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11СОСТОЯНИЕ ИММУННОЙ РЕАКТИВНОСТИ У ЭКСПЕРИМЕНТАЛЬНЫХ ЖИВОТНЫХ С КАРЦИНОМОЙ WALKER 256, НА ФОНЕ ОБЩЕЙ ГИПЕРТЕРМИИ
Е.А. Васькина1, О.Ж. Узаков2, A.B. Ефремов1
'Новосибирский Государственный Медицинский Университет, Новосибирск, Россия Международная Высшая Школа Медицины, Бишкек, Кыргызстан
Аннотация
В статье представлены показатели иммунитета крыс с карциносаркомой Walker 256 в период развития опухолевого процесса и воздействия общей гипертермии. Полученные данные свидетельствуют о том, что воздействие общей гипертермии на организм экспериментальных животных с карциносаркомой Walker 256 сопровождается разнонаправленными изменениями параметров иммунной системы как в сторону их снижения, так и увеличения в различные сроки после гипертермии. . Это может быть связано с активацией эндогенных регуляторных систем, определяющих иммунную реактивность организма.
Ключевые слова: карциносаркома Walker 256, гуморальный и клеточный иммунитет, общая гипертермия.
Introduction
The immunological reactivity of organisms with tumor growth remains one of the most important scientific problems in modern medicine. The question of why, despite sufficient immune reactivity, tumor cells arise and grow, which differ significantly in their morphological and functional parameters, capable of not only suppressing but also stimulating the immunological properties of the body, is not only a central issue in pathophysiology but also oncology, immunology, and genetics.
It is known that tumor growth is a systemic pathological process that affects the entire body, all links of its immunogenetic and neuroendocrine regulation. Therefore, the problem of stimulating immunity and studying "body-tumor" interactions is important not only in terms of preventing potential tumor growth but also in terms of studying the dynamics of these processes, especially in the late stages of the tumor process [1,11]. The relationship of the tumor with the body's immune system has two aspects: specific, associated mainly with cytotoxic lymphocytes, and non-specific, defined as part of the systemic interaction of the tumor and the body.
The traditional areas of medicine concerning the antitumor protective systems of the body are their stimulation with pharmacological agents, natural mechanisms, and vital products of
immunocompetent cells: interferons, lymphokines, targeted lymphocytic cell, and gene therapy.
The immunomodulatory effects of physical exposure to tumor tissue have not been studied. In this sense, the most promising methods are general hyperthermia (GH), which not only affects tumor tissue, but also stimulates apoptosis [2], and systemic and local mechanisms of the immune response [9]. In general, GH remains one of the effective modifiers of traditional antitumor therapy. But the clinical use of GH should be preceded by its experimental modeling with the aim of a more complete and detailed study of the hematogenesis and pathogenetic aspects of the heating exposure to cells, tissues, organs, and the body as a whole.
Material and Methods
The object of study. The studies were carried out on 90 male Wistar rats (2.5 months old, weight - 220-250 g.) from the vivarium of the Central Research Laboratory of NSMU. For the experiment, we used animals kept in vivarium conditions. The care and maintenance of experimental animals was standard following the requirements of the orders "Sanitary regulations for the establishing, equipment and maintenance of vivariums" dated 06.041973 No. 1045-73, as well as No. 1179 of the Ministry of Health of the USSR of 10.10.1983, No. 267 of the Ministry of Health of the Russian Federation of
19.06. 2003, "Rules for the handling, keeping, anesthetizing and killing of experimental animals", approved by the Ministry of Health of the USSR (1977) and the Ministry of Health of the RSFSR (1977), the principles of the European Convention (Strasbourg, 1986) and the Helsinki Declaration of the World Medical Association for the Humane Treatment of Animals (1996). Rats were kept in the vivarium of the University at 12 hours of illumination, room temperature 20±2 ° C, humidity 50-70%. Animal feeding was carried out following the established diet with the use of compound feed for laboratory rats and mice "ProKorm" produced by the joint-stock company "BioPro" (factory article R-22; State StandardR 50258-92) (Russia).
