Resistance (from lat. resister - resist, resist) - the body’s resistance to the action of extreme stimuli, the ability to resist without significant changes in the constancy of the internal environment; this is the most important qualitative indicator of reactivity;
Nonspecific resistance represents the body’s resistance to damage (G. Selye, 1961), not to any individual damaging agent or group of agents, but in general to damage, to various factors, including extreme ones.
It can be congenital (primary) and acquired (secondary), passive and active.
Congenital (passive) resistance is determined by the anatomical and physiological characteristics of the organism (for example, the resistance of insects, turtles, due to their dense chitinous cover).
Acquired passive resistance occurs, in particular, with serotherapy and replacement blood transfusion.
Active nonspecific resistance is determined by protective-adaptive mechanisms and arises as a result of adaptation (adaptation to the environment), training to a damaging factor (for example, increased resistance to hypoxia due to acclimatization to a high-mountain climate).
Nonspecific resistance is provided by biological barriers: external (skin, mucous membranes, respiratory organs, digestive apparatus, liver, etc.) and internal - histohematic (blood-brain, hemato-ophthalmic, hematolabyrinthine, hematotesticular). These barriers, as well as biologically active substances contained in fluids (complement, lysozyme, opsonins, properdin) perform protective and regulatory functions, maintain the optimal composition of the nutrient medium for the organ, and help maintain homeostasis.
FACTORS REducing NON-SPECIFIC RESISTANCE OF THE ORGANISM. WAYS AND METHODS OF ITS INCREASE AND STRENGTHENING
Any impact that changes the functional state of regulatory systems (nervous, endocrine, immune) or executive (cardiovascular, digestive, etc.) leads to a change in the reactivity and resistance of the body.
Factors that reduce nonspecific resistance are known: mental trauma, negative emotions, functional inferiority of the endocrine system, physical and mental fatigue, overtraining, fasting (especially protein), malnutrition, lack of vitamins, obesity, chronic alcoholism, drug addiction, hypothermia, colds, overheating, painful injury, detraining of the body and its individual systems; physical inactivity, sudden changes in weather, prolonged exposure to direct sunlight, ionizing radiation, intoxication, previous diseases, etc.
There are two groups of pathways and methods that increase nonspecific resistance.
With a decrease in vital activity, loss of the ability to exist independently (tolerance)
2. Hypothermia
3. Ganglioblockers
4. Hibernation
When maintaining or increasing the level of vital activity (SNPS - a state of non-specifically increased resistance)
1 1. Training of basic functional systems:
Physical training
Hardening to low temperatures
Hypoxic training (adaptation to hypoxia)
2 2. Changing the function of regulatory systems:
Autogenic training
Verbal suggestion
Reflexology (acupuncture, etc.)
3 3. Non-specific therapy:
Balneotherapy, spa therapy
Autohemotherapy
Protein therapy
Nonspecific vaccination
Pharmacological agents (adaptogens - ginseng, Eleutherococcus, etc.; phytocides, interferon)
To the first group These include impacts through which resilience is increased due to the body’s loss of the ability to exist independently and a decrease in the activity of vital processes. These are anesthesia, hypothermia, hibernation.
When an animal in hibernation is infected with plague, tuberculosis, or anthrax, the diseases do not develop (they occur only after it awakens). In addition, resistance to radiation exposure, hypoxia, hypercapnia, infections, and poisoning increases.
Anesthesia increases resistance to oxygen starvation and electric current. In a state of anesthesia, streptococcal sepsis and inflammation do not develop.
With hypothermia, tetanus and dysentery intoxication are weakened, sensitivity to all types of oxygen starvation and to ionizing radiation is reduced; increased resistance to cell damage; allergic reactions are weakened, and in the experiment the growth of malignant tumors is slowed down.
In all these conditions, there is a deep inhibition of the nervous system and, as a consequence, of all vital functions: the activity of regulatory systems (nervous and endocrine) is inhibited, metabolic processes are reduced, chemical reactions are inhibited, the need for oxygen is reduced, blood and lymph circulation slows down, and the temperature drops body, the body switches to a more ancient metabolic pathway - glycolysis. As a result of the suppression of normal life processes, active defense mechanisms are switched off (or inhibited), and a non-reactive state arises, which ensures the body’s survival even in very difficult conditions. At the same time, he does not resist, but only passively tolerates the pathogenic effect of the environment, almost without reacting to it. This condition is called tolerability(increased passive resistance) and is a way for the body to survive in unfavorable conditions, when it is impossible to actively defend itself and avoid the action of an extreme irritant.
To the second group The following methods of increasing resistance while maintaining or increasing the level of vital activity of the body include:
Adaptogens are agents that accelerate adaptation to adverse effects and normalize disorders caused by stress. They have a broad therapeutic effect, increase resistance to a number of factors of a physical, chemical, biological nature. The mechanism of their action is associated, in particular, with their stimulation of the synthesis of nucleic acids and proteins, as well as with the stabilization of biological membranes.
By using adaptogens (and some other medications) and adapting the body to the action of unfavorable environmental factors, it is possible to create a special condition nonspecifically increased resistance - SNPS. It is characterized by an increase in the level of vital activity, mobilization of active defense mechanisms and functional reserves of the body, and increased resistance to the action of many damaging agents. An important condition for the development of SNPS is a dosed increase in the force of exposure to unfavorable environmental factors, physical activity, and the elimination of overloads, in order to avoid disruption of adaptation-compensatory mechanisms.
Thus, the organism that is more resistant is the one that resists better, more actively (SNPS) or is less sensitive and has greater tolerance.
Managing the reactivity and resistance of the body is a promising area of modern preventive and therapeutic medicine. Increasing nonspecific resistance is an effective way to generally strengthen the body.
The invention relates to medicine, in particular to the therapeutic correction of functional abnormalities, characterized as a decrease in the body’s resistance. The method allows to increase the effectiveness of therapeutic effects. To do this, varying subtherapeutic doses of biostimulants of plant origin are administered daily. In this case, the daily dose is determined according to the law of random numbers from the range of their variations, each of which differs in the amount of the drug contained in one drop of tincture, while for men under 65 years of age variations are used, starting from the lower subtherapeutic dose; for men over 65 years of age and for women of any age, variations are selected, starting with a dose 1.5 times less than the subtherapeutic one; for children aged 1 to 4 years - start from 1/10, from 4 to 6 years - from 1/5, from 6 to 19 years - from 1/4, from 10 to 14 years - from 1/3, from 14 up to 16 years - with 1/2 subtherapeutic dose and in a satisfactory state of the body, variations of 16 doses are used, in a weakened state - from 8 doses, and in a sharply weakened state - from 4 doses. 2 z. items f-ly, 2 tables.
