Visnyk of Dnipropetrovsk University. Biology, medicine

93-96

Authors: V. L. Sokolenko, S. V. Sokolenko

The objective of this research is to assess the relation of radioactive contamination degree to immune system functioning, in the absence or presence of additional potential immunosuppressants. To achieve the objective, during the period of 1995–2015 we examined 250 people, students of Cherkasy State University, who lived in the areas of enhanced radiation monitoring before. Also we evaluated the additional impact of the emotional stress caused by examinations on examined students. Indicators of cellular immunity were determined by immunophenotyping and dyeing using Romanowsky-Giemsa method. The level of immunoglobulins in blood serum was determined by radial immunodiffusion (Mancini method). The level of cortisol in blood serum was determined by immunoenzyme method. We have found that in absence of the emotional stress among residents of the areas contaminated with radionuclides, cortisol level remained at the upper limit of homeostatic norm. There is an average positive correlation between the activity of radionuclides in the territories of residence and the level of cortisol. There are marked average positive correlations between the activity of radionuclides and the level of neutrophils, and low positive correlations with the levels of IgG and IgM in blood serum. Average negative correlations between the activity of radionuclides and the following parameters are also observed: absolute and relative number of functionally mature T-lymphocytes with phenotype CD3+, absolute and relative number of their helper subpopulation CD4+, absolute and relative number of natural killer cells with phenotype CD16+; and strong negative correlations with immunoregulatory index CD4+/CD8+. Cortisol level shows the similar correlation with the same parameters, but correlation coefficient is lower. Under conditions of additional stress, caused by emotional load during the examinations, cortisol level significantly increases. This enhanced previously discovered correlations and revealed new ones: average negative correlations between radionuclide activity / cortisol level and expression of pan-T cell marker CD5, medium positive correlations with absolute and relative number of suppressor T-lymphocytes with phenotype CD8+, correlation with the level of serum IgG changes from positive to negative. Additional short-term stress factor combined with chronic influence of low doses of radiation increases the dependence of immunosuppression, caused by radiation contamination of the areas where examined students live, and causes failures in the work of compensatory mechanisms, particularly at the level of serum immunoglobulin products.

103-107

Authors: H. N. Shiyntum, G. A. Ushakovа

Cadmiumclassified as a major carcinogen is considered a poisonous and unwanted heavy metal to a lot of tissues in many organisms. Of many publications already available, the general consensus is that the cadmium attenuating element is metallothionein (MT) through its interchangeable mechanism with Zn triggered by the presence of Cd, providing binding sites for Cd ions. MT was first discovered in the kidney cortex of the horse; it represents a low molecular weight protein, rich in cysteine residues which effectively bind with metals. Its functions consist in detoxification of heavy metals like mercury, arsenic, cadmium, homeostasis of essential metals including copper and zinc, anti-oxidation against reactive oxygen species, protection against DNA damage, oxidative stress, cell survival, angiogenesis, apoptosis, and increase of proliferation. In this work, we sought to highlight the protective function of MT in the brain and serum of rats by means of detoxification under induced effects of controlled Cd doses. We have done this by exposing Wistar rats to Cd at different doses in drinking water at different time intervals. In two independent experiments, 58 rats were subjected to 0.1 or 1.0 µg Cd2+/kg of body weight for 15 or 36 days under different conditions. The obtained data indicates the different functioning systems for the brain and the blood for MT metabolism under Cd effect. Our results indicate significant loss of metallothionein level in the brain and important increases in the amount of MT in serum proving that even minimal ingestion of toxic Cd is enough to trigger the release of MT protein in blood.

113-118

Authors: I. V. Prischepa, O. G. Prokushenkova, V. S. Nedzvetsky

Reactivation of glial cells, induced by metabolic disorders of glucose utilization and development of oxidative stress in retina under diabetes mellitus, is the key pathogenetic factor of diabetic retinopathy. Nanoparticles of C60 fullerene and some of their water-soluble derivates are known as one of the strongest antioxidants having neuroprotective effect in a number of pathologies and harmful influences. In the present study, for the first time, the effects of nanostructures of hydrated C60 fullerene (C60HyFn) on the expression and polypeptide composition of glial fibrillary acidic protein (GFAP) in retina of rats with streptozotocin (STZ)-induced diabetes have been evaluated. Using immunoblotting, 1.93-fold up-regulation of GFAP in diabetic rat retina as compared with control was shown, as a result of retinal glial cells reactivation induced by hyperglycemia. Increase in GFAP-immunolabeling associated with the reactive gliosis development in retina of diabetic rats was also confirmed by immuno-histochemical method. Consumption of C60HyFn solution (90 nM) as drinking water by diabetic rats for 12 weeks caused 1.51-fold decrease of GFAP level compared to untreated diabetic animals. In addition, C60HyFn caused statistically significant lowering of glycosylated hemoglobin concentration in blood serum of STZ-diabetic rats 1.58-fold. However, nanoparticles C60 did not affect neither insulin nor glucose levels in blood of diabetic rats. In conclusion, results obtained indicate that protective action of hydrated fullerene in the initial period of diabetic retinopathy of aged animals is realized through suppression of excessive activation of GFAP-positive retinal cells.