All experimental studies were carried out in winter and spring at the same time - from 9 to 13 hours.
Experimental models. The heating of the animals was carried out in full accordance with the "Method of experimental modeling of general hyperthermia in small laboratory animals" [5]. The proposed method for experimental modeling of general hyperthermia (OG) involves heating the experimental animals in the tank of a water thermostat BWT-U, designed to accurately maintain the set temperature of water in the range from + 25 °C to + 100 °C when immersed in hot water to neck level. Water was heated at a set temperature and maintained automatically with uniform mixing of its layers, which allows us to consider the temperature of the water coolant in the experiment as a constant value. The advantage of modeling GH in an aqueous medium over an air one is that it provides a uniform, deep, and rapid heating of the animal's body [8,12]. The temperature regime was selected experimentally and amounted to 45 °C. This temperature is optimal when modeling GH since rats tolerate poorly higher temperatures and die [3 ].
The heating time of each animal to a level of rectal temperature of 43.5 ° C was individual, depended on neither the initial temperature of the body nor the mass of the animal and was no more than 17 minutes [10] explained such a rapid increase in body temperature when heated in conditions of 90-100% humidity by the complete cessation of the evaporation of sweat and, thereby, the absence of effective cooling. The level of GH at which heating was stopped we determined by a rectal temperature of 43.5 °C (stage of heatstroke). A higher degree of heating resulted in the death of the animals at the
time of exposure or in the early stages of the post-heating period, because the temperature range that rats can endure is within these limits. When measuring the rectal temperature of heated animals, one of the junctions of the differential thermocouple was inserted into the rectum to a depth of 3-4 cm, and the second was lowered into melting ice (Dewar vessel). The temperature differences between 0 °C and rectal temperature were expressed in microvolts on the microvoltmeter.
The experiment consisted of several stages.
1st stage. All animals were exposed to GH once.
2nd stage. The tumor was transplanted into the experimental animals.
3rd stage. In animals of this group, against the background of a transplanted tumor, a single GH exposure was used.
To simulate the tumor process in the experimental animals, we used the Walker-256 transplantable carcinosarcoma tumor strain, supported in vivo (Laboratory of Physiological Genetics, Research Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk). A suspension of Walker-256 transplantable carcinosarcoma cells was administered to animals in the muscle of the back of the thigh at a dose of 1 x 106 cells in 0.1 ml of isotonic NaCl solution. Animals were killed by decapitation under ether anesthesia on the 1 st, 3rd, 7th, 14th, and 21 st days after GH. The control group included seven intact rats of the same breed.
Study Methods. An immunological study was carried out by determining monoclonal antibodies (mAbs) to CD3, CD4, CD8, and CD20 antigens in a direct or indirect immune fluorescence reaction considering the results on a flow photometer or a luminescent microscope. To determine T-lymphocytes, T-helpers, and T-suppressors, we used diagnostic agents, which are fixed latex coated with monoclonal antibodies against CD3 (T-lymphocytes), CD4 (T-helpers), CD8 (T-suppressors), CD 16 (NK cells). Also, we calculated the immunoreactive index as the ratio of the percentage of T-helpers and T-suppressors (CD4 / CD8). To determine B-lymphocytes, we used erythrocytes coated with antibodies to CD20 antigen-specific for B cells [7,13].
The parameters of humoral immunity (Ig A, M, and
G classes) were determined by the method of automated kinetic nephelometry on the Immunochemical System instrument using monospecific serums against Ig A, M, and G (the principle is based on measuring the rate of increase in light scattering intensity due to particles formed by the antigen-antibody reaction). Calculation of the absolute value of immunoglobulins was carried out according to calibration graphs constructed according to one series of anti-immunoglobulins.
values. Differences were considered statistically significant atp <0.05.
