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Exopeptidases and endopeptidases

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Enzyme preparations

The use of enzymes for therapeutic purposes is called enzyme therapy. In clinical practice, the most widely used enzymes are animal enzymes, which are formed under the influence of genes. More than 2000 enzymes produced by animal cells have already been discovered, which regulate the basic life processes of cells (synthesis and destruction of substances, their transformation, intracellular respiration, energy exchange).

Enzymes are protein substances with a molecular weight of 21,000 and above.

Their activity depends on their chemical structure. The use of enzymes as pharmacological agents can cause allergic reactions upon first administration or upon repeated administration (between the 7th and 14th day after the drug enters the body), when antibodies accumulate in the body. Therefore, the clinical use of enzyme preparations should be carried out taking into account the characteristics of the reactivity of the child’s body, and should not be administered parenterally for more than 7 days.

In pediatric practice, enzyme preparations are used quite widely for purulent-necrotic processes, collagenosis, diseases of the bronchopulmonary system, insufficient function of the digestive glands and other diseases.

22.Means that stimulate regeneration processes. Classification. The concept of the main groups of drugs: vitamins (B-12, B-6, B-1, C, A, U, etc.), anabolic drugs (steroidal and non-steroidal drugs - riboxin, potassium orotate, sodium nucleinate, methyluracil, etc. ), biogenic stimulants (aloe, FIBS, etc.), immunomyodulators (levamisole, thymalin, tactivin, etc.), nonspecific stimulants of plant and animal origin (sea buckthorn oil, rose hip oil, carotoline, propolis, solcoseryl, cerebrolysin, etc.). Application in dentistry.

As a result of diseases, injuries, adverse environmental influences, excessive physical and mental stress, cell damage, disruption of their nutrition (trophism) and a deficiency of energy necessary for biosynthetic processes can occur. All this leads to dysfunction or death of cells and tissues consisting of them.

During the life of the body, there is constant regeneration (restoration, revival) of cells that have expired or are damaged as a result of disease, injury, excessive stress, and so on. Physiological regeneration is a natural process of replacing short-lived cells (blood cells, skin cells, mucous membranes), which is stimulated by internal mechanisms. The building materials for this process are the constituent elements of food.

In many cases, physiological regeneration does not ensure restoration of the original structure and function of organs and systems, and it becomes necessary to resort to artificial stimulation of regeneration. Regeneration aimed at restoring areas of organs or tissues that have died as a result of some pathological process is called reparative. Reparative regeneration includes a set of measures to eliminate the damaging agent, non-viable tissues, factors inhibiting regeneration (stress, inflammation, infection, impaired blood supply, and so on). The complex of these measures also includes stimulation of protein synthesis and activation of protective mechanisms that ensure the functioning of the body as a whole.

To stimulate regeneration, medications with different mechanisms of action are used to accelerate recovery processes in the body. These agents activate the body's metabolism and immune system, stimulate protein synthesis, improve the absorption of oxygen by cells and tissues, and have a tonic effect on the functions of the central nervous and endocrine systems. These include vitamins (folic acid, cyanocobalamin, pyridoxine, thiamine, ascorbic acid, retinol and others), anabolic agents (inosine, methandienone, methyluracil, nandrolone, sodium deoxyribonucleate, orotic acid, silabolin), immunomodulators, as well as various biogenic stimulants, obtained from plants, animal tissues and other natural sources, capable of accelerating or stimulating regeneration processes. Vitamins, anabolic agents, immunomodulators and their role in regeneration processes are discussed in the relevant sections. Biogenic stimulators of regeneration include aloe preparations (juice and extract), sea buckthorn oil, rosehip oil, propolis, apilak, various extracts from animal tissues, as well as products formed in estuary mud and peat.

Local, antimicrobial action and the use of concentrated and weak acids (boric, salicylic, etc.), features of use in dentistry. Toxic effect of concentrated acids, help with it.

ACIDS

The action depends on the strength and concentration of the acid.

A) weak acids have annoying action: dilate blood vessels and increase blood supply. In medicine, 1-2% solutions and 2-4% salicylic acid ointments are used, which have a keratoplastic effect => treatment of dermatitis in children.

B) As the concentration increases, surface coagulation of proteins is observed => antiseptic effect=> weak acids are used as antiseptics, including for washing, rinsing, and douching. Boric acid is used more often, but it is contraindicated in children under 3 years of age, because in young children it is well absorbed and causes serious poisoning (decreased blood pressure, renal failure).

C) strong acids cause coagulative necrosis– cell dehydration. Necrosis is of dense consistency with clear boundaries, not deep. Practically not infected. In dermatology, HNO3 is used to eliminate papillomas.

D) HCl (hydrochloric acid) is used in gastroenterology for gastritis with insufficient secretory activity.

D) Limontar contains succinic and citric acid.

Stimulates energy metabolism

Stimulates OBprocesses

Increases the secretion of gastric juice

Increases appetite

Regulates tissue metabolism

Has an anti-alcohol effect

Application:

1) to increase the nonspecific reactivity of the body of pregnant women, in order to prevent complications from hypoxia and fetal malnutrition, and in case of miscarriage.

2) to prevent intoxication, reduce the toxic effects of alcohol during acute alcohol intoxication. For chronic alcoholism in the complex treatment of binge drinking

3) for the treatment of asthenovegetative disorders.

Acids and alkalis– cause denaturation of microorganism proteins. They pass through cell membranes in an undissociated form, and their dissociation takes place inside the microbial cell, where they cause denaturation of protein components.

Compounds that dissociate in aqueous solutions to form cations (positively charged hydrogen ions) and anions (negatively charged ionic acid residues). According to the degree of dissociation, they are divided into strong - with pronounced dissociation (50%, nitric, sulfuric, hydrochloric), medium (from 1 to 50%, phosphoric) and weak (1%, boric) acids.

Antimicrobial actions are associated with changes in the pH of the environment, dehydration of bacterial cells and the formation of albuminates. However, they are rarely used for disinfection of livestock buildings, with the exception of lactic and peracetic acids, due to equipment damage and high cost.

Locally, acids act on tissues anti-inflammatory (due to astringent and antiseptic effects), irritating and necrotic (depending on the acid and concentration).

When taken orally in low concentrations, they increase the activity of pepsin, enhance the separation of gastric and pancreatic juices, and have an anti-fermentation effect.

Antidotes for acid poisoning are weak alkalis.