The invention relates to medicine, in particular to the therapeutic correction of functional abnormalities, characterized as a decrease in the body’s resistance, and can be used for prevention, healing and increasing the body’s resistance under various stresses and diseases. There is a known method of increasing the body's resistance by taking various biostimulants, for example, Eleutherococcus, ginseng, etc. (Brechman N.N. Man and biological active substances. L. 1976; Dardymov I.V. Ginseng, Eleutherococcus." M. Nauka, 1976). However, the known method does not take into account gender and age. Taking biostimulants, which are xenobiotics, in relatively large doses leads to a breakdown in stress, especially in weakened individuals. There is a known method of increasing the body's resistance (in the book "Adaptation reactions and body resistance" Garkavi L. Kh. Kvakina E. B. Ukolova M. A. 1990, Rostov-on-Don, p. 45), including the development of an activation reaction through a correctly selected dose of a biostimulant and its systematic change (influence strength) towards an increase or reduction. However, this method has certain disadvantages: the selection of doses is carried out cybernetically according to the signal indicator of the reaction - the percentage of lymphocytes in the leukocyte formula. Therefore, the previously proposed method requires frequent blood tests, which complicates its mass use. In addition, the blood test takes time, the required dose change is delayed, which reduces the effectiveness of the method. The purpose of the invention is to increase the effectiveness of therapeutic effects to increase the body's resistance, resistance to damaging influences and diseases. The goal is achieved by daily administering changing subtherapeutic doses of biostimulants to patients, using a tincture of biostimulants of plant origin, the daily dose is determined by the law of random numbers from the range of their variations, each of which differs in the amount of the drug contained in one drop of tincture. Moreover, for men under 65 years of age use variations ranging from the lower subtherapeutic dose; for men over 65 years of age and for women of any age, variations are selected starting with a dose 1.5 times less than the subtherapeutic one; for children aged 1 to 4 years - start from 1/10, from 4 to 6 years from 1/5, from 6 to 10 years from 1/4, from 10 to 14 years 1/3, from 14 to 16 years with 1/2 subtherapeutic dose and in a satisfactory state of the body, variations of 16 doses are used, in a weakened state of 8 doses, and in a sharply weakened state of 4 doses; treatment is continued for a month. A fourfold, threefold, or twofold coin toss is used as a random number generator; for each value of the resulting combinations a certain dose of the biostimulant is recorded. To prepare doses less than one drop, use an extract diluted 10 times with water. The invention is new, since it is not known from the level of medicine in the field of therapeutic correction of functional abnormalities, characterized by a decrease in the body's resistance. The proposed method differs from the known ones in that the individual subtherapeutic dose of the stimulant used daily is determined according to the law of random numbers and is made dependent on gender and age. A random number generator is used with a uniform distribution of four and three or two coin tosses, each value of which is assigned a certain subtherapeutic dose of the stimulant. Thus, the proposed method of increasing the body’s resistance differs significantly from the known one and meets the “novelty” criterion of the invention. The invention has an inventive step, since for a specialist (a doctor of any specialty) it does not clearly follow from the level of development of medicine in the field of increasing the body's resistance under various stresses and diseases and for prevention. The advisability of changing the dosage according to the law of random numbers is explained by the need to maintain the information value of stimulation, i.e., the need to maintain the “novelty” factor during the course of exposure. Novelty is reduced due to the development of an “expectation reaction”: when a dose is administered daily according to a known scheme (in a previously known way), the body is, as it were, warned about the dose size. The factor of “novelty” leads to the predominance of the process of excitation in the brain, and since the stimulus is small (subtherapeutic doses), the excitation that develops is not excessive, but moderate, physiological. The validity of this approach is also confirmed by many years of experimental research (Garkavi L. Kh. Kvakina E. B. Ukolova M. A. 1990). It is precisely this nature of changes in the central nervous system, as was shown earlier, that is observed during the development of the activation reaction, which most significantly reduces the body’s resistance (Garkavi L. Kh. 1969; Kvakina E. B. 1972; Garkavi L. Kh. Kvakina E. B. Ukolova M A. 1979). The use of the law of random numbers to set the daily dose causes randomness in changing doses, which prevents the development of addiction and helps maintain the “novelty factor”. Thus, the proposed technical solution is not obvious, since it does not follow from the level of development in this field of medicine, and is not known either in the world or in the Russian (CIS) medical literature. The invention is industrially applicable, since the technical result achieved with its use of increasing the body's resistance, contributing to an increase in the level of health, prevention of various diseases, their easier course, greater effectiveness of treatment allow us to consider the method industrially applicable in various fields of medicine: for prevention, improvement, relief course of the disease. The advisability of taking into account gender and age is associated with the great sensitivity of the female body and the increase in sensitivity with aging. Let us consider the choice of dose according to the law of random numbers (Monte Carlo method) using the example of Eleutherococcus, a single therapeutic dose of which is 30–25 drops of extract. Starting with a maximum subtherapeutic dose, for example, 24 drops for men under the age of 65, for example, 16 lower doses are prescribed with an interval of 1 drop (this interval is taken for ease of practical use). Each dose is numbered by a serial number, starting with N 1. Thus, each serial number corresponds to its own dose (Table 1). For women of any age and men over 65 years of age, the maximum subtherapeutic dose is taken 1.5 times less than for men under 65 years of age. Then the dose is prescribed while maintaining an interval of 1 drop. For doses smaller than a drop, an extract diluted with water 10 times (E/10) is used. To select the daily dose using the Monte Carlo method, a “random number generator” with uniform distribution is used. Such a generator can be: a machine for obtaining random numbers, a table of random numbers, or a coin toss available to everyone. When tossing a coin, there are two possible results: heads (O) or tails (P). To ensure the necessary randomness of dose distribution, throwing the moments three times is sufficient, which gives 8 possible combinations of 3. Each of the 8 combinations is associated with one of the 8 selected subtherapeutic doses. Tossing a coin four times provides even greater chaos, as it gives 16 dose options (Table 1), and tossing a coin twice less, since it gives 4 dose options. In elderly and weakened people, you should start with tossing a coin 3 times and using 8 minimum doses for a given gender and age of dose values, and in especially severe cases - even with 2 times tossing a coin and using four minimum doses. Considering the circadian rhythm of the “activation reaction” caused, the biostimulant should be taken once a day, preferably from 7 to 9 o’clock, when informational influence is sufficient to form the said reaction. Before each dose of a biostimulant (daily, on an empty stomach, 1 time per day), it is necessary, by tossing a coin 2, 3 or 4 times, to record the sequence of “heads” and “tails” that fall out and then determine the value of the corresponding dose according to Table 1. The criterion for selecting doses is their individualization depending on age and gender, evaluation of effectiveness - all this is based on the theory and practice of adaptive reactions that we have been developing for many years. Highly informative and well correlated with changes in the neuroendocrine and immune systems, a signal indicator of the reaction, a specially calculated leukocyte formula and the total number of leukocytes, is an important criterion both for the state of the body and for assessing the effectiveness and correctness of the selected doses. The percentage of lymphocytes determines the type of reaction (training, activation, stress), and deviations from the norm in the percentage of other elements of the blood count (eosinophils, basophils, rod neutrophils, monocytes) and the total number of leukocytes (leukopenia or leukocytosis) indicate the presence of tension, non-physiological activation or training reactions. This indicator and a change in well-being, a decrease or disappearance of complaints, and in the presence of objectively determined signs of disorders, their normalization (for example, blood pressure), a decrease in the number of pathogenic colonies in the autoflora of the skin together allow us to judge the effectiveness of the effects. It should be noted that the listed signs in the vast majority of cases (at least 90) correlate well. The fact that in the selected prototype doses of a biostimulant “can lead to the development of stress” is proven simply: the parameters of the leukocyte formula become characteristic of stress, as the author of stress G. Salye found. The fact that “taking the same doses” leads to the development of an expectation reaction, which reduces the therapeutic effectiveness of the biostimulant, is due to the fact that under any strict regime of variation in the dose (strength) of the active factor, the body is capable of extrapolation. Specifically, this is manifested by the fact that after the first change in the nature of the reaction (can last from 2 days to a week), in the case of taking the same dose or changing the dose according to a rigid scheme, a return to the original state occurs (according to blood parameters), which is associated with return to the original state of health, i.e. e. the therapeutic effectiveness of the biostimulator is reduced or removed. The activation reaction was judged by the percentage of lymphocytes in the leukocyte formula. In some people (25 people in each group), the development of the activation reaction was also judged by the autoflora of the skin. According to the proposed method, this was carried out not to select a dose, but to control (evidence) the development of the activation reaction before the start of exposure and at the end of exposure, which lasted for a month. The choice of a known or proposed method for obtaining an activation reaction was carried out on the basis of randomization: even dates of the start of influences - a known method, odd ones - a proposed one. The results of a comparison of the prototype and the proposed method showed that the proposed method effectively increases resistance in people with reduced resistance (in prenosological conditions) and causes the development of an activation reaction in a significantly higher percentage of cases. A high percentage of lymphocytes, a high number of pathogenic colonies in the autoflora of the skin, the disappearance of persistent complaints, an improvement in general condition and an increase in performance indicate the usefulness of the developing activation reaction (Table 2). As an example of a specific implementation of the proposed method, we present the following extracts from outpatient records. 1. Card No. 3. A 46-year-old woman, upon treatment, subjective complaints of headaches, poor sleep, decreased performance, fatigue, depressed mood. Objectively: the percentage of lymphocytes in the leukocyte formula is 18.5, which corresponds to a stress reaction, the number of pathogenic colonies of skin autoflora is 42, which is also characteristic of stress. The patient underwent a medical examination and no specific disease was identified. Purpose: Eleutherococcus in a dose of 16 to 1 drop. Each day's dose was selected by tossing a coin four times and then determined according to the accompanying table. 1. In this case, for example, as a result of daily tossing a coin, we received: Day Number of drops First OROR 10 Second RROO 3 Third RRRO -1 Fourth ORRO 9 Fifth OOOR 14 Sixth ROOR 6 Seventh RRRR 15
Eighth RRRO 1
Ninth ORRO 9
Tenth ROOR 6
Eleventh OORR -12
Twelfth OOOR 14
Thirteenth OROO 11
Fourteenth RROO 3
Fifteenth OORR 12
Sixteenth OORO 13
Seventeenth ROOR 6
Eighteenth ORRR 8
Nineteenth PORR 4
Twentieth RROR 2
Twenty-first OORO 13
After 3 weeks of daily use of eleutherococcus in the indicated doses, there is a subjective improvement in the condition, disappearance of complaints, and increased performance. The percentage of lymphocytes in the leukocyte formula became 35, which corresponds to an activation reaction, the number of pathogenic skin colonies in the autoflora decreased to three, which is also characteristic of an activation reaction. 2. Map No. 15
A 52-year-old man presented with subjective complaints of pain in the heart area, headaches, general weakness, poor sleep, irritability, feelings of fear and anxiety, self-doubt, impotence, decreased performance. Objectively: the number of lymphocytes in the leukocyte formula is 17, which corresponds to stress, the number of pathogenic colonies in the autoflora of the skin is 40, which is also characteristic of stress. Treatment was carried out with an alcoholic extract of pantocrine for 21 days at a dose of 20 to 5 drops. The choice of the daily dose was carried out according to the law of random numbers by tossing a coin four times in accordance with the table. 1:
Day Number of drops
First OOOR 20
Second RROO 13
Third ROOR 11
Fourth RRRO 8
Fifth RORO 9
Sixth ORRR 5
Seventh PORR 6
Eighth RRRR 19
Ninth OOOR 18
Tenth OROR 10
Eleventh ORRO -12
Twelfth OOOR 18
Thirteenth ORRO 12
Fourteenth RROO 13
Fifteenth RORR 11
Sixteenth RRRR 19
Seventeenth ORR 14
Eighteenth OROR 10
Nineteenth RROR 7
Twentieth OORR 14
Twenty-first ROOO 15
After three weeks, persistent complaints disappeared, performance increased, sexual potency increased, and mood improved. Objectively: blood pressure
125/30, the number of lymphocytes in the leukocyte formula is 33, which corresponds to an activation reaction, the number of pathogenic colonies in the autoflora has decreased to 5, which is also characteristic of activation. 3. Map N 37
A man aged 32 years. When presenting, there are subjective complaints of pain in the epigastric region that occurs immediately after eating, a feeling of heaviness in this area, belching of air, poor sleep, decreased performance, fatigue, and lethargy. He was treated for a long time and continues to be treated for hypoacid gastritis without lasting effect. Objectively: the number of lymphocytes in the leukocyte formula is 15, the number of colonies of pathogenic microbes is 48, which is typical (both lymphocytes and autoflora) for a stress reaction. Treatment with liquid Leuzea extract was prescribed in a dose of 19 to 4 drops. Choosing a daily dose according to the law of random numbers using a coin toss:
Day Number of drops
First ROOR 10
Second OOOR 17
Third ROOR 10
Fourth RRRR 18
Fifth OORO 16
Sixth OOOR 17
Seventh OOOR 17
Seventh RROO 12
Eighth OOOR 17
Ninth OOO 19
Tenth ORRR 3
Eleventh OORO -16
Twelfth ORRO 11
Thirteenth RRRO 7
Fourteenth OORO 16
Fifteenth OROO -15
Sixteenth RROO 12
Seventeenth ORRR 3
Eighteenth ROOR 10
Nineteenth RRRO 7
Twentieth RRRR 18
Twenty-first OROO 11
Twenty-second ROOO 14
Twenty-third RROO 12
Twenty-fourth RRRO 7
Twenty-fifth ORRO 11
Twenty-sixth RRRO 7
Twenty-seventh JSC 16
Twenty-eighth LLC 19
After 28 days, persistent complaints disappeared, only sometimes a vague feeling of discomfort in the epigastric region appears, performance increased, sleep and appetite, and mood improved. The percentage of lymphocytes in the leukocyte formula is 40; pathogenic colonies in the autoflora are single, which is characteristic of an activation reaction. Map N 7
Woman aged 49 years. Upon treatment, complaints of pain in the heart area, interruptions, weakness, fatigue, poor sleep. Objectively: blood pressure is 80/65. The ECG shows right ventricular extrasystole. The number of lymphocytes in the leukocyte formula is 25, which corresponds to the training response, the number of pathogenic colonies is 9. An alcoholic tincture of ginseng root was prescribed for 28 days in a dose range from 7 drops of undiluted tincture to 1 drop of tincture diluted 10 times with water. To select the daily dose, a coin toss was used four times, the dosage was carried out in accordance with the table. 1:
Day -
First OORR 1
Second OOOR 5
Third ORRR 1 solution 1/10
Fourth OROO 3
Fifth RRRO 4
Sixth PORR 5 size 1/10
Seventh ROOO 2
Eighth OOO 7
Ninth ROOO 2
Tenth RORO 5 solution 1/100
Eleventh RRRO 4 sizes 1/10
Twelfth RRRR 6
Thirteenth RROO 9
Fourteenth OOO 7
Fifteenth RRRO 4 sizes 1/10
Sixteenth OORO 4
Seventeenth RRRR 6
Eighteenth RRRO 4 sizes 1/10
Nineteenth RROR 3 sizes 1/10
20th OORR 1
Twenty-first OOOR 5
Twenty-second ROOR 7 solution 1/10
Twenty-third RORO 5 solution 1/10
Twenty-fourth RRRR 6
Twenty-fifth OROR 6 solution 1/10
Twenty-sixth RRRO 4 solutions 1/10
Twenty-seventh ROOO 2
Twenty-eighth RORO 5 solution 1/10
After 3 weeks, the complaints disappeared, extrasystole was not detected on the ECG, blood pressure was 115/70, the number of lymphocytes in the leukocyte formula was 43, which corresponds to an activation reaction, and there was no pathogenic flora. Card N 10