Research findings
Research of degree of change in the humoral link of the immune system during transplantation of tumor carriers (Walker 256 carcinosarcoma) revealed several patterns in the body's response under these conditions to the effect of artificial hyperthermia.
Table 1 presents data on the dynamics of the content of circulating immune complexes (CIC) in the blood serum after exposure to GH.
When analyzing CIC in the blood serum of animals with the experimental tumor, after the use of GH, as well as with a combination of tumor growth and GH, the following changes were revealed. In animals of the control group, this indicator was 21.8 ± 1.79 conventional units. When studying the effect of GH on the CIC content in serum, it was noted that on the 1st day of the post-heating period, the studied parameter did not differ from the control values. The period from the 3rd to the 7th day of observation was marked by an increase in the content of CIC in the
We evaluated the concentration of circulating immune complexes (CIC) by the method of liquid precipitation of 4% PEG-600 [6,14].
The data obtained were processed using methods of variation statistics [Giants S., 1999] by calculating the arithmetic mean (M), standard error of the mean (m). Tables present data as M±m. We calculated dissimilarities in parameters by the method of difference statistics using a t-test for dependent
blood serum: on the 3rd day - by 30% (28.31 ± 1.47 units), on the 7th day-by 20% (25.8 ± 1.91 units).By the 14th day, this indicator returned to the control values.
In animals with transplantable Walker 256 carcinosarcoma on the 3rd, there was an increase in the content of CIC in the blood serum to 25.93 ± 1.96 units. By the 7th day, this indicator decreased to values that do not differ from those in the control group of animals. And by the 14th day, the content of CIC in serum decreased to 17.04 ± 1.97 units (-19% relative to the control group).
In the group of animals with Walker 256 carcinosarcoma exposed to GH, there was an increase in the content of CIC in the blood serum from the 3rd to the 7th day of observation (27.89 ± 2.319 units and 26.56 ± 2.07 units respectively). After the 7th day of observation, the indicator studied did not differ from that in animals of the control group.
When investigating the level of immunoglobulin M (IgM) in experimental animals with experimental tumor growth, after the use of GH and with the
Table 1. The content of CIC in the blood of experimental animals without a tumor and with Walker 256 carcinosarcoma after exposure to general hyperthermia (conventional unit)
Days of observation Hyperthermia Tumor Hyperthermia
(M±m) (Mim) + tumor (Mim)
Control 21.8±1.79
1st day 19.4±1.04 20.98i2.03 22.04il.88
3rd day 28.31il.47* 25.93il.96* 27.89i2.319*
7th day 25.8il.91 * 23.02i2.21 26.56i2.07 *
14th day 18.0Ü0.99 17.04il.97 * 20.22il.68
Note: * - marked values differ significantly from those of control group
Table 2. Dynamics of blood IgM in experimental animals without a tumor and with Walker 256 carcinosarcoma after exposure to general hyperthermia (g/L)
Days of observation Hyperthermia Tumor Hyperthermia
(M±m) (M±m) + tumor (M ± m)
Control 0.78±0.062
1st day 0.55±0.051 * 0.94±0.082 * 0.58±0.044 *
3rd day 0.81±0.064 1.11±0.077* 0.91±0.051 *
7th day 0.94±0.078 * 0.89±0.084 0.88±0.062
14th day 1.02±0.087 * 0.64±0.039 * 0.73±0.071
Note: * - marked values differ significantly from those of control group
combination of a tumor and GH (Table 2), we found that the serum IgM content in the control group was 0.78±0.062 g/L.
The next day after exposure to GH, we observed a decrease in the studied parameter by 25% in animals without tumor, which amounted to 0.55±0.051 g/L. By the 3rd day of observation, the serum IgM content in experimental animals of this group was restored to control values. In the period from the 7-14th day after exposure to GH, this parameter exceeded the control values by 20-23%.