Boric acid- Acidum boricum. Colorless fine crystalline powder or flakes. Soluble in cold (1:25) and easily (1:4) in boiling water.

Used externally as an antiseptic in the form of solutions for inflammation of the mucous membranes. It is also prescribed in the form of powders (with talc, salicylic acid, zinc oxide, etc.) and ointments for skin lesions.

Salicylic acid It is used externally as an antiseptic, distracting, irritant, keratoplastic and keratolytic agent.

In weak (up to 5%) concentrations, salicylic acid acts antiseptically, soothes inflammatory processes, enhances epithelization (keratoplastic effect), and relieves itching. Usually used in a weaker concentration, 1–2%.

At a concentration of more than 5–10%, salicylic acid dissolves the upper stratum corneum of the epidermis (has a keratolytic effect) and helps remove crusts and scales. Salicylic acid has a particularly strong keratolytic effect in concentrations of more than 10%. The use of occlusive dressings, compresses with ointments containing salicylic acid significantly enhances its keratolytic effect.

Alkaline preparations. Their local and resorptive (sodium bicarbonate) action, application. Possibility of use in dentistry. Toxic effect of caustic alkalis, measures of assistance.

Compounds whose aqueous solutions contain a hydroxyl anion - OH, which determines their action. Of the alkalis, the most active are hydroxides, then carbonates and the weakest are bicarbonates. Hydroxides have a strong bactericidal and cauterizing effect, bicarbonates have a slight antimicrobial and anti-inflammatory effect. The mechanism of antimicrobial action is associated with a change in the pH of the environment, dehydration of bacterial cells, protein denaturation and the formation of alkaline albuminates with proteins.

When applied to the skin, they penetrate into tissues and, depending on the drug and concentration, dissolve hair and cause tissue necrosis (sodium and potassium hydroxides). In weak concentrations (up to 0.5%) they exhibit a disinfectant and cleaning effect.

They neutralize acids in the stomach, cause liquefaction of mucus, delay pancreatic secretion and accelerate the evacuation of stomach contents. They are quickly neutralized in the blood. The buffer equilibrium is restored due to the release of excess bicarbonates and alkaline phosphate and the conversion of ammonia to urea. Excreted through the respiratory tract, they help to liquefy bronchial mucus and act as an expectorant.

Used as disinfectants, antiseptics, detergents and medicinal agents.

Strong alkalis can cause damage to the skin and mucous membranes. The affected areas are washed with weak solutions of acids, which are administered orally in case of oral alkali poisoning. In case of extensive lesions, painkillers or sleeping pills are prescribed as antishock agents. According to indications, symptomatic treatment is carried out.

Sodium bicarbonate(sodium bicarbonate, bicarbonate of soda, purified soda, drinking soda) - Natrii hydrocarbonas. White crystalline powder, soluble in water (1:12).

Used as a weak antiseptic (for rhinitis, stomatitis, vaginitis) in the form of a solution and inhalation.

A good antacid used to neutralize excess stomach acid. However, this can lead to the formation of CO2 and distension of the stomach. Used as an expectorant in combination with other expectorants. Included in artificial Carlsbad salt.

Acute poisoning with strong alkalis is characterized by signs of their local and resorptive action. Providing first aid for poisoning with caustic alkalis is in many ways similar to measures of assistance for poisoning with acids and differs only in that a 5% solution of acetic, citric or lactic acid is used to neutralize alkalis on the skin. Gastric lavage, prevention and treatment of painful shock are carried out in the same way as for acid poisoning. In order to eliminate alkalosis, they resort to inhalation of carbon dioxide and parenteral administration of sodium chloride.

Antacids.

Antacids

Antacids are weak bases that can neutralize HC1 and increase the pH of the stomach to 4.0 - 4.5.

Food antacids – milk.

Medicines: – weak bases (aluminum hydroxide), salts of strong bases and weak acids (magnesium oxide, sodium bicarbonate, calcium carbonate).

The effect of the drugs is short-term: 0.5 - 1 hour on an empty stomach and about 2 hours after meals.

Mechanism of action:

Neutralizes acid in gastric juice

· influencing the receptors of the duodenum, they reflexively inhibit the secretion of gastric juice

· By increasing the pH of gastric contents, pepsin activity is reduced.

Absorbable antacids – Sodium bicarbonate– quickly neutralizes HC1. For the systematic use of sodium bicarbonate is of little use, since when it interacts with HC1 it forms CO 2, which stimulates the secretion of HC1. In addition, sodium bicarbonate is well absorbed in the intestine and can cause alkalosis.

Non-absorbable antacids:

Magnesium oxide– neutralizes HC1 without the formation of CO 2. 3-4 times more active than sodium bicarbonate. Interacting with HC1, it forms MgC1 2, which has laxative properties. Small amounts of Mg 2+ ions can be absorbed and, in case of renal failure, have a resorptive effect (lower blood pressure).

Aluminum hydroxide– neutralizes HC1 and has enveloping and weak adsorbing properties. It is believed that A1(OH) 3 stimulates the synthesis of prostaglandins E and I 2 and promotes the formation of mucin and has a weak gastroprotective effect. The drug may cause constipation. Binds phosphates and prevents their absorption. A small amount of Al 3+ is absorbed and, in case of renal failure, can cause manifestations of osteodystrophy, myopathy, encephalopathy, and kidney damage, so the duration of treatment should not exceed 2 weeks.

In medical practice, combinations of Mg(OH) 2 and A1(OH) 3 are used - the drugs “Almagel”, “Maalox”. When treating peptic ulcers, these drugs are taken after meals after 1 hour (in the first hour, food plays a buffer role) and after 3 hours (to neutralize the secondary wave of secretion); Be sure to prescribe an antacid at night.

Antacids apply for heartburn, hyperacid gastritis, reflux esophagitis, peptic ulcer (reduce pain, and when used systematically can contribute to scarring of the ulcer).

Digestion occurs under the action of proteases - peptide hydrolases. Proteases that hydrolyze peptide bonds inside the molecule are endopeptidases, terminal amino acids are exopeptidases.