A man aged 65 years. Upon treatment, complaints of weakness, dizziness, pain in the heart, poor sleep, memory impairment. Objectively: blood pressure is 145/90, the number of lymphocytes in the leukocyte formula is 18, the number of pathogenic colonies in the skin autoflora is 64, which corresponds to stress. Treatment was carried out with golden root extract (Rhodiola rosea), in a dose of 9 drops of undiluted extract to 3 drops of extract diluted 10 times with water for a month. The choice of daily dose was carried out by tossing a coin four times and was determined in accordance with a table constructed on the same principle as the table. 1 for Eleutherococcus. In this case:
Day Quantity
First RROO 2
Second OORR 3
Third OOO 8
Fourth ORO 6
Fifth PORR 4 solutions 1/10
Sixth OROO 5
Seventh RORR 7 solution 1/10
Eighth ROOR 9
Ninth RRRR 8
Tenth OOO 9
Eleventh RROO 2
Twelfth ORRO 1
Thirteenth ROOO 4
Fourteenth OROO 5
Fifteenth OROO 5
Sixteenth RRRO 6 solutions 1/10
Seventeenth OORO 6
Eighteenth RRRO 6 sizes 1/10
Nineteenth OROO 5
20th ORRO 1
Twenty-first OROO 5
Twenty-second OORR 3
Twenty-third RROO 2
Twenty-fourth OOOR 7
Twenty-fifth RROO 2
Twenty-sixth OROO 5
Twenty-seventh ROOR 9 solution 1/10
Twenty-eighth RORR 4 solutions 1/10
After treatment, the patient felt a surge of strength, noted improvement in memory and mood; The heart pain and dizziness disappeared. Blood pressure is 125/80, the number of lymphocytes is 33, the number of pathogenic colonies in the skin autoflora is 7, which corresponds to an activation reaction. In order to increase the body's resistance, the method was tested on male and female high school students every day for 15 days. The daily dose was determined by the proposed method of increasing the body's resistance according to the law of random numbers, which caused the activation reaction to be called. A four-fold coin toss was used as a random number generator, for each value of which (the sequence of four combinations of “heads” and “tails”) a certain dose of the biostimulant was recorded. The subjects were divided into 2 groups. The first group received exposure with dose selection according to the law of random numbers, and the second group received the same dose 2 times a day as standard. A total of 166 people were tested to prevent colds. of these, 116 using the proposed method, 50 using the prototype. After carrying out preventive treatment during the autumn-winter period for 4 months of colds in the first group (exposure according to the proposed method), there were 14 out of 116 people. (12), from the prototype group of 50, 10 people fell ill. (20). Thus, the use of biostimulants in the dosage selection mode according to the law of random numbers makes it possible to increase the body's resistance to a greater extent than in the prototype group when using a standard mode of exposure. The technical and economic efficiency of the proposed method of increasing the body's resistance lies in the fact that the use of the method allows one to increase the body's resistance to external influences and morbidity. In addition, the method is effective for carrying out preventive and health-improving work among mass populations, since it is simple, accessible and does not require large material costs or time.
Resistance (from lat. resister - resist, resist) - the body’s resistance to the action of extreme stimuli, the ability to resist without significant changes in the constancy of the internal environment; this is the most important qualitative indicator of reactivity;
Nonspecific resistance represents the body’s resistance to damage (G. Selye, 1961), not to any individual damaging agent or group of agents, but in general to damage, to various factors, including extreme ones.
It can be congenital (primary) and acquired (secondary), passive and active.
Congenital (passive) resistance is determined by the anatomical and physiological characteristics of the organism (for example, the resistance of insects, turtles, due to their dense chitinous cover).
Acquired passive resistance occurs, in particular, with serotherapy and replacement blood transfusion.
Active nonspecific resistance is determined by protective-adaptive mechanisms and occurs as a result of adaptation (adaptation to the environment), training to a damaging factor (for example, increased resistance to hypoxia due to acclimatization to a high-mountain climate).
Nonspecific resistance is provided by biological barriers: external (skin, mucous membranes, respiratory organs, digestive apparatus, liver, etc.) and internal - histohematic (blood-brain, hemato-ophthalmic, hematolabyrinthine, hematotesticular). These barriers, as well as biologically active substances contained in fluids (complement, lysozyme, opsonins, properdin) perform protective and regulatory functions, maintain the optimal composition of the nutrient medium for the organ, and help maintain homeostasis.
The body's resistance is closely related to the functional state and reactivity of the body. It is known that during hibernation, some animal species are more resistant to the effects of microbial agents, for example, to tetanus and dysentery toxins, pathogens of tuberculosis, plague, glanders, and anthrax. Chronic fasting, severe physical fatigue, mental trauma, poisoning, colds, etc. reduce the body's resistance and are factors predisposing to the disease.
There are nonspecific and specific resistance of the organism. Nonspecific resistance of the body is ensured by barrier functions, the content of special biologically active substances in body fluids - complements, lysozyme, opsonins, properdin, as well as the state of such a powerful nonspecific defense factor as phagocytosis. Adaptation syndrome plays an important role in the mechanisms of nonspecific resistance of the body. The specific resistance of an organism is determined by the species, group or individual characteristics of the organism under special influences on it, for example, during active and passive immunization against pathogens of infectious diseases.
It is practically important that the body’s resistance can be enhanced artificially with the help of specific immunization, as well. also by administering convalescent serums or gamma globulin. Increasing the body's nonspecific resistance has been used in traditional medicine since ancient times (cauterization and acupuncture, creating foci of artificial inflammation, using plant substances such as ginseng, etc.). In modern medicine, such methods of increasing the body's nonspecific resistance as autohemotherapy, protein therapy, and the introduction of antireticular cytotoxic serum have taken a strong place. Stimulating the body's resistance with the help of nonspecific influences is an effective way to generally strengthen the body, increasing its protective capabilities in the fight against various pathogens.
The invention relates to medicine and can be used in cases where it is necessary to increase the body’s resistance to infection in cancer and autoimmune diseases, to accelerate the restoration of the normal functioning of organs and tissues damaged as a result of the side effects of drugs, to increase resistance to toxic substances. The essence of the invention is that ascorbigen is prescribed at a dose of 10 mg/kg for 5-30 days. The method ensures an increase in nonspecific resistance to infectious and toxic agents, reduces the risk of developing a serious disease and speeds up the recovery of patients. 3 salary f-ly, 1 table., 2 ill.
The invention relates to medicine and can be used in all cases where it is necessary to increase the body's resistance: to prevent infections and treat patients suffering from infectious and inflammatory diseases; for chemoprophylaxis of carcinogenesis and therapy of cancer patients, to improve the results of therapy for patients suffering from autoimmune diseases; to accelerate the restoration of normal functioning of organs and tissues (hematopoiesis, immunoreactivity, gastrointestinal tract, hair) damaged as a result of side effects of drugs; to increase resistance to toxic substances.
It is known that currently the resistance of many people to infections, cancer and toxic substances is reduced. Specific methods of increasing the body's resistance, such as vaccination, are often not effective. Therefore, an urgent task is to search for drugs that nonspecifically increase the body’s resistance or potentiate the effect of specific stimulants. The results of treatment of many patients suffering from infectious and oncological diseases with the help of available means are often unsatisfactory, in particular due to resistance to drugs and the body’s defenses of pathogenic microorganisms and tumor cells, which have a different nature and intensity (congenital, acquired, partial, complete, to one, several or all existing drugs). In this regard, the urgent task is to develop drugs that potentiate the effect of existing drugs, helping the latter to demonstrate their activity.