In the group of animals with Walker 256 transplanted carcinosarcoma, from the 1st to the 3rd day of observation, an increase in serum IgM content was
observed: on the 1st day - 0.94 ± 0.082 g/L, on the 3rd day -1,11±0.077 g/L. On the 7fh day, this parameter did not differ from the control values. By the 14th day of observation, the IgM content in the blood serum of experimental animals decreased by 25% and amounted to 0.64±0.039 g/L.
In the group of animals with carcinosarcoma exposed to general hyperthermia, on the 1st day after the procedure, there was a decrease in the serum IgM content to 0.58±0.044 g/L. On the 3rd day of observation, this indicator increased by 24% and amounted to 0.91±0.051 g/L.
From the 7-14th day of observation, the serum IgM content did not differ from the control values.
Table 3. Dynamics of blood IgG in experimental animals without a tumor and with Walker 256 carcinosarcoma after exposure to general hyperthermia (g/L)
Days of observation Hyperthermia (M±m) A tumor (M ± m) Hyperthermia + tumor (M ± m)
Control 5.2±0.39
1st day 3.92±0.26 * 5.44±0.27 4.13±0.32 *
3rd day 4.41±0.68 7.23±0.63 * 6.48±0.51 *
7th day 6.75±0.68 * 5.31±0.34 7.04±0.53 *
14th day 7.12±0.57 * 3.94±0.25 * 4.88±0.39
Note: * - marked values di: Ter significantly from those of control group
The content of immunoglobulin G (IgG) in the blood serum of experimental animals of the control group was 5.2 ± 0.39 g/L (Table 3).
In animals exposed to GH on the 1st day of the post-heating period, there was a decrease in this parameter by 20%, which amounted to 3.92 ± 0.26 g/L. By the 3rd day of observation, the content of IgG in blood serum in animals of this group was restored to control values. In the period from the 7th to the 14th
day after the GH exposure, IgG content exceeded the control values by 20-22%.
In the group of animals with Walker 256 transplanted carcinosarcoma, the period on the 1st day of observation did not differ from the control values. On the 3rd day, there was an increase in the content of IgG in serum to 7.23 ± 0.63 g/L. By the 7th day, IgG was restored to control values. On the 14th day of observation, the content of IgG in the blood serum
decreased and amounted to 3.94 ± 0.25 g/L.
In the group of animals with Walker 256 carcinosarcoma exposed to GH, on the 1st day after the procedure, there was a decrease in the IgG content in the blood serum of experimental animals to 4.13 ± 0.32 g/L. On the 3rd day of observation, IgG content increased by 25% and amounted to 6.48 ± 0.51 g/L. On the 7th day of observation, the serum IgG content continued to increase and was equal to 7.04 ± 0.53 g/L. By the end of the experiment, the
IgG content returned to the control values.
When studying the level of immunoglobulin A (Ig A) in the blood serum of experimental animals with a tumor, after the use of GH and with the combination of tumor and GH, it was revealed (Table 4 ) that the content of Ig A in the blood serum of experimental animals the control group was 0.49 ± 0.031 g/L. In animals exposed to GH on the 1st day after the procedure, a decrease of Ig A by 42% was noted, which amounted to 0.26 ± 0.019 g/L. On other
Table 4. The dynamics of the content of Ig in the blood of experimental animals without tumors and with Walker 256 carcinosarcoma after exposure to general hyperthermia (g/L)
Days of observation Hyperthermia Tumor Hyperthermia
(M±m) (M±m) + tumor (M±m)
Control 0.49±0.031
1st day 0.26±0.019 * 0.51±0.029 0.42±0.029
3rd day 0.41±0.028 0, 69±0,042 * 0.48±0.034
7th day 0.52±0.039 0.43±0.023 0.38±0.031 *
14th day 0.45±0.027 0.32±0.019 * 0.37±0.028 *
Note: * - marked values differ significantly from those of control group
days of observation, the content of Ig A in the blood serum of experimental animals did not differ from the control values.
In the group of animals with Walker 256 transplantable carcinosarcoma, we observed a wave-like dynamics of this parameter: an increase in the content of Ig A in the blood serum on the 3rd day (0,69 ± 0.042 g/L) and a decrease of 30% by the 14th day (0.32 ±0.019 g/L).