Specificity of protease action. Trypsin preferentially hydrolyzes peptide bonds formed by the carboxyl groups of arginine and lysine. Chymotrypsins are most active against peptide bonds formed by carboxyl groups of aromatic amino acids. Carboxypeptidases A and B are zinc-containing enzymes that cleave off C-terminal amino acid residues. Moreover, carboxypeptidase A preferentially cleaves off amino acids containing aromatic or hydrophobic radicals, and carboxypeptidase B cleaves off arginine and lysine residues. The last stage of digestion, the hydrolysis of small peptides, occurs under the action of the enzymes aminopeptidases and dipeptidases, which are synthesized by the cells of the small intestine in an active form.

Dipeptidases break down dipeptides into amino acids, but do not act on tripeptides.

As a result of the sequential action of all digestive proteases, most food proteins are broken down into free amino acids.

Endopeptidases (endoproteinases) proteolytic enzymes (pepsin, trypsin, chymotrypsin) that cleave peptide bonds within the peptide chain. They hydrolyze bonds formed by certain amino acids at the highest speed.

Exopeptidases (exoproteinases) are enzymes that hydrolyze proteins by cleaving amino acids from the end of the peptide: carboxypeptidases from the C-terminus, aminopeptidases from the N-terminus, dipeptidases cleave dipeptides. Exopeptidases are synthesized in the cells of the small intestine (aminopeptidases, dipeptidases) and in the pancreas (carboxypeptidase). These enzymes function intracellularly in the intestinal epithelium and, in small quantities, in the intestinal lumen.

Exopeptidases cleave off terminal amino acids, freeing them from the burden of the peptide bond, VIVA LA RESISTANCE!!!

Pepsinogen is a protein consisting of one polypeptide chain with a molecular weight of 40 kDa. Under the influence of HCl, it is converted into active pepsin (with an optimum pH of 1.0-2.5. During the activation process, as a result of partial proteolysis, 42 amino acid residues are cleaved from the N-terminus of the pepsinogen molecule, which contain almost all the positively charged amino acids present in pepsinogen. Thus, negatively charged amino acids are predominant in active pepsin, which are involved in conformational rearrangements of the molecule and the formation of the active center.

Activation of pancreatic enzymes. The proenzymes of a number of proteases are synthesized in the pancreas: trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidases A and B. In the intestine, they are converted through partial proteolysis into active enzymes trypsin, chymotrypsin, elastase and carboxypeptidases A and B.

Activation of trypsinogen occurs under the action of the intestinal epithelial enzyme enteropeptidase. This enzyme cleaves off the hexapeptide Val-(Asp)4-Lys from the N-terminus of the trypsinogen molecule. A change in the conformation of the remaining part of the polypeptide chain leads to the formation of an active center, and active trypsin is formed. The sequence Val-(Asp)4-Lys is inherent in most known trypsinogens of various organisms - from fish to humans.

(?) 76. Diagnostic value of biochemical analysis of gastric and duodenal juice. Give a brief description of the composition of these juices.

Gastric juice is a complex digestive juice produced by various cells of the gastric mucosa. Gastric juice contains hydrochloric acid and a number of mineral salts, as well as various enzymes, the most important of which are pepsin, which breaks down proteins, chymosin (rennet), which curds milk, and lipase, which breaks down fats. A component of gastric juice is also mucus, which plays an important role in protecting the gastric mucosa from irritating substances that enter it; when the acidity of gastric juice is high, mucus neutralizes it. In addition to hydrochloric acid, enzymes, salts and mucus, gastric juice also contains a special substance - the so-called. Castle's internal factor. This substance is necessary for the absorption of vitamin B12 in the small intestines, which ensures the normal maturation of red blood cells in the bone marrow. In the absence of Castle factor in gastric juice, which is usually associated with stomach disease, and sometimes with its surgical removal, a severe form of anemia develops. Analysis of gastric juice is a very important method for studying patients with diseases of the stomach, intestines, liver, gallbladder, blood, etc.

Duodenal juice is the digestive juice of the duodenum, consisting of pancreatic secretion, bile, juice of intestinal crypts and duodenal glands.

(?) 77. Pancreatic proteinases and pancreatitis. The use of proteinase inhibitors for the treatment of pancreatitis.

Pancreatitis is an inflammation of the pancreas. The disease can occur in an acute (quick and violent) or chronic (long and sluggish) form, with periods of exacerbation of chronic pancreatitis.

Causes of pancreatitis

Alcohol consumption and gallbladder diseases (primarily cholelithiasis) are the causes of pancreatitis in 95-98% of cases.

Other risk factors that can trigger inflammation of the pancreas:

Normally, the pancreas produces inactive enzyme precursors - their transition to the active form occurs directly in the duodenum, where they enter through the pancreatic duct and the common bile duct.

Under the influence of various factors (for example, a stone blocking the bile duct), the pressure in the pancreatic duct increases, the outflow of its secretions is disrupted, and premature activation of enzymes occurs. As a result, instead of digesting food, the enzymes begin to digest the pancreas itself. Acute inflammation develops.

In chronic pancreatitis, normal pancreatic tissue is gradually replaced by scar tissue, and insufficiency of the exocrine (production of enzymes) and endocrine (production of hormones, including insulin) functions of the gland develops.

In 1930, Frey discovered the first kallikrein inhibitor. Subsequently, this substance was obtained in its pure form and used for medicinal purposes. In clinical practice, protease inhibitors trasylol, contrical, tsalol, pantrypin, etc. are widely used for the treatment of acute pancreatitis. Trasylol is a polypeptide with a molecular weight of 11,600, consisting of 18 amino acids. It inhibits kallikrein, trypsin, chymotrypsin and plasmin by forming an inactive complex with the enzymes. In addition, trasylol and other protease inhibitors have a pronounced vasopressor effect and are thus important in preventing shock. Under the influence of Trasylol, according to various authors, the pain syndrome is quickly relieved, toxemia and symptoms of shock are reduced. When prescribing large doses of one of the protease inhibitors, we also in most cases observed an improvement in the condition of seriously ill patients (disappearance of pain, etc.). However, treatment has always been complex and it is difficult to say how much protease inhibitors helped in these cases.

Rental block

The content of free amino acids in food products is very low. The overwhelming majority of them are part of proteins that are hydrolyzed in the gastrointestinal tract under the action of protease enzymes (peptide enzymes). The substrate specificity of these enzymes lies in the fact that each of them cleaves peptide bonds formed by certain amino acids at the highest speed. Proteases that hydrolyze peptide bonds inside a protein molecule belong to the group of endopeptidases. Enzymes belonging to the group of exopeptidases hydrolyze the peptide bond formed by terminal amino acids. Under the influence of all gastrointestinal proteases, food proteins break down into individual amino acids, which then enter tissue cells.