125-132

Authors: L. V. Altukhova, K. V. Kot, Y. G. Kot, K. S. Morozova, Y. E. Persky

Mechanisms of influence of volumetric autotransplantation of fibroblasts and of the mixture of fibroblasts and keratinocytes on the development of the local 3rd degree X-ray burn and the radiation skin ulcer in guinea pigs were investigated. We used deepadministration into the irradiation zone on its perimeter of 6 doses, which contained (150–160)×103 fibroblasts and (130–140)×103 keratinocytes in 100 µl. It is shown that this autotransplantation carried out 1 hour after the irradiation, and then every 24 hours, reduces the area of burn on the 35th day, compared to the control by 63%. Radiation ulcer appears on the 10th day after irradiation and is completely healed on the 25th day. With the same regimen of administration of only fibroblasts containing (200–210)×103 cells in 100 µl, these parameters of treatment were equal to 31% on 4th and 35th day, respectively. It is shown that as a result of radiation in the area of burn the level of gene expression of collagen types I and III, elastin, fibronectin, vinculin, decorin, hyaluronansynthases 1, 2, 3, matrix metalloproteinases 1, 2, 3, 7, 9 and hyaluronidase is reduced. Besides, in the burn area the level of gene expression of transforming growth factor α, fibroblast growth factors 1, 2, 8 and anti-inflammatory cytokines – interleukin 10 and transforming growth factor-β1 – is reduced, while the level of gene expression of proinflammatory cytokine (interleykin1β) increases. Both types of autotransplantation cause the growth of the expression level of all the structural genes and regulatory proteins of biopolymers and decrease in the expression level of interleukin 1β, which leads to activation of tissue regeneration and healing of the burn wound. Reasonsfor the higher efficiency of autotransplantation using the mixture of fibroblasts and keratinocytes compared to autotransplantation by fibroblasts only are both the larger total number of live cells regularly replacing dead cells in the burn area, and mutual stimulation of auto-fibroblasts and auto-keratinocytes to proliferate and to synthesize biologically active substances, i.e. cytokines and growth factors.

141-145

Authors: G. S. Maslak

Tumor growth progression of blood cells occurs due to changes in their genetic apparatus, which affects not only the cells morphological characteristics, but also their functional activity which to a greater extent depends on the membrane surface structures, a significant part of which is of glycoprotein nature. Complex type N-glycans are components of surface glycoproteins in the most of leukocytes. Thus, the study of changes in carbohydrate determinants of glycoproteins on the surface of leucocytes in tumorigenesis can help to reveal the mechanisms of this process. The aim of our study was to investigate the monocytes and granulocytes cytoplasmic membrane N-glycosylation in patients with chronic leukemia. The object of the study were blood cells of patients with chronic lymphocytic leukemia (n = 12) and polycythemia vera (n = 15) aged 58–66 years. Healthy hematologic volunteers (n = 15) aged 55 to 65 years were in the control group. N-glycan exposure on monocytes and granulocytes was investigated by flow cytometer Beckman Сoulter EPICS with Canavalia ensiformis lectin – Con A conjugated with fluorescent labels. The number of dead cells was monitored by means of binding them with propidium iodide. The result has been analyzed with FC Express. According to our data, levels of ConA-positive monocytes and granulocytes were 9,9 ± 1,0% and 32,7 ± 3,2%, respectively, in peripheral blood of healthy persons. The level of ConA-positive monocytes decreased to 31,0 ± 2,3% and the number of ConA-binding granulocytes increased to 66,7 ± 3,8% in patients with chronic lymphocytic leukemia compared with the norm. The number of ConA-positive monocytes decreased 3.3 times, and the level of granulocytes interacting with Canavalia ensiformis lectin slightly increased relative to control in polycythemia vera patients. There is significant increase in Con A-positive epitopes on granulocytes in patients with chronic lymphocytic leukemia and polycythemia vera compared with the control group, and absence of any difference in Con A-positive epitopes on monocytes. 100 times increase of the number of ConA-binding glycotopes is observed on the surface of granulocytes in peripheral blood of patients with polycythemia vera, and 3,3 times increase in patients with chronic lymphocytic leukemia, which may serve as an additional marker for the diagnosing these diseases.