In the group of animals with Walker 256 carcinosarcoma exposed to GH, there was a decrease in the content of Ig A in the blood serum from the T day (0.38 ± 0.031 g/L) to the 14th day (0.37 ± 0.028 g/L). On other days of observation, the
content of Ig A in serum did not differ from the control values.
When analyzing the content of lymphocytes in the blood serum of experimental animals with a tumor, after the use of GH and with the combination of a tumor and GH, the following changes were revealed (Table 5). In animals of the control group, this indicator was 2.57± 0.18xl09/L. When studying the effect of GH on the lymphocyte count in the blood serum, it was noted that on the 1st day after the procedure, lymphocyte number decreased by 28% and amounted to 1.88±0.14x 109/L. On the 3rd day of the experiment, the lymphocyte count of animals of this group did not differ from the control values.
Table 5. Dynamics of blood lymphocyte content in experimental animals without a tumor and with Walker 256 carcinosarcoma after exposure to general hyperthermia (109/L)
Study Dates Hyperthermia Tumor Hyperthermia
(M±m) (M±m) + tumor (M ± m)
Control 2.57±0.18
1st day 1.88±0.14 * 2.78±0.19 2.05±0.23 *
3rd day 2.35±0.33 4.98±0.33 * 3.86±0.28 *
7th day 3.18±0.23 * 3.79±0.24 * 2.76±0.21
14th day 4.39±0.51 * 1.94±0.17 * 2.01±0.19 *
Note: * - marked values di: ïer significantly from those of control group
The period from the 7th to the 14th day of observation was marked by an increase in the lymphocyte count: on the 7th day - by 24% (3.18 ± 0.23x107L), on the 14th day - by 3 8% (4.39 ± 0.51 xl O'/L).
Discussion
On the 3rd of observation, in animals with Walker 256 transplantable carcinosarcoma, lymphocyte count increased to 4.98 ± 0.33 xlO'/L. By the T day, there was a decrease in lymphocyte content to 3.79 ± 0.24 x109/L, but at the same time, it exceeded the control values by 50%. And by the 14th day, the lymphocyte count decreased to 1.94 ± 0.17 xl09/L (-21% compared to the control group).
In the group of animals with Walker 256 carcinosarcoma exposed to GH, there was a decrease in the lymphocyte count to 2.05 ± 0.23 xl09/L on the 1st day of the experiment. On the 3rd day, lymphocyte content increased by 51% and amounted to 3.86 ±
lymphocyte count in experimental animals amounted to 71.28 ± 2.515. On other days of observation, the studied parameter in animals of this group did not significantly differ from the control values.
In the group of animals with Walker 256 transplanted carcinosarcoma, the content of CD3 blood lymphocytes had the following dynamics: by the 3rd day of observation, the studied parameter increased to 65.89 ± 3.44%, and by the end of the experiment it decreased to 46.9 ± 3.25 %
In the group of animals with Walker 256 carcinosarcoma exposed to GH, a different dynamics was observed in the change in CD4 lymphocyte count: on the 1st day of observation, this indicator decreased by 14% (53.34 ± 3.03%), and by 3rd and the
0.28 xl 09/L. On the 7th day, the lymphocyte count did not differ from that in the animals of the control group. And by the end of the experiment (day 14), a decrease in the lymphocyte count amounted to 2.01 ±0.19 xl 09/L (-20% compared to the control values). When comparing the studied parameter between groups of animals, we found that in animals of the 3rd experimental group, the lymphocyte content was lower than in animals of the 2nd group at all periods of observation.
When analyzing CD3 lymphocyte count in the blood of experimental animals with a tumor, after the use of GH and when the tumor and GH were combined, we revealed the following changes: (Table 6).