Digestion of proteins in the stomach

Gastric juice is the product of several types of cells. The parietal cells of the stomach walls produce hydrochloric acid, the main cells secrete pepsinogen. Accessory and other gastric epithelial cells secrete mucin-containing mucus. Parietal cells also secrete a glycoprotein into the gastric cavity, which is called “intrinsic factor” (Castle factor). This protein binds the “external factor” - vitamin B12, prevents its destruction and promotes absorption.

Formation and role of hydrochloric acid. The main digestive function of the stomach is that it begins the digestion of protein. Hydrochloric acid plays a significant role in this process. Proteins entering the stomach stimulate the release of histamine and a group of protein hormones - gastrins, which, in turn, cause the secretion of HCI and the proenzyme - pepsinogen. The source of H+ is H2CO3, which is formed in the parietal cells of the stomach from CO2 diffusing from the blood and H2O under the action of the enzyme carbonic anhydrase (carbonate dehydratase):

H2O + CO2 → H2CO3 → HCO3- + H+

Dissociation of H2CO3 leads to the formation of bicarbonate, which, with the participation of special proteins, is released into the plasma in exchange for C1-, and H+ ions, which enter the lumen of the stomach through active transport catalyzed by membrane H+/K+-ATPase. In this case, the concentration of protons in the lumen of the stomach increases 106 times. Cl- ions enter the lumen of the stomach through the chloride channel. The concentration of HCl in gastric juice can reach 0.16 M, due to which the pH value is reduced to 1.0-2.0. Ingestion of protein foods is often accompanied by the release of alkaline urine due to the secretion of large amounts of bicarbonate during the formation of HCl. Under the influence of HCl, food proteins that have not been subjected to heat treatment are denatured, which increases the availability of peptide bonds for proteases. Hcl has a bactericidal effect and prevents pathogenic bacteria from entering the intestines. In addition, hydrochloric acid activates pepsinogen and creates an optimal pH for the action of pepsin.

The mechanism of pepsin activation. Under the influence of gastrins, the synthesis and secretion of pepsinogen, an inactive form of pepsin, is stimulated in the main cells of the gastric glands. Pepsinogen is a protein consisting of one polypeptide chain with a molecular weight of 40 kDa. Under the influence of HCl, it is converted into active pepsin (molecular weight 32.7 kDa) with an optimum pH of 1.0-2.5. During the activation process, as a result of partial proteolysis, 42 amino acid residues are cleaved from the N-terminus of the pepsinogen molecule, which contain almost all the positively charged amino acids present in pepsinogen. Thus, negatively charged amino acids are predominant in active pepsin, which are involved in conformational rearrangements of the molecule and the formation of the active center. The active pepsin molecules formed under the influence of HCl quickly activate the remaining pepsinogen molecules (autocatalysis). Pepsin primarily hydrolyzes peptide bonds in proteins formed by aromatic amino acids (phenylalanine, tryptophan, tyrosine) and somewhat more slowly - formed by leucine and dicarboxylic amino acids. Pepsin is an endopeptidase, therefore, as a result of its action, shorter peptides are formed in the stomach, but not free amino acids.

Digestion of proteins in the intestines.

Gastric contents (chyme) enter the duodenum during digestion. The low pH value of chyme causes the release of the protein hormone secretin in the intestine, which enters the blood. This hormone in turn stimulates the release of pancreatic juice containing HCO3- from the pancreas into the small intestine, which leads to the neutralization of gastric juice HCl and inhibition of pepsin. As a result, the pH increases sharply from 1.5-2.0 to ∼7.0. The entry of peptides into the small intestine causes the secretion of another protein hormone - cholecystokinin, which stimulates the release of pancreatic enzymes with an optimum pH of 7.5-8.0. Under the action of pancreatic enzymes and intestinal cells, protein digestion is completed.

Activation of pancreatic enzymes The pancreas synthesizes proenzymes of a number of proteases: trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidases A and B. In the intestine, they are converted through partial proteolysis into active enzymes trypsin, chymotrypsin, elastase and carboxypeptidases A and B.

Activation of trypsinogen occurs under the action of the intestinal epithelial enzyme enteropeptidase. This enzyme cleaves off the hexapeptide Val-(Asp)4-Lys from the N-terminus of the trypsinogen molecule. A change in the conformation of the remaining part of the polypeptide chain leads to the formation of an active center, and active trypsin is formed. The sequence Val-(Asp)4-Lys is inherent in most known trypsinogens of various organisms - from fish to humans.

The resulting trypsin activates chymotrypsinogen, from which several active enzymes are obtained (Fig. 9-3). Chymotrypsinogen consists of one polypeptide chain containing 245 amino acid residues and five disulfide bridges. Under the influence of trypsin, the peptide bond between the 15th and 16th amino acids is cleaved, resulting in the formation of active π-chymotrypsin. Then, under the influence of π-chymotrypsin, the dipeptide ser(14)-arg(15) is cleaved, which leads to the formation of δ-chymotrypsin. Cleavage of the dipeptide tre(147)-arg(148) completes the formation of a stable form of the active enzyme - α-chymotrypsin, which consists of three polypeptide chains connected by disulfide bridges. The remaining proenzymes of pancreatic proteases (proelastase and procarboxypeptidases A and B) are also activated by trypsin through partial proteolysis. As a result, active enzymes are formed - elastase and carboxypeptidases A and B.

Specificity of protease action. Trypsin preferentially hydrolyzes peptide bonds formed by the carboxyl groups of arginine and lysine. Chymotrypsins are most active against peptide bonds formed by carboxyl groups of aromatic amino acids (Phen, Tyr, Tri). Carboxypeptidases A and B are zinc-containing enzymes that cleave off C-terminal amino acid residues. Moreover, carboxypeptidase A preferentially cleaves off amino acids containing aromatic or hydrophobic radicals, and carboxypeptidase B cleaves off arginine and lysine residues. The last stage of digestion, the hydrolysis of small peptides, occurs under the action of the enzymes aminopeptidases and dipeptidases, which are synthesized by the cells of the small intestine in an active form.

• Aminopeptidases sequentially cleave off the N-terminal amino acids of the peptide chain. The best known is leucine aminopeptidase, a Zn2+- or Mn2+-containing enzyme, despite its name, which has broad specificity for N-terminal amino acids.
• Dipeptidases break down dipeptides into amino acids, but do not act on tripeptides.