Finally, when using almost all anti-infective and especially anti-tumor drugs, side effects of varying severity can develop. Thus, the side effects of antitumor cytostatics make up the largest portion of all iatrogenic diseases. For example, the effective cytostatic CYCLOPHOSPHAMIDE, widely used alone and in combination with other drugs and radiation to treat patients suffering from cancer, autoimmune and inflammatory diseases, often causes neutropenia, immunosuppression, damage to the mucous membrane of the gastrointestinal tract and baldness. As a result, anti-infective resistance decreases and the risk of developing infectious complications sharply increases, often as a result of the penetration of pathogenic microorganisms from the intestinal lumen into the blood. Currently, there are no effective drugs for the prevention and treatment of damage to the mucous membrane of the gastrointestinal tract (mucositis) caused by radiochemotherapy. The development of such drugs is necessary to improve the results and safety of treatment with cytostatics.
There is a known method of increasing the nonspecific resistance of the body by introducing OLEXIN. This preparation is a purified aqueous extract of peach leaves. Its activity is associated with substances with a phenolic structure, in particular flavonoids (Dobritsa V.P. et al. 2001). The disadvantage of this method is that individual intolerance often develops. There is no information about its effects on toxic alopecia and intestinal immune cells. The pharmacokinetics of OLEXIN cannot be fully characterized, and the effect on the immunological status may lead to unexpected effects.
The essence of the invention is that ascorbigen is prescribed at a dose of 10 mg/kg for 5-30 days.
Ascorbigen is one of the most important compounds formed during the processing of cruciferous plants. The Cruciferous family includes all types of cabbage, Brussels sprouts, cauliflower, broccoli, turnips, rutabaga, radishes and other vegetables. Plants of this family are intensively used in human nutrition. Epidemiological and experimental data, in particular, indicate that a lack of these vegetables in food contributes to the development of diseases, in particular some types of cancer, and the presence in sufficient quantities, on the contrary, provides anticarcinogenic properties.
Ascorbigen, 2-C-(indol-3-yl)methyl--L-xylo-hex-3-ulofuranosono-1,4-lactone is obtained synthetically from L-ascorbic acid and indolyl-3-carbinol. This is an individual optically active compound (Mukhanov V.I. et al., 1984). According to NMR, HPLC and TLC data, the synthetic product is completely identical to the natural one.
The essential features of the proposal are the mode and parameters of the method. Special studies have shown that increasing the dose leads to a toxic effect, and decreasing the dose leads to a decrease in the declared effect. Shortening the time of administration of the drug reduces the effectiveness of the effect, and lengthening the time of administration does not lead to increased effectiveness.
Below are the research results confirming the advantages of the claimed method.
1. The effect of ascorbigen on Paneth cells involved in the formation of innate immunity and the protective function of the small intestinal mucosa.
Materials and methods:
The study was conducted on 30 C 57 B1 mice and 20 F 1 hybrid mice (CBAxC 57 B1) males weighing 20-22 grams.
Animals received ascorbigen in single doses from 10 to 1000 mg/kg per stomach for 14 days. At the end of the course of administration, the animals were killed. Sections of the small intestine were fixed in a 10% solution of neutral formalin, embedded in paraffin according to the standard procedure, and short series of sections were stained with hematoxylin-eosin.
Results:
On the first day after the 14-fold administration of the drug, a sharp increase in the number of Paneth cells was found in the mucous membrane of the small intestine. In some glands, they were located not only in the area of the bottom of the gland, but also filled the entire crypt right up to the neck of the gland. If normally the ratio of Paneth cells and cambial elements of the cylindrical epithelium is 1:1, then with the use of ascorbigen it increases to 2:1.
The number of eosinophilic granules in Paneth cells and their size also increased sharply. The lumen of the gland crypt was expanded and filled with granules released from Paneth cells by endocytosis.
2. The influence of ascorbigen on the processes of repair of damage to the mucous membrane of the small intestine caused by the administration of CYCLOPHOSPHAMIDE.
Materials and methods:
The study was conducted on 32 male F 1 hybrid mice (CBAxC 57 B1) weighing 20-22 grams. The animals were divided into 4 groups, each of which contained 8 mice:
2. A group of mice that received ascorbigen per os at a dose of 100 mg/kg for 14 days.
3. Positive control group, in which animals received CP once intraperitoneally at a dose of 200 mg/kg.
4. A group of mice to which CP was administered a single intraperitoneal dose of 200 mg/kg (MPD), and after 24 hours oral administration of ascorbigen was started in a single dose of 100 mg/kg for 14 days.
On the first day after a 14-day course of ascorbigen administration (day 16 of the experiment), animals in the experimental and control groups were sacrificed, sections of the small intestine were fixed in 10% neutral formaldehyde, embedded in paraffin, and sections were stained with hematoxylin-eosin.
Results:
In areas of regeneration, which occur along with foci of destruction, the number of Packet cells did not differ from the norm. They contained a small number of small eosinophilic granules.
A 14-day administration of ascorbigen in a single dose of 100 mg/kg per os after a single intraperitoneal administration of CP at a dose of 200 mg/kg led on the 16th day of the experiment to an almost complete restoration of the structure of the villi and the lamina propria of the mucous membrane. Their damage was expressed only in the presence of small foci of edema. On individual villi in the apical region, zones of necrosis of the columnar epithelium remained.
In the area of the crypts, isolated cysts were preserved. Packet cells did not differ in morphological structure and number from the intact control. In some glands, Paneth cells were found in a state of vacuolar degeneration.
3. The influence of ascorbigen on the processes of repair of damage to the structure of lymphoid organs caused by the administration of CYCLOPHOSPHAMIDE.
Materials and methods:
The study was conducted on 24 male F 1 hybrid mice (CBAxC 57 B1) weighing 20-22 grams. The animals were divided into 3 groups, each of which contained 8 mice:
1. Intact control group.
2. Positive control group, in which animals received CP once intraperitoneally at a dose of 200 mg/kg.
3. A group of mice to which CP was administered a single intraperitoneal dose of 200 mg/kg (MPD), and after 24 hours oral administration of ascorbigen was started in a single dose of 100 mg/kg for 14 days.
Results:
Spleen.
Lymph node
4. Effect of ASCORBIGEN on leukocytopenia in mice caused by the use of CYCLOPHOSPHAMIDE.
Materials and methods.
The studies were conducted on male F 1 hybrid mice (CBAxC 57 Black) weighing 18-22 grams, obtained from the central nursery of the Russian Academy of Medical Sciences “Kryukovo”.
Cyclophosphamide (pharmacy CYCLOPHOSPHAMIDE) was dissolved in saline. solution and administered once intraperitoneally at a dose of 300 mg/kg on day 0.
ASCORBIGEN substance was dissolved in water and 1% concentration was injected into the stomach using a syringe with a metal cannula at a dose of 100 mg/kg daily for 14 days, starting from day zero.
Results.
It has been shown that CYCLOPHOSPHAMIDE by day 3 leads to a decrease in the total number of leukocytes to 500-1500 cells per mm 3. A second decrease in leukocytes to 7-10.5 thousand cells per mm 3 is observed. Recovery to normal occurs in 15-16 days. (Fig. 1)
Conclusion.
The use of ASCORBIGEN at a dose of 100 mg/kg daily for 14 days orally after a single intraperitoneal application of CIC-LOFOSPHAMIDE at a dose of 300 mg/kg accelerates the restoration of peripheral blood parameters to normal, and also helps to reduce the intestinal toxicity of the latter.