In animals of the control group, this indicator was 59.9 ± 2.6%. In animals of the first group exposed to only GH, on the 1st day of observation, there was a decrease in CD3 lymphocyte count in the blood to 48.42 ± 2.01%. On the T, an increase in CD3
7th day returned to the control values. By the 14th day, the content of CD3 blood lymphocytes again decreased and reached 51.63 ± 3.54%. At the same time, differences in the studied parameter in animals of different experimental groups were noted. In the group of animals exposed to only GH, the content of CD3 blood lymphocytes during the period from the 7th to the 14th day of the experiment was higher than in animals of other groups.
The content of CD4 lymphocytes in the blood in experimental animals of the control group was 31.7 ± 2.72%. In the group of animals exposed to GH, the following dynamics was observed (Table 7): on the 1st day, CD4 lymphocyte count decreased to 26.48 ± 1.41 % (-20% relative to the control values), on the 3rd day of observation did not differ from the control
Table 6. The dynamics of CD3 lymphocyte count in the blood in experimental animals without a tumor and with Walker 256 carcinosarcoma after exposure to general hyperthermia (%)
Days of observation Hyperthermia Tumor Hyperthermia
(M±m) (M±m) + tumor (M ± m)
Control 59.9± 2.6
1st day 48.42±2.01 * 60.36±4.72 53.34±3.03 *
3rd day 63.54±1.98 65.89±3.44 * 63.89±3.51
7th day 71.28±2.51 * 52.3±4.06 * 57.34±3.33
14th day 62.41±3.02 46.9±3.25 * 51.63±3.54 *
Note: * - marked values differ significantly from those of control group
values. On the 7th day of the post-heating period, the maximum values of CD4 lymphocytes were recorded in animals of the first group - 38.19 ± 2.34%. By the end of the experiment (day 14), CD4 lymphocyte count in the blood of experimental animals decreased to 35.76 ± 2.54%, but this was higher than the control values.
the change in the CD4 lymphocyte count: on the 3rd day, this indicator increased by 16% (34.98 ± 2.43%), and on the 7th day decreased by 17% (27.43 ± 1.95%). On other days of observation, no significant differences were recorded.
When counting CD8 lymphocytes in the blood of experimental animals with experimental tumor process, after the use of GH and when the tumor and GH were combined, we found (Table 8) that CD8 lymphocyte count of the control group was 18.41 ± 1.44 %. In animals of the first group exposed to only
In animals with Walker 256 transplanted carcinosarcoma, an increase in CD4 lymphocyte count to 36.28 ± 2.07% was observed on the 3rd day. Starting from the 7th day of observation, the studied parameter decreased, reaching 27.37 ± 1.98% by the 7th day, and by 24.7 ± 2.17% by the 14th day. In the group of animals with Walker 256 carcinosarcoma exposed to GH, we observed a wavelike dynamics in
GH, on the 1st day of observation, there was a decrease in CD8 lymphocyte count to 15.25 ± 1.32%. On other days of observation, this parameter in animals of this group did not significantly differ from the control values.
In the group of animals with transplantable Walker 256 carcinosarcoma and the group of animals with Walker 256 carcinosarcoma exposed to GH, changes in CD8 lymphocyte count did not show any significant differences compared to the control values. But at the same time, differences in the
Table 8. The dynamics of CD8 lymphocyte count in the blood in experimental animals without a tumor and with Walker 256 carcinosarcoma after exposure to general hyperthermia (%)
Days of observation Hyperthermia Tumor Hyperthermia
(M±m) (M±m) + tumor (M ± m)
Control 18.41±1.44
1st day 15,25±1.32* 18.78±1.65 16.28±1.32
3rd day 19.56±1.50 21.02±3.12 17.43±1.25
7th day 18.79±1.08 19.67±1.81 18.57il.61
14th day 17.23±1.12 16.43±1.21 17.59il.23
Note: * - marked values differ significantly from those of control group
Table 7. The dynamics of CD4 lymphocyte count in the blood in experimental animals without a tumor and with Walker 256 carcinosarcoma after exposure to general hyperthermia (%)
Days of observation Hyperthermia Tumor Hyperthermia
(Mim) (Mim) + tumor (M i m)
Control 31.7i2.72
1st day 26.48il.41 * 31.05i2.73 27.45i2.13
3rd day 29.34i2.07 36.28i2.07 * 34.98i2.43 *
7th day 38.19i2.34* 27.37il.98 * 31.24i2.06
14th day 35.76i2.54 * 24.7i2.17 * 27.43il.95 *
Note: * - marked values differ significantly from those of control group
studied parameter in animals of the 2nd and 3rd carcinosarcoma exposed to GH, the change in CD8 experimental groups on the 1st and 3rd day of lymphocyte count was lower than in animals with observation were noted. In the group of animals with the only tumor.