As a result of the sequential action of all digestive proteases, most food proteins are broken down into free amino acids.

Exopeptidases (exoproteinases) enzymes that hydrolyze proteins by cleaving amino acids from the end of the peptide: carboxypeptidases from the C-terminus, aminopeptidases from the N-terminus, dipeptidases cleave dipeptides. Exopeptidases are synthesized in the cells of the small intestine (aminopeptidases, dipeptidases) and in the pancreas (carboxypeptidase). These enzymes function intracellularly in the intestinal epithelium and, in small quantities, in the intestinal lumen.

Endopeptidases (endoproteinases) proteolytic enzymes (pepsin, trypsin, chymotrypsin) that cleave peptide bonds within the peptide chain. They hydrolyze bonds formed by certain amino acids at the highest speed. Endopeptidases are synthesized as proenzymes, which are then activated by selective proteolysis. Thus, cells secreting these enzymes protect their own proteins from destruction. The cell membrane of animal cells is also protected from the action of enzymes by the surface layer of oligosaccharides - the glycocalyx, and in the intestines and stomach - by a layer of mucus.

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This topic belongs to the section:

Biological chemistry

Metabolism in the human body. Proteins, amino acids, fats. Catabolism and anabolism. Biochemical processes. Subject biological chemistry. Exam Questions and Answers.

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Subject and tasks of biological chemistry. Metabolism and energy, hierarchical structural organization and self-reproduction as the most important signs of living matter

Multimolecular systems (metabolic chains, membrane processes, biopolymer synthesis systems, molecular regulatory systems) as the main objects of biochemical research

Levels of structural organization of living things. Biochemistry as the molecular level of studying life phenomena. Biochemistry and medicine (medical biochemistry)

Main sections and directions in biochemistry: bioorganic chemistry, dynamic and functional biochemistry, molecular biology

History of the study of proteins. The idea of ​​proteins as the most important class of organic substances and a structural and functional component of the human body

Amino acids that make up proteins, their structure and properties. Peptide bond. Primary structure of proteins

Dependence of the biological properties of proteins on the primary structure. Species specificity of the primary structure of proteins (insulins from different animals)

Conformation of peptide chains in proteins (secondary and tertiary structures). Weak intramolecular interactions in the peptide chain; disulfide bonds

Basics of protein functioning. The active center of proteins and its specific interaction with the ligand as the basis of the biological function of all proteins. Complementarity of interaction between protein molecules and ligand. Reversibility of binding

Domain structure and its role in the functioning of proteins. Poisons and drugs as protein inhibitors

Quaternary structure of proteins. Features of the structure and functioning of oligomeric proteins using the example of heme-containing protein - hemoglobin

Lability of the spatial structure of proteins and their denaturation. Factors causing denaturation

Chaperones are a class of proteins that protect other proteins from denaturation under cellular conditions and facilitate the formation of their native conformation

Variety of proteins. Globular and fibrillar proteins, simple and complex. Classification of proteins according to their biological functions and families: (serine proteases, immunoglobulins)

Immunoglobulins, structural features, selectivity of interaction with antigen. Diversity of antigen-binding sites of H- and L-chains. Classes of immunoglobulins, features of structure and functioning

Physicochemical properties of proteins. Molecular weight, size and shape, solubility, ionization, hydration

Methods for isolating individual proteins: precipitation with salts and organic solvents, gel filtration, electrophoresis, ion exchange and affinity chromatography

Methods for quantitative measurement of proteins. Individual characteristics of the protein composition of organs. Changes in the protein composition of organs during ontogenesis and diseases.

History of the discovery and study of enzymes. Features of enzymatic catalysis. Specificity of enzyme action. Dependence of the rate of enzymatic reactions on temperature, pH, enzyme and substrate concentration.

Classification and nomenclature of enzymes. Isoenzymes. Units for measuring enzyme activity and quantity.

Enzyme cofactors: metal ions and coenzymes. Coenzyme functions of vitamins (for example, vitamins B6, PP, B2)

Enzyme inhibitors. Reversible and irreversible inhibition. Competitive inhibition. Drugs as enzyme inhibitors.

Regulation of enzyme action: allosteric inhibitors and activators. Catalytic and regulatory centers. Quaternary structure of allosteric enzymes and cooperative changes in the conformation of enzyme protomers.

Regulation of enzyme activity by phosphorylation and dephosphorylation. Participation of enzymes in the conduction of hormonal signals

Differences in the enzyme composition of organs and tissues. Organ-specific enzymes. Changes in enzymes during development

Changes in enzyme activity in diseases. Hereditary enzymopathies. The origin of blood enzymes and the significance of their determination in diseases

The use of enzymes to treat diseases. The use of enzymes as analytical reagents in laboratory diagnostics (determination of glucose, ethanol, uric acid, etc.). Immobilized enzymes

Metabolism: nutrition, metabolism and excretion of metabolic products. Organic and mineral food components. Major and minor components

Basic nutrients: carbohydrates, fats, proteins, daily requirement, digestion; partial interchangeability when feeding

Essential components of essential nutrients. Essential amino acids; nutritional value of various food proteins. Linoleic acid is an essential fatty acid

History of the discovery and study of vitamins. Classification of vitamins. Functions of vitamins.

Alimentary and secondary vitamin deficiencies and hypovitaminosis. Hypervitaminosis. Examples

Minerals of food. Regional pathologies associated with insufficiency of microelements in food and water.

Concept of metabolism and metabolic pathways. Enzymes and metabolism. The concept of metabolic regulation. Major end products of human metabolism

Studies on whole organisms, organs, tissue sections, homogenates, subcellular structures and at the molecular level

Endergonic and exergonic reactions in a living cell. Macroergic compounds. Examples.

Oxidative phosphorylation, P/O ratio. The structure of mitochondria and the structural organization of the respiratory chain. Transmembrane electrochemical potential.