5. Antibacterial activity of ascorbigen (ASG).
Materials and methods:
The work used suckling mice of the SHK colony at the age of 3-4 days. Pregnant females SHK were obtained from the vivarium of VNIHFI (our own breeding). The females were monitored daily, and the dates of birth were recorded.
To obtain sepsis, 3-4-day-old mice were administered orally (via an elastic probe) a bacterial culture at a dose of 510 6 CFU/mouse. After 24 hours, the mice were examined, and the % of animal death was taken into account; Then the mice were dissected under sterile conditions and inoculated onto nutrient media by imprinting organs - spleen, liver, kidneys. In addition, blood was always taken from the heart for culture. For Staphylococcus aureus, yolk salt agar (YSA) was used; for sowing Gr-cultures - Levin's medium. To study the preventive effect of ASG in newborn mice, the litter of mice was conditionally divided into 2 groups; in the first group, starting from 3-4 days of age, mice were administered orally (through an elastic probe) ASH (at the rate of 100 mg/kg) for 7-8 days. The second group was the control group (without the administration of ASG). Mice in two groups were simultaneously orally administered Staphylococcus aureus (clinical isolate) at a dose of 510 6 CFU/mouse. After 24 hours of observation, the death of animals was taken into account; The pups, including the dead ones, were dissected under sterile conditions, and organs and blood from the heart were seeded onto the MFA using fingerprints.
Results:
As a result of oral infection with Staphylococcus aureus at a dose of 510 6 CFU of 3-4 day old mice, animal death was observed in 20-37.5% of cases.
When sowing on a selective nutrient medium (SMMA), positive or negative sowing was recorded (see table, drawing).
The table data shows that preliminary/prophylactic administration of ASG for 7 days was accompanied by a decrease in the % of seeding from the liver, kidneys and spleen by more than 2 times, and from the blood by 3 times compared to the control (animals that did not receive ASG).
In preliminary experiments using Gr-cultures of bacteria (E. coli, Proteus vulgaris, Klebsiella pneumoniae) to infect mouse pups, a sharp decrease in inoculability was also noted, especially pronounced when inoculating blood.
6. Effect of ascorbigen on alopecia caused by the administration of cyclophosphamide (CP)
The use of cytostatics, in particular CP, is often accompanied by the development of symptomatic alopecia (Symptomatic alopecia is complete or partial hair loss that develops as a symptom or complication of any disease, intoxication or skin damage) (syn.: symptomatic atrichia, symptomatic atrichosis, symptomatic baldness , symptomatic pelade, symptomatic baldness). Using a model, we have shown that intraperitoneal administration of 200 mg/kg CP to suckling mice on the 8-9th day of birth is accompanied by complete loss of hair in the next 4-5 days. Preliminary administration of ascorbigen at a dose of 100 mg/kg for 5 days before injection of CP reduces the severity (intensity) of alopecia, and subsequent administration of ascorbigen promotes more intensive restoration of hair growth (Fig. 1). The pups completely restored their hair 3-4 days earlier than the animals in the control group (without the administration of ascorbigen).
This was confirmed by morphological studies. Microscopic examination of the positive control group (mice that received CP once intraperitoneally at a dose of 100 mg/kg) revealed a number of pathological changes in the skin. They were expressed in thinning of the epidermal layer, moderate edema and fragmentation of collagen fibers of the dermis. There was no hair in some of the hair follicles. At the same time, individual cells of the matrix (cambial) layer and the muscle that lifts the hair were in a state of atrophy.
In mice that received ascorbigen before and after the administration of CP, the epidermis had no signs of damage, there was no swelling of the dermis, and the structure of the collagen fibers of the dermis and skin appendages was normal. The cells of the matrix layer of the hair follicle and the muscle that lifts the hair did not differ from the norm
The essence of the invention is illustrated by the following examples.
The study was conducted on 30 C 57 B1 mice and 20 F 1 hybrid mice (CBAxC 57 B1) males weighing 20-22 grams.
Animals received ascorbigen in single doses from 10 to 1000 mg/kg per stomach for 14 days. At the end of the course of administration, the animals were killed. Sections of the small intestine were fixed in a 10% solution of neutral formalin, embedded in paraffin according to the standard procedure, and short series of sections were stained with hematoxylin-eosin.
On the first day after the 14-fold administration of the drug, a sharp increase in the number of Paneth cells was found in the mucous membrane of the small intestine. In some glands, they were located not only in the area of the bottom of the gland, but also filled the entire crypt right up to the neck of the gland. If normally the ratio of Paneth cells and cambial elements of the cylindrical epithelium is 1:1, then with the use of ascorbigen it increases to 2:1. The number of eosinophilic granules in Paneth cells and their size also increased sharply. The lumen of the gland crypt was expanded and filled with granules released from Paneth cells by endocytosis.
In the villous area of the intestinal epithelium, the number of goblet cells increased.
In the lamina propria of the mucous membrane of the small intestine, proliferation of the capillary network was revealed according to the type of development of young granulation tissue.
An increase in the number of intraepithelial lymphocytes to 3-5 per gland was also noted, whereas in intact animals it was 1 per several glands.
Thus, an increase in the number and increased activity of Paneth cells, an increase in the number of intraepithelial lymphocytes, thickening of the lamina propria of the mucous membrane and an increase in mucus-forming goblet cells suggests that the drug ascorbigen, administered orally in the form of a 14-day course in single doses from 10 to 1000 mg/ kg, has the ability to enhance the protective function of the mucous membrane of the small intestine.
A group of male F 1 hybrid mice (CBAxC 57 B1) weighing 20-22 grams received CP intraperitoneally at a dose of 200 mg/kg (MPD), and after 24 hours oral administration of ascorbigen was started at a single dose of 100 mg/kg for 14 days.
On the first day after a 14-day course of administration, the animals were sacrificed, sections of the small intestine were fixed in 10% neutral formalin, embedded in paraffin, and sections were stained with hematoxylin-eosin.
In animals that received CP once intraperitoneally at a dose of 200 mg/kg, signs of damage to the mucous membrane remained in the small intestine on the 16th day after administration. They were expressed in the form of large foci of destruction of the epithelium of the glands, located mainly in the crypt area. In a number of glands, the lumen of the crypts is sharply expanded, in the lumen there is cellular detritus and a large number of large eosinophilic granules. In the damaged areas, Paneth cells were in a state of balloon degeneration. Their number has increased sharply. They are located not only in the area of the bottom of the glands, but extended up to the neck, increased in size and filled with many granules. Some Paneth cells are in a state of destruction.
The villi of the mucous membrane in the area of damage are thinned, some are in a state of destruction.
In the lamina propria of the mucous membrane, cell death, thinning of fibrous structures, and the formation of cyst-like cavities of various sizes were noted.
In areas of regeneration, which occur along with foci of destruction, the number of Paneth cells did not differ from the norm. They contained a small number of small eosinophilic granules.
In the villous area, regeneration occurred faster than in the crypt area. The regenerated villi are short and few in number.
A 14-day administration of ascorbigen in a single dose of 100 mg/kg per os after a single intraperitoneal administration of CP at a dose of 200 mg/kg led on the 16th day of the experiment to an almost complete restoration of the structure of the villi and the lamina propria of the mucous membrane.
Thus, oral administration of ascorbigen in the form of a 14-day course in a single dose of 100 mg/kg leads to an acceleration of the processes of repair of damage to the mucous membrane of the small intestine caused by a single administration of CP at a dose of 200 mg/kg.
A group of F 1 hybrid mice (CBAxC 57 B1) males weighing 20-22 grams of CP were administered a single intraperitoneal dose of 200 mg/kg (MPD), and after 24 hours oral administration of ascorbigen was started in a single dose of 100 mg/kg for 14 days.