Table 8. The dynamics of CD8 lymphocyte count in the blood in experimental animals without a tumor and with Walker 256 carcinosarcoma after exposure to general hyperthermia (%)
Days of observation Hyperthermia Tumor Hyperthermia
(M±m) (Mim) + tumor (Mim)
Control 18.41il.44
1st day 15,25±1.32 * 18.78il.65 16.28il.32
3rd day 19.56±1.50 21.02i3.12 17.43il.25
7th day 18.79il.08 19.67il.81 18.57il.61
14th day 17.23il.12 16.43il.21 17.59il.23
Note: * - marked values differ significantly from those of control group
When analyzing the content of CD20 lymphocytes in the blood of experimental animals with experimental tumor process, after the use of GH and with the combination of a tumor and GH, we revealed the following changes: (Table 9)
In animals of the control group, this indicator was 14.03 ± 1.36%. In the animals of the first group exposed to only GH, on the 1st day of observation, there was a decrease in the CD20 lymphocyte content in the blood to 11.17 ± 1.05%. On the 3rd day of the post-heating period, CD20 lymphocyte count did not differ from the control values; from the 7th to the 14th day of observation, CD20 lymphocyte content in the blood of this group exceeded the
control values and amounted to 17.09 ± 1.77% and 16,74 ± 1.34%, respectively.
In the group of animals with Walker 256 transplanted carcinosarcoma, there was a change in CD20 lymphocyte count on the 3rd day of observation, when this indicator increased and amounted to 18.17 ±
I.44%. Then CD20 lymphocyte count gradually decreased, and by the 14th day, it amounted to 9.26 ± 0.79%. In the group of animals with Walker 256 carcinosarcoma exposed to GH, a change in the CD20 content of blood lymphocytes was observed only on the 14th day of observation and amounted to
II.52 ±0.88%.
We calculated that the immunoregulatory index in the animals of the control group was 1.72 ± 0.17 units
Table 9. The dynamics of CD20 lymphocyte count in the blood in experimental animals without a tumor and with Walker 256 carcinosarcoma after exposure to general hyperthermia (%)
Days of observation Hyperthermia Tumor Hyperthermia
(Mim) (Mim) + tumor (M i m)
Control 14.03il.36
1st day ll.17il.05 * 14.87il.23 12.1Ü0.91
3rd day 13.38il.22 18.17il.44 * 16.46il.77
7th day 17.09il.77 * 13.41il.17 14.79il.57
14th day 16.74il.34* 9.26i0.79 * 11.52i0.88*
Note: * - marked values differ significantly from those of control group
(Table. 1 0), and in animals exposed to GH on the 3rd day of the post-heating period, a decrease by 15% was noted, which amounted to 1.45 ± 0.09 units. From the 7th to the 14th day after the exposure to the GH, the immunoregulatory index exceeded the
control values by 15 -17%.
In the group of animals with transplantable carcinosarcoma Walker 256, from the 1st to the 3rd day of observation, there were no significant differences between the studied parameter and control values.
And from the 7th to the 14th day, an increase of the immunoregulatory index was noted. So on the 7th day of observation, this indicator was 1.39 ± 0.08 units, and on the 14th day-1.5 ±0.11 units.