Regulation of the electron transport chain (respiratory control). Dissociation of tissue respiration and oxidative phosphorylation. Thermoregulatory function of tissue respiration

Energy metabolism disorders: hypoenergetic states as a result of hypoxia, hypo-, avitaminosis and other reasons. Age characteristics of the body's energy supply with nutrients

Formation of toxic forms of oxygen, the mechanism of their damaging effect on cells. Mechanisms for eliminating toxic oxygen species

Catabolism of basic nutrients - carbohydrates, fats, proteins. The concept of specific pathways of catabolism and general pathways of catabolism

Oxidative decarboxylation of pyruvic acid. Sequence of reactions. Structure of the pyruvate decarboxylase complex

Citric acid cycle: sequence of reactions and characteristics of enzymes. Relationship between common catabolic pathways and the electron and proton transport chain

Mechanisms of regulation of the citrate cycle. Anabolic functions of the citric acid cycle. Reactions that replenish the citrate cycle

The main carbohydrates of animals, their content in tissues, biological role. Basic carbohydrates of food. Digestion of carbohydrates

Aerobic breakdown is the main pathway of glucose catabolism in humans and other aerobic organisms. Sequence of reactions before the formation of pyruvate (aerobic glycolysis)

Distribution and physiological significance of aerobic glucose breakdown. The use of glucose for the synthesis of fats in the liver and adipose tissue.

Anaerobic breakdown of glucose (anaerobic glycolysis). Glycolytic oxidation, pyruvate as a hydrogen acceptor. Substrate phosphorylation. Distribution and physiological significance of this glucose breakdown pathway

Biosynthesis of glucose (gluconeogenesis) from amino acids, glycerol and lactic acid. The relationship between glycolysis in muscles and gluconeogenesis in the liver (Cori cycle)

An idea of ​​the pentose phosphate pathway of glucose transformations. Oxidative reactions (up to the stage of ribulose-5-phosphate). Distribution and summary results of this pathway (pentose formation, NADPH and energetics)

Properties and distribution of glycogen as a reserve polysaccharide. Biosynthesis of glycogen. Glycogen mobilization

Features of glucose metabolism in different organs and cells: red blood cells, brain, muscles, adipose tissue, liver.

An idea of ​​the structure and functions of the carbohydrate part of glycolipids and glycoproteins. Sialic acids

Hereditary disorders of monosaccharide and disaccharide metabolism: galactosemia, fructose and disaccharide intolerance. Glycogenoses and aglycogenoses

The most important lipids of human tissues. Reserve lipids (fats) and membrane lipids (complex lipids). Fatty acids in human tissue lipids.

Essential nutritional factors of lipid nature. Essential fatty acids: ω-3- and ω-6-acids as precursors for the synthesis of eicosanoids.

Biosynthesis of fatty acids, regulation of fatty acid metabolism

Chemistry of reactions of β-oxidation of fatty acids, energy summary

Dietary fats and their digestion. Absorption of digestion products. Digestion and absorption disorders. Resynthesis of triacylglycerols in the intestinal wall

Chylomicron formation and fat transport. The role of apoproteins in the composition of chylomicrons. Lipoprotein lipase

Biosynthesis of fats in the liver from carbohydrates. Structure and composition of transport lipoproteins in the blood

Deposition and mobilization of fats in adipose tissue. Regulation of fat synthesis and mobilization. The role of insulin, glucagon and adrenaline

The main phospholipids and glycolipids of human tissues (glycerophospholipids, sphingophospholipids, glycoglycerolipids, glycosphygolipids). An idea of ​​the biosynthesis and catabolism of these compounds.

Disorders of the metabolism of neutral fat (obesity), phospholipids and glycolipids. Sphingolipidoses

Structure and biological functions of eicosanoids. Biosynthesis of prostaglandins and leukotrienes

Cholesterol as a precursor to a number of other steroids. Concept of cholesterol biosynthesis. Write the course of reactions before the formation of mevalonic acid. The role of hydroxymethylglutaryl-CoA reductase

Synthesis of bile acids from cholesterol. Conjugation of bile acids, primary and secondary bile acids. Removing bile acids and cholesterol from the body.

LDL and HDL - transport, forms of cholesterol in the blood, role in cholesterol metabolism. Hypercholesterolemia. Biochemical basis for the development of atherosclerosis.

The mechanism of gallstone disease (cholesterol stones). The use of chenodesokeicholic acid for the treatment of cholelithiasis.

Digestion of proteins. Proteinases - pepsin, trypsin, chymotrypsin; proenzymes of proteinases and mechanisms of their conversion into enzymes. Substrate specificity of proteinases. Exopeptidases and endopeptidases.

Diagnostic value of biochemical analysis of gastric and duodenal juice. Give a brief description of the composition of these juices.

Pancreatic proteinases and pancreatitis. The use of proteinase inhibitors for the treatment of pancreatitis.

Transamination: aminotransferases; coenzyme function of vitamin B6. Specificity of aminotransferases

Amino acids involved in transamination; special role of glutamic acid. Biological significance of transamination reactions. Determination of transaminases in blood serum in myocardial infarction and liver diseases.

Oxidative deamination of amino acids; glutamate dehydrogenase. Indirect deamination of amino acids. Biological significance.

Kidney glutaminase; formation and excretion of ammonium salts. Activation of renal glutaminase during acidosis

Biosynthesis of urea. Relationship between the ornithine cycle and the TCA cycle. Origin of the nitrogen atoms of urea. Disturbances in the synthesis and excretion of urea. Hyperammonemia

Exchange of nitrogen-free residue of amino acids. Glycogenic and ketogenic amino acids. Synthesis of glucose from amino acids. Synthesis of amino acids from glucose

Transmethylation. Methionine and S-adenosylmethionine. Synthesis of creatine, adrenaline and phosphatidylcholines

DNA methylation. Concept of methylation of foreign and medicinal compounds

Folic acid antivitamins. The mechanism of action of sulfonamide drugs.

Metabolism of phenylalanine and tyrosine. Phenylketonuria; biochemical defect, manifestation of the disease, methods of prevention, diagnosis and treatment.

Alkaptonuria and albinism: biochemical defects in which they develop. Impaired dopamine synthesis, parkinsonism

Decarboxylation of amino acids. Structure of biogenic amines (histamine, serotonin, γ-aminobutyric acid, catecholamines). Functions of biogenic amines

Deamination and hydroxylation of biogenic amines (as reactions of neutralization of these compounds)

Nucleic acids, chemical composition, structure. Primary structure of DNA and RNA, bonds that form the primary structure

Secondary and tertiary structure of DNA. Denaturation, renativation of DNA. Hybridization, species differences in the primary structure of DNA

RNA, chemical composition, levels of structural organization. Types of RNA, functions. The structure of the ribosome.