151-155

Authors: D. Z. Vorobets

Methods of estimation of effectiveness of the open and laparoscopic pyeloplasty, as well as endo-urological palliative methods – laser resection, balloon dilatation and endopyelotomy, which determine the anatomical and functional peculiarities of renal pelvis and pyelo-ureteral junction with the help of ultrasound diagnostics during the forced diuresis, have been proposed. Changes of the area of renal pelvis, the velocity of post-furosemide increase of the scope of renal pelvis, rate of its drainage, changes in the diameter of pyeloureteral junction have been studied. This methodical approach is non-invasive, informative and simple in application. It is shown that dispersions of samples of patients after the open surgery do not differ from the dispersions of samples of the same patients before the operation on such parameters as areas of renal pelvis before the induction of furosemide, areas of renal pelvis after 15 minutes administration of furosemide, the rate of drainage after furosemide, the original diameter of pyeloureteral junction. This may indicate the stability of surgery results. For example, the larger renal pelvis by kidney size before the operation corresponded to the larger designed pelvis after the operation; renal pelvis drained faster before the operation, features faster drainage after the operation as well. Variation in the areas of renal pelvis which decreased in 40 minutes after furosemide, percent rate of longitudinal pelvis area, rate of after-furosemide increase in pelvis area, diameter of pyeloureteral junction in 15 minutes administration of furosemide after the open pyeloplasty was significantly different compared to the variation in the same parameter for the same patients before the operations. More substantial difference was observed in the same patients before and after Anderson-Hynes surgery by parameters of relative rate of after-furosemide drainage of pelvis and increase in diameter of pyeloureteral junction after 15 min administration of furosemide. That is, the same principle of operation provides similar results by anatomical parameters, such as size and diameter of pyeloureteral junction, but quite different results by functional parameters which reflect the possibility of draining of kidney in forced diuresis. Successful open pyeloplasty leads to a significant decrease in the pelvis area at different time intervals after furosemide administration, the relative increase in the pelvis area on the background of the induction of diuresis, rate of pelvis drainage, increase (normalization) in diameter of pyeloureteral junction, including the larger (better) gap of pyeloureteral junction after administration of diuretic. Concerning laparoscopic pyeloplasty, the dispersion of mean values of S, SPR, Vpr, V, VOT, D, DD after the operation was significantly different from those before the operation. This means that as in the case with open surgery, satisfactory clinical results such as reduction in renal pelvis and restoring the passage of urine through sufficient diameter pyeloureteral junction after laparoscopic pyeloplasty lead nevertheless to significant differences in the digital parameters during the objectification of operation effect by means of diuretic ultrasonography using furosemide-induced diuresis. Endoscopic surgery such as laser resection, endopyelotomy and balloon dilatation stably provides similar results (equal variances) by such parameters as pelvis area, which decreases in 40 min after furosemide administration, formation of the wide enough diameter of pyeloureteral junction and its minor fluctuations with the diuretic load. The decrease to normal parameters of all planes of renal pelvis (both before and after loading) and significant improvement of pelvis drainage (parameters responsible for the functional state of kidneys and pyeloureteral junction) indicate the success of palliative surgery in elimination of the narrowing of pyeloureteral junction.

161-164

Authors: Y. G. Kot, E. V. Kot, E. S. Morosova, E. E. Persky, M. A. Gritsenko, N. I. Bulankina

We studied gene expression of five metallothioneins (MT 1-5), ubiquitin and protein p53 and their products in fibroblasts culture of the skin and lungs of white rats of different ages (2 weeks, 1, 3, and 24 months) and determined its (metallothionein 1-5 types, ubiquitin, p53) product quantity. All these proteins are protective ones, but perform their functions by using different mechanisms. Metallothionein bind, transport and excrete ions of bivalent metals, ubiquitin controls the cleavage of the defective and short-lived proteins in the proteasome, protein p53 controls apoptosis, thus ensuring the genome stability. The similarity of age dynamics of gene expression of ubiquitin and MT of cells of both sources has been shown – maximum at 3 months. Expression of p53 gene has a difference: both in the skin and lungs expression increases up to 24 months. Product quantity of p53 has a minimum in the skin at 3 months and remains constant; in the lungs, this value has a maximum at 1 month.