On the first day after a 14-day course of ascorbigen administration (day 16 of the experiment), animals in the experimental and control groups were killed, the thymus, spleen and lymph nodes were fixed in 10% neutral formaldehyde, embedded in paraffin, sections were stained with hematoxylin-eosin.
CYCLOPHOSPHAMIDE. With a single intraperitoneal injection of CP into the IVD on day 7, a slight narrowing of the cortical zone, moderate atrophy of lymphoid tissue in both the cortical and medullary zones, and the appearance of cyst-like stretched sinuses in the medullary zone and at the border with the cortical zone were noted in the thymus. Moderate atrophy of the lymphoid tissue of the cortical and medullary zones of the thymus persists for two weeks after administration of the drug.
CF + Ascorbigen. A 14-day administration of ascorbigen after a single application of CP reduced the damaging effect of the latter on the lymphoid tissue of the thymus. The damaging effect on the 15th day after the use of CP was expressed only in a slight atrophy of lymphoid tissue in the brain zone.
Spleen.
CYCLOPHOSPHAMIDE. The administration of CP led to moderate atrophy of lymphoid tissue after 7 days of observation, which persisted until the 15th day of the experiment. The number of megakaryoblasts and megakaryocytes on day 7 was slightly increased. By 15 days it increases significantly. Foci of extramedullary hematopoiesis on day 7 are no more common than in the control group. 2 weeks after a single injection of CF, their number becomes significantly larger.
CF + Ascorbigen. When using ascorbigen in the form of a 14-day course the next day after a single administration of CP, on the 1st day after the end of ascorbigen administration (15 days after administration of CP), the number of foci of extramedullary hematopoiesis increased many times. Moreover, they were mainly of the myelocytic type. The number of megakaryocytes and megakaryoblasts also increased. No signs of lymphoid tissue atrophy were detected.
Lymph node
CYCLOPHOSPHAMIDE. On the 7th day after the administration of CP, moderate atrophy of lymphoid tissue in the cortical zone was found in the lymph nodes, which persisted until the 15th day of observation. By day 15, small foci of sclerosis can be seen under the lymph node capsule. Foci of myeloid hematopoiesis were found in the brain zone.
CF + Ascorbigen. The structure of the lymph nodes does not differ from the control.
Thus, oral administration of ascorbigen at a dose of 100 mg/kg for 14 days after a single intraperitoneal administration of CYCLO-PHOSPHAMIDE can accelerate the restoration of lymphoid tissue of the thymus, spleen and lymph nodes.
Male F 1 hybrid mice (CBAxC 57 B1) weighing 18-22 grams were administered a single dose of CP intraperitoneally at a dose of 300 mg/kg on day 0.
ASCORBIGEN substance was administered into the stomach using a syringe with a metal cannula at a dose of 100 mg/kg daily for 14 days, starting from day zero.
The condition and behavior of the animals were monitored daily; on days 3, 5, 8, 11 and 16, the weight of the animals was determined and peripheral blood was taken from the tail to determine the total number of leukocytes.
It has been shown that CYCLOPHOSPHAMIDE by day 3 leads to a decrease in the total number of leukocytes to 500-1500 cells per mm 3. A second decrease in leukocytes to 7-10.5 thousand cells per mm 3 is observed. Recovery to normal occurs in 15-16 days.
The use of ASCORBIGEN in the above regimen did not affect the level of the total number of leukocytes.
The use of ASCORBIGEN after CYCLOPHOSPHAMIDE prevented the development of deep cytopenia by the 3rd day. The level of leukocytes at this time was 1-3 thousand cells per mm 3. The restoration of the normal number of leukocytes occurred by 6 days. No recurrent decrease in leukocyte count was observed. Calculation of the leukocyte formula showed that the restoration of the level of leukocytes occurs due to neutrophils.
In the group of animals receiving CYCLOPHOSPHAMIDE, diarrhea developed from the 2nd day, and by the 5th day there was a decrease in body weight by 10%. (Fig. 2) Restoration of body weight to the initial level occurred only by the 12th day. When ASCORBIGEN was used against the background of CYCLOPHOSPHAMIDE, diarrhea was less pronounced and short-term in animals. No decrease in animal body weight was observed in this group.
The use of ASCORBIGEN at a dose of 100 mg/kg daily for 14 days orally after a single intraperitoneal application of CYCLOPHOSPHAMIDE at a dose of 300 mg/kg accelerates the restoration of peripheral blood parameters to normal, and also helps to reduce the intestinal toxicity of the latter.
To obtain sepsis, 3-4 day old mice were administered orally (via an elastic probe) a bacterial culture at a dose of 510 6 CFU/mouse. After 24 hours, the mice were examined, and the % of animal death was taken into account; Then the mice were dissected under sterile conditions and inoculated onto nutrient media by imprinting organs - spleen, liver, kidneys. In addition, blood was always taken from the heart for culture. For Staphylococcus aureus, yolk salt agar (YSA) was used; for sowing Gr-cultures - Levin's medium. To study the preventive effect of ASG in newborn mice, the litter of mice was conditionally divided into 2 groups; in the first group, starting from 3-4 days of age, mice were administered orally (through an elastic probe) ASH (at the rate of 100 mg/kg) for 7-8 days. The second group was the control group (without the administration of ASG). Mice in two groups were simultaneously orally administered Staphylococcus aureus (clinical isolate) at a dose of 510 6 CFU/mouse. After 24 hours of observation, the death of animals was taken into account; The pups, including the dead ones, were dissected under sterile conditions, and organs and blood from the heart were seeded onto the MFA using fingerprints.
As a result of oral infection with Staphylococcus aureus at a dose of 510 6 CFU of 3-4-day-old mice, animal death was observed in 20-37.5% of cases. When sowing on a selective nutrient medium (SMMA), positive or negative sowing was recorded. It was revealed that preliminary/prophylactic administration of ASG for 7 days was accompanied by a decrease in the % of seeding from the liver, kidneys and spleen by more than 2 times, and from the blood by 3 times compared to the control (animals that did not receive ASG).
In preliminary experiments using Gr - bacterial cultures (E. coli, Proteus vulgaris, Klebsiella pneumoniae) to infect mouse pups, a sharp decrease in inoculability was also noted, especially pronounced when inoculating blood.
Using suckling mice, the positive effect of ASG on the restoration of intestinal microflora during dysbacteriosis was shown. Oral administration of ASG (at a dose of 100 mg/kg) to mice with nonspecific enteritis accompanied by diarrhea for 3 days completely stopped the diarrhea. The mice began to eat actively and move more. Continuation of the administration of ASG for up to 10 days contributed to the improvement of quantitative indicators of intestinal microflora. For example, in mice that did not receive ASG, the content of Escherichia coli (E. coli), the main representative of the normal intestinal microflora, corresponded to 10 4 CFU per 1 g of feces. After a 10-day course of ASG (100 mg/kg, orally, daily), the E. coli content increased to 10 5 CFU per 1 g of feces. Quantitative indicators of anaerobic flora also approached normal. The level of bifidobacterium and lactobacilli increased from 10 4 CFU and 10 7 CFU to 10 5 CFU and 10 8 CFU per 1 g of feces, respectively. It should be noted that mice that did not receive ASG died in 80% of cases.