In the group of animals with Walker 256 carcinosarcoma exposed to GH, only on the 3rd day of the post-heating period there was an increase in the immunoregulatory index up to 2.0 ±0.18 units. On other days of observation, this indicator did not differ from the control values.
When analyzing the differences of the immunoregulatory index between the groups, we revealed the following features. On the 1st day of observation, the immunoregulatory index in all groups of animals did not differ both from the control values and between the groups. On the 3rd day of observation, the immunoregulatory index in the 1st group of animals was lower than in other experimental groups. The period from the 7th to the 14th day of the experiment was marked by the highest values of the immunoregulatory index in the group of animals exposed to only GH. It exceeded both control values and indicators in other experimental groups.
Conclusions
1. With a combination of general hyperthermia and the tumor process in experimental animals, a less pronounced suppression of the activity of the humoral component of the immune system in the body was noted.
2. Under the influence of general hyperthermia on experimental animals without a tumor, there was a decrease in the number of immunocompetent cells on the 1st day of the post-heating period with restoration by the 3rd day. Further, the number of CD3, CD4, CD20 lymphocytes continued to increase. CD8 lymphocyte count remained within the control values.
3. With a combination of general hyperthermia and the tumor process in experimental animals, against the background of a temporary increase in CD3, CD4 (3 days), a decrease in the number of immunocompetent cells (CD3, CD4, CD20 ) was noted on the 14th day of the post-heating period.
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UDC: 616.613-003.7-0898.878
EVALUATION OF THE EFFECTIVENESS OF ABSOLUTELY DRAINLESS PERCUTANEOUS NEPHROLITHOTRIPSY
F.Yu. Yuldashev1, F.R. Nasirovl, J.Kh. Mirkhamidov1 'Tashkent Medical Academy, Tashkent, Uzbekistan
Abstract
The presence of drains in the urinary tract, installed in percutaneous nephrolithotripsy, is fraught with a number of complications and causes inconvenience for the patient. Absolutely drainless percutaneous nephrolithotripsy can significantly reduce the incidence of catheter-associated urinary tract infection, reduce the need for analgesics in the postoperative period, and reduce the length of hospital stay and the cost of medical services.
Key words: urolithiasis, endoscopic treatment, complications.
АБСОЛЮТТУК ДРЕНИРСИЗ ПЕРКУТУРАЛЫК НЕФРОЛИТОТРИПСИЯНЫН НАТЫЙЖАЛУУЛУГУН
БААЛОО
Ф.Ю. Юлдашев1, Ф.Р. Насиров1, Дж.Х. Мирхамидов1 'Ташкент медициналык академия, Ташкент, Узбекистан
Аннотация
Заара чыгаруу жолдорунда тери астындагы нефролитотрипсия менен орнотулган дренаждардын болушу бир катар татаалдашуулар менен коштолуп, бейтапка ьщгайсыздык жаратат. Терссиз дренажсыз перфетитотрипсия катетер менен байланышкан заара жолунун инфекциясын азайтууга, операциядан кийинки мезгилде анальгетиктерге болгон муктаждыкты азайтууга жана ооруканада болуу узактыгын жана медициналык кызматтардын баасын томендотууго мумкундук берет.
Ачкыч сездвр: уролития, эндоскопиялык дарылоо, оорулар.
ОЦЕНКА ЭФФЕКТИВНОСТИ АБСОЛЮТНО БЕЗДРЕНАЖНОЙ ПЕРКУТАННОЙ НЕФРОЛИТОТРИПСИИ
Ф.Ю. Юлдашев1, Ф.Р. Насиров1, Дж.Х. Мирхамидов1 Ташкентская медицинская академия, Ташкент, Узбекистан
Address for Correspondence: Yuldashev Faizulla Yuldashevich, Doctor of Medical Sciences, Professor of the Department of Surgery of the Fergana Branch of the Tashkent Medical Academy. Tel. (+99890) 272-00-87.