Structure of chromatin and chromosomes

Nucleic acid breakdown. Nucleases of the digestive tract and tissues. Breakdown of purine nucleotides.

Understanding the biosynthesis of purine nucleotides; initial stages of biosynthesis (from ribose-5-phosphate to 5-phosphoribosylamine)

Inosinic acid as a precursor of adenylic and guanylic acids.

Concept of the breakdown and biosynthesis of pyrimidine nucleotides

Nucleotide metabolism disorders. Gout; use of allopurinol for the treatment of gout. Xanthinuria. Orotaciduria

Biosynthesis of deoxyribonucleotides. The use of deoxyribonucleotide synthesis inhibitors for the treatment of malignant tumors

DNA synthesis and phases of cell division. The role of cyclins and cyclin-dependent proteinases in cell progression through the cell cycle

DNA damage and repair. Enzymes of the DNA repair complex

RNA biosynthesis. RNA polymerase. Concept of mosaic gene structure, primary transcript, post-transcriptional processing

Biological code, concepts, properties of the code, collinearity, termination signals.

The role of transfer RNAs in protein biosynthesis. Biosynthesis of aminoacyl-t-RNA. Substrate specificity of aminoacyl-tRNA synthetases.

The sequence of events on the ribosome during the assembly of a polypeptide chain. Functioning of polyribosomes. Post-translational processing of proteins

Adaptive gene regulation in pro- and eukaryotes. Operon theory. Functioning of operons

The concept of cell differentiation. Changes in the protein composition of cells during differentiation (using the example of the protein composition of hemoglobin polypeptide chains)

Molecular mechanisms of genetic variability. Molecular mutations: types, frequency, significance

Genetic heterogeneity. Polymorphism of proteins in the human population (variants of hemoglobin, glycosyltransferase, group-specific substances, etc.)

Biochemical basis of the occurrence and manifestation of hereditary diseases (diversity, distribution)

Basic systems of intercellular communication: endocrine, paracrine, autocrine regulation

The role of hormones in the metabolic regulation system. Target cells and cellular hormone receptors

Mechanisms of hormonal signal transmission into cells

Classification of hormones by chemical structure and biological functions

Structure, synthesis and metabolism of iodothyronines. Effect on metabolism. Changes in metabolism during hypo- and hyperthyroidism. Causes and manifestations of endemic goiter

Regulation of energy metabolism, the role of insulin and counter-insular hormones in ensuring homeostasis

Metabolic changes in diabetes mellitus. Pathogenesis of the main symptoms of diabetes mellitus

Pathogenesis of late complications of diabetes mellitus (macro- and microangiopathies, nephropathy, retinopathy, cataracts). Diabetic coma

Regulation of water-salt metabolism. Structure and functions of aldosterone and vasopressin

Renin-angiotensin-aldosterone system. Biochemical mechanisms of renal hypertension, edema, dehydration.

Oxygen toxicity: formation of reactive oxygen species (superoxide anion, hydrogen peroxide, hydroxyl radical)

Membrane damage due to lipid peroxidation. Mechanisms of protection against the toxic effects of oxygen: non-enzymatic (vitamins E, C, glutathione, etc.) and enzymatic (superoxide dismutase, catalase, glutathione peroxidase)

Biotransformation of medicinal substances. Effect of drugs on enzymes involved in the neutralization of xenobiotics

Fundamentals of chemical carcinogenesis. Introduction to some chemical carcinogens: polycyclic aromatic hydrocarbons, aromatic amines, dioxides, mitoxins, nitrosamines

Features of development, structure and metabolism of erythrocytes

Transport of oxygen and carbon dioxide by blood. Fetal hemoglobin (HbF) and its physiological significance

Polymorphic forms of human hemoglobins. Hemoglobinopathies. Anemic hypoxia

Heme biosynthesis and its regulation. Synthesis disorders topic. Porphyria

Heme breakdown. Neutralization of bilirubin. Disorders of bilirubin metabolism and jaundice: hemolytic, obstructive, hepatocellular. Jaundice of newborns

Diagnostic value of determining bilirubin and other bile pigments in blood and urine

Iron metabolism: absorption, blood transport, deposition. Iron metabolism disorders: iron deficiency anemia, hemochromatosis

The main protein fractions of blood plasma and their functions. The significance of their definition for the diagnosis of diseases. Enzymodiagnostics

Blood coagulation system. Stages of fibrin clot formation. Intrinsic and extrinsic coagulation pathways and their components

Principles of formation and sequence of functioning of enzyme complexes of the procoagulant pathway. The role of vitamin K in blood clotting

Basic mechanisms of fibrinolysis. Plasminogen activators as thrombolytic agents. Basic blood anticoagulants: antithrombin III, macroglobulin, anticonvertin. Hemophilia.

Clinical significance of biochemical blood test

The main cell membranes and their functions. General properties of membranes: fluidity, transverse asymmetry, selective permeability

Lipid composition of membranes (phospholipids, glycolipids, cholesterol). The role of lipids in the formation of lipid bilayer

Membrane proteins - integral, surface, “anchored”. The importance of post-translational modifications in the formation of functional membrane proteins

Mechanisms of substance transfer across membranes: simple diffusion, primary active transport (Na+-K+-ATPase, Ca2+-ATPase), passive symport and antiport, secondary active transport

Transmembrane signal transmission. Participation of membranes in the activation of intracellular regulatory systems - adenylate cyclase and inositol phosphate in hormonal signal transmission

Collagen: features of amino acid composition, primary and spatial structure. The role of ascorbic acid in the hydroxylation of proline and lysine

Features of collagen biosynthesis and maturation. Symptoms of vitamin C deficiency

Features of the structure and function of elastin

Glycosaminoglycans and proteoglycans. Structure and functions. The role of hyaluronic acid in the organization of the intercellular matrix

Adhesive proteins of the intercellular matrix: fibronectin and laminin, their structure and functions. The role of these proteins in cell-cell interactions and tumor development

Structural organization of the intercellular matrix. Changes in connective tissue during aging and collagenosis. The role of collagenase in wound healing. Oxyprolinuria

The most important proteins of myofibrils: myosin, actin, actomyosin, tropomyosin, troponin, actinin. Molecular structure of myofibrils

Biochemical mechanisms of muscle contraction and relaxation. The role of monovalent and calcium ion gradients in the regulation of muscle contraction and relaxation

Sarcoplasmic proteins: myoglobin, its structure and functions. Muscle extractives

Features of energy metabolism in muscles. Creatine phosphate

Biochemical changes in muscular dystrophies and muscle denervation. Creatinuria

Chemical composition of nervous tissue. Myelin membranes: features of composition and structure

Energy metabolism in nervous tissue. The importance of aerobic breakdown of glucose

Biochemistry of the origin and conduction of nerve impulses. Molecular mechanisms of synaptic transmission

Mediators: acetylcholine, catecholamines, serotonin, γ-aminobutyric acid, glutamic acid, glycine, histamine

Energy and resource saving

Solar collectors Calculation of a solar collector Determination of the area of ​​solar collectors. The main advantage of solar collectors is that the thermal energy they generate is free.