9-16

Authors: S. L. Popel, B. M. Mitckan, S. Z. Krasnopolsky, I. V. Melnik

The purpose of this paper is to study the morphological changes of neurocytes in spinal cord of rats in hypokinesia and subsequent physical loading. Studies were performed on 55 laboratory rats of Wistar line. Materials of the research were the anterior horns of the gray matter of L5-S2 spinal segments. Preparations stained by Nissl and Viktorov were examined histologically. Hypokinesia was modeled following on the author’s technique. It was established that during prolonged hypokinesia in neurocytes of spinal cord of rats morphological changes in cell size and shape of the motor nuclei of all segments under study have been recorded. The number of hypochromic, hyperchromic destructively unchanged and hyperchromic destructively altered neurocytes increase; shadow cells appears, as well as cases of satellitosis and neuronophagia. Decrease in of albumen synthetical neurocyte function has been recorded. Physical loading of the average aerobic capacity leads to normalization of structural and functional state of neurocytes and enhances the reparative processes, as evidenced by a number of positive changes in morphometric parameters: increase in the number of normochromic neurocytes and decreasing the number of hyper- and hypochromic neurocytes with destructive signs, absence of pyknotic forms. Morphological parameters of neurocytes and their nuclei after physical loading of average aerobic capacity do not differ from those in the control group of intact animals. In neurocytes of this group of rats RNA concentration increases by 12.6% compared to animals after prolonged hypokinesia. Neurocytes of spinal cord of rats after prolonged hypokinesia develop significant morphological changes which are characterized by emergence of a significant number of hyperchromic neurocytes with signs of destructive changes and shadow cells, as well as and hypochromic neurocytes with signs of destructive changes, reduction in size and change of shape of perikaryons of neurocytes and their nuclei. Morphological changes of neurocytes after prolonged hypokinesia are accompanied by violations of biosynthetic processes, as evidenced by RNA decrease in the cytoplasm of efferent neurocytes of spinal cord of rats. Physical loading of average aerobic capacity leads to normalization of structural and functional state of neurocytes and promotes the reparative processes suported by positive changes in morphometric parameters.

23-27

Authors: O. V. Kulibaba, S. M. Kozishkurt, O. O. Duzenko, I. L. Vovchuk, S. A. Petrov

The paper presents the results of determining the amount of reduced glutathione, glutathione reductase and glutathione peroxidase activity at transplantation of muscle tissue taken from rats from the same litter. During the work 2 surgical interventions were carried out: transplantation of muscle tissue taken from the same litter of rats, and operation without replanting. Transplantation was performed on nonlinear white male rats weighing 180–300 g. The animals were taken out of the experiment by passing electric current through the medulla oblongata. For donor transplants males from the same litter were used. In adult donor rats abdominal muscle tissue was extracted and transplanted to homologous tissue of the recipient rat. The same procedure was carried out with femoral muscle tissue. Operation without replanting was used to compare the effects of changes in the number of investigated parameters of the surgical exposure. Tissue not subject to any surgery served as a control. Parameters under study were determined on the first, third and seventh day after transplantation. Glutathione levels in tissues were determined byE. Butler, A. Dyubona, B. Kelly. Determination of glutathione reductase is based on the reduction of NADPH registration. Glutathione peroxidase activity was determined by accumulation of oxidized glutathione. Surgery is known to lead to expression of oxidative stress in the organs operated. Special role in antioxidant protection of the body is given to thiols. Expressed hydrophilic properties provide their high content in water fraction of cells and ability to protect biologically important molecules (enzymes, nucleic acids, hemoglobin) from oxidative damage. Property of thiol compounds is known to inhibit both fermented and not fermented free radical oxidation. For the first time it was found that transplantation of muscle tissue taken from animals from the same litter lead to significant reduction of glutathione in the femoral muscle of the recipient and abdominal muscle tissue of the donor and recipient and to significant increase in glutathione reductase activity in the femoral muscle tissue of the donor and in the abdominal muscle tissue of the donor and recipient.

32-35

Authors: O. Y. Galkin, Y. V. Gorshunov, V. F. Solovjova

To address a number of fundamental and applied problems in immunology, molecular and cellular biology and biotechnology it is necessary to obtain Fc-fragments of immunoglobulins. Fc-fragments may be used for studying of the effector functions of antibodies which are mediated by these areas. They are often used as an immunogen to produce anti-specie (based on so-called secondary antibody) conjugate in the development of serological tests for diagnostics (predominantly such conjugate based on monoclonal antibodies). The work is aimed to develop improved methods of obtaining and allocation of Fc-fragments of human IgA. To achieve this objective, optimization of hydrolysis of IgA with subsequent purification of Fс-fragments have been carried out. Improved method of obtaining Fc-fragments of IgA provides: papain hydrolysis of immunoglobulin in the environment of nitrogen for 4 h, allowing to achieve maximum output of Fc-fragments without their further degradation: isolation and purification of Fc-fragments of human IgA by one-stage gel filtration on sephadex G-100; control of purity of the target product by electrophoresis in polyacrylamide gel with sodium dodecyl sulfate and Ouchterlony immunodiffusion