarrhea proceeded mainly in mild and moderate severity.

It should be noted this feature. In calves born from cows in the control group, diarrheal syndrome usually developed on 2 less than 3 days. While in calves born from cows of the experimental group, diarrhea appeared on the 5-6th day.

For the treatment of diarrhea, we used iodinol-amber biostimulator. At the same time, it was found that a single feeding of iodinol, an amber biostimulant, to calves with symptoms of mild diarrhea, as a rule, was sufficient to stop it. With an average severity of the course of diarrhea, two, less often three, drinking of this composition was required with an interval of 5-6 hours.

In the clinic for the treatment of diarrhea with a pronounced toxic symptom complex, intravenous administration of 100 ml of Reamberin (1.5% succinic acid solution) with the addition of 50 ml of 40% glucose to its composition turned out to be very effective. The choice of Reamberin to relieve the symptoms of toxicosis is not accidental. The detoxification solution "Reamberin" contains 1.5% succinic acid in the form of its salt - sodium succinate. The practical use of "Reamberin" in medicine and veterinary medicine indicates that it has an exceptionally high therapeutic effect in toxicoinfectious diseases. However, the experience of its use indicates that it can also have side effects on the cardiac and respiratory systems. For infusions, it is used intravenously, drip. It is obvious that the drip administration of the drug to productive animals is difficult to perform under production conditions.

According to the results of our observations, the inclusion of glucose in the composition of the infusion solution made it possible to reduce the risk of side effects of Reamberin on the cardiovascular and respiratory systems with a slow (through a thin needle) jet method of administration. This composition was tested by us on 17 calves. No side effects were observed in any of the cases.

The results of the use of Reamberin in combination with glucose provided a favorable "break" of the intoxication syndrome. As a rule, after the first administration of the infusion composition, the clinical condition of the calves improved so much that it no longer raised concerns about an unfavorable outcome. It should be noted that the use of other infusion solutions, in particular glucose-salt solutions, in the clinic for the removal of toxic syndrome did not give such a pronounced positive effect.

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