History of the 17th-19th centuries

Physical culture, sports and health improvement

Physical education in a health camp has specific features due to the relatively short period of stay in the camp, the diversity of the contingent of children by age, health status, level of physical development and physical fitness.

Marketing of industrial enterprises

The essence and functions of industrial enterprise marketing. Industrial products of the Chamber of Commerce and Industry. Marketing research on the market of industrial products of the Chamber of Commerce and Industry. Prices for new products.

Military strategy of Bohdan Khmelnytsky

The war was free for the Ukrainian people in the mid-17th century. formed a whole cohort of talented military leaders in Ukraine. Bogdan Khmelnitsky described the military-strategic meta, which included such basic directions. Battle of Pilyavtsy. Military campaign.

Hydrolyzing peptides and proteins, endopeptidase, and also drug.

Trypsin is a digestive enzyme

Trypsin is synthesized in the pancreas in the form of the proenzyme trypsinogen and, in this form, as part of pancreatic juice, enters the duodenum, where, in an alkaline environment, under the influence of the proteolytic enzyme enterokinase, the hexapeptide is removed from the trypsinogen molecule and the biologically active structure of trypsin is formed.

After activation of trypsin by enterokinase, the process of autocatalysis begins and trypsin then acts as an enzyme that activates trypsinogen, chymotrypsinogen, procarboxypeptidase, prophospholipase and other pancreatic enzymes.

In the blood of healthy patients, the average trypsin content is 169 ± 17.6 ng/ml. The range of fluctuations (in children) is from 98.2 to 229.6 ng/ml.

Trypsin - medicine

• "B06 Other hematological preparations", code "B06AA07 Trypsin"
• "D03 Preparations for the treatment of wounds and ulcers", code "D03BA01 Trypsin"
• "M09 Other drugs for the treatment of diseases of the musculoskeletal system", "M09AB52 Trypsin in combination with other drugs."

Indications for the use of crystalline trypsin

Trypsin is a component of combination drugs

Trypsin is also used as part of combined enzyme, immunomodulatory and other drugs. In particular, trypsin is included in Wobenzym, Phlogenzyme, Himopsin.

Trypsin has contraindications, side effects and application features; consultation with a specialist is necessary.

Russian name

Latin name of the substance Trypsin

Pharmacological group of the substance Trypsin

Nosological classification (ICD-10)

CAS code

Characteristics of the substance Trypsin

Endogenous proteolytic enzyme of the hydrolase class, catalyzes the breakdown, incl.

proteins, peptones, low molecular weight peptides through bonds in the formation of which the carboxyl groups of L-arginine and L-lysine take part. Trypsin is a protein with a relative molecular weight of 21,000, produced and secreted by the mammalian pancreas as inactive trypsinogen, which is then converted to trypsin by the enzyme enteropeptidase in the duodenum.

Trypsin is obtained from the pancreas of cattle followed by lyophilization. In medical practice, crystalline trypsin (approved for both local and parenteral use) and amorphous trypsin (only for local use) are used.

Crystalline trypsin is a white or white powder with a slightly yellowish tint, odorless, or a porous mass (after lyophilization). Easily soluble in water, isotonic sodium chloride solution; solutions are easily destroyed in neutral and alkaline environments.

Pharmacology

When applied locally, it has anti-inflammatory, anti-burn, regenerating and necrolytic effects. Breaks down necrotic tissue and fibrinous formations, thins viscous secretions, exudates, blood clots. The enzyme is active at pH 5.0-8.0 with optimum action at pH 7.0. In relation to healthy tissues, it is inactive and safe due to the presence of trypsin inhibitors - specific and nonspecific.

Immobilized crystalline trypsin promotes the rejection of necrotic tissue, dilutes pus and facilitates its evacuation, and improves the process of wound regeneration. Unlike non-immobilized crystalline trypsin, it does not cause changes in the hemostatic system.

In inflammatory diseases of the respiratory tract, trypsin thins and facilitates the removal of viscous secretions and exudates with sputum. In these cases, it is used for inhalation and intramuscular injection. For exudative pleurisy and pleural empyema, it can be administered intrapleurally. In case of tuberculous empyema, caution should be exercised due to the fact that resorption of exudate in some cases may contribute to the development of bronchopleural fistula.

The anti-inflammatory effect determines the use of crystalline trypsin intramuscularly for thrombophlebitis (trypsin does not replace anticoagulants), inflammatory-dystrophic forms of periodontal disease, etc.

For eye diseases, it is used intramuscularly and locally (in the form of eye drops and baths).

Trypsin is used topically to treat burns, bedsores, and purulent wounds.

In dentistry, it is used for ulcerative-necrotic diseases of the oral mucosa, periodontal diseases, periodontitis, odontogenic sinusitis, etc.

Use of the substance Trypsin

Respiratory tract diseases (including tracheitis, bronchitis, bronchiectasis, pneumonia, postoperative pulmonary atelectasis, pleural empyema, exudative pleurisy), thrombophlebitis, periodontal disease (inflammatory-dystrophic forms), osteomyelitis, sinusitis, otitis media, iritis, iridocyclitis, hemorrhage in the anterior chamber of the eye, swelling of the periorbital area after operations and injuries, burns, bedsores; purulent wounds (locally).

Contraindications

For injection- cardiac decompensation, pulmonary emphysema with respiratory failure, decompensated forms of pulmonary tuberculosis, liver dystrophy, liver cirrhosis, infectious hepatitis, pancreatitis, hemorrhagic diathesis. Do not inject into bleeding cavities, intravenously, or apply to ulcerated surfaces of malignant tumors.