On days 8-9 from birth, suckling mice were administered 200 mg/kg CP intraperitoneally. After 4-5 days they experienced complete loss of hair. Preliminary administration of ascorbigen at a dose of 100 mg/kg for 5 days before injection of CP reduces the severity (intensity) of alopecia, and subsequent administration of ascorbigen promotes more intensive restoration of hair growth (Fig. 1). The pups completely restored their hair 3-4 days earlier than the animals in the control group (without the administration of ascorbigen).
This was confirmed by morphological studies. Microscopic examination of the positive control group (mice that received CP once intraperitoneally at a dose of 100 mg/kg) revealed a number of pathological changes in the skin. They were expressed in thinning of the epidermal layer, moderate edema and fragmentation of the collegene fibers of the dermis. There was no hair in some of the hair follicles. At the same time, individual cells of the matrix (cambial) layer and the muscle that lifts the hair were in a state of atrophy.
In mice that received ascorbigen before and after the administration of CP, the epidermis had no signs of damage, there was no swelling of the dermis, and the structure of the collagen fibers of the dermis and skin appendages was normal. The cells of the matrix layer of the hair follicle and the muscle that lifts the hair did not differ from the norm.
Thus, the use of ascorbigen in the studied dose and regimen prevented the development of atrophic changes in the skin of newborn mice that occur under the influence of CP.
In general, the presented materials confirm the advantages of the claimed method, namely: the possibility of increasing nonspecific resistance to infectious and toxic agents, which makes it possible to reduce the risk of developing a serious disease and speed up the recovery of patients.
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CLAIM
1. A method of increasing nonspecific resistance of the body, including the administration of a medicinal product, characterized in that ascorbigen is used as a medicinal product, which is administered in courses at a dose of 10 mg/kg daily for 5-30 days.
2. The method according to claim 1, characterized in that ascorbigen is administered after completing a course of mono- or polychemotherapy with cytotoxic drugs.
3. The method according to claim 1, characterized in that ascorbigen is administered for a bacterial infection.
4. The method according to claim 1, characterized in that ascorbigen is administered for alopecia caused by cytotoxic drugs.
Resistance (from lat. resistere - resist, resist) - the body’s resistance to the action of extreme stimuli, the ability to resist without significant changes in the constancy of the internal environment; this is the most important qualitative indicator of reactivity;
Nonspecific resistance represents the body’s resistance to damage (G. Selye, 1961), not to any individual damaging agent or group of agents, but in general to damage, to various factors, including extreme ones.
It can be congenital (primary) and acquired (secondary), passive and active.
Congenital (passive) resistance is determined by the anatomical and physiological characteristics of the organism (for example, the resistance of insects, turtles, due to their dense chitinous cover).
Acquired passive resistance occurs, in particular, with serotherapy and replacement blood transfusion.
Active nonspecific resistance is determined by protective-adaptive mechanisms and arises as a result of adaptation (adaptation to the environment), training to a damaging factor (for example, increased resistance to hypoxia due to acclimatization to a high-mountain climate).
Nonspecific resistance is provided by biological barriers: external (skin, mucous membranes, respiratory organs, digestive apparatus, liver, etc.) and internal - histohematic (blood-brain, hemato-ophthalmic, hematolabyrinthine, hematotesticular). These barriers, as well as biologically active substances contained in fluids (complement, lysozyme, opsonins, properdin) perform protective and regulatory functions, maintain the optimal composition of the nutrient medium for the organ, and help maintain homeostasis.
FACTORS REducing NON-SPECIFIC RESISTANCE OF THE ORGANISM. WAYS AND METHODS OF ITS INCREASE AND STRENGTHENING
Any impact that changes the functional state of regulatory systems (nervous, endocrine, immune) or executive (cardiovascular, digestive, etc.) leads to a change in the reactivity and resistance of the body.
Factors that reduce nonspecific resistance are known: mental trauma, negative emotions, functional inferiority of the endocrine system, physical and mental fatigue, overtraining, fasting (especially protein), malnutrition, lack of vitamins, obesity, chronic alcoholism, drug addiction, hypothermia, colds, overheating, painful injury, detraining of the body and its individual systems; physical inactivity, sudden changes in weather, prolonged exposure to direct sunlight, ionizing radiation, intoxication, previous diseases, etc.
There are two groups of pathways and methods that increase nonspecific resistance.
With a decrease in vital activity, loss of the ability to exist independently (tolerance)
2. Hypothermia
3. Ganglioblockers
4. Hibernation
When maintaining or increasing the level of vital activity (SNPS - a state of non-specifically increased resistance)
1 1. Training of basic functional systems:
Physical training
Hardening to low temperatures
Hypoxic training (adaptation to hypoxia)
2 2. Changing the function of regulatory systems:
Autogenic training
Verbal suggestion
Reflexology (acupuncture, etc.)
3 3. Non-specific therapy:
Balneotherapy, spa therapy
Autohemotherapy
Protein therapy
Nonspecific vaccination
Pharmacological agents (adaptogens - ginseng, Eleutherococcus, etc.; phytocides, interferon)
To the first group These include impacts through which resilience is increased due to the body’s loss of the ability to exist independently and a decrease in the activity of vital processes. These are anesthesia, hypothermia, hibernation.
When an animal in hibernation is infected with plague, tuberculosis, or anthrax, the diseases do not develop (they occur only after it awakens). In addition, resistance to radiation exposure, hypoxia, hypercapnia, infections, and poisoning increases.
Anesthesia increases resistance to oxygen starvation and electric current. In a state of anesthesia, streptococcal sepsis and inflammation do not develop.
With hypothermia, tetanus and dysentery intoxication are weakened, sensitivity to all types of oxygen starvation and to ionizing radiation is reduced; increased resistance to cell damage; allergic reactions are weakened, and in the experiment the growth of malignant tumors is slowed down.
In all these conditions, there is a deep inhibition of the nervous system and, as a consequence, of all vital functions: the activity of regulatory systems (nervous and endocrine) is inhibited, metabolic processes are reduced, chemical reactions are inhibited, the need for oxygen is reduced, blood and lymph circulation slows down, and the temperature drops body, the body switches to a more ancient metabolic pathway - glycolysis. As a result of the suppression of normal life processes, active defense mechanisms are switched off (or inhibited), and a non-reactive state arises, which ensures the body’s survival even in very difficult conditions. At the same time, he does not resist, but only passively tolerates the pathogenic effect of the environment, almost without reacting to it. This condition is called tolerability(increased passive resistance) and is a way for the body to survive in unfavorable conditions, when it is impossible to actively defend itself and avoid the action of an extreme irritant.
To the second group The following methods of increasing resistance while maintaining or increasing the level of vital activity of the body include:
Adaptogens are agents that accelerate adaptation to adverse effects and normalize disorders caused by stress. They have a broad therapeutic effect, increase resistance to a number of factors of a physical, chemical, biological nature. The mechanism of their action is associated, in particular, with their stimulation of the synthesis of nucleic acids and proteins, as well as with the stabilization of biological membranes.
By using adaptogens (and some other medications) and adapting the body to the action of unfavorable environmental factors, it is possible to create a special condition nonspecifically increased resistance - SNPS. It is characterized by an increase in the level of vital activity, mobilization of active defense mechanisms and functional reserves of the body, and increased resistance to the action of many damaging agents. An important condition for the development of SNPS is a dosed increase in the force of exposure to unfavorable environmental factors, physical activity, and the elimination of overloads, in order to avoid disruption of adaptation-compensatory mechanisms.
Thus, the organism that is more resistant is the one that resists better, more actively (SNPS) or is less sensitive and has greater tolerance.
Managing the reactivity and resistance of the body is a promising area of modern preventive and therapeutic medicine. Increasing nonspecific resistance is an effective way to generally strengthen the body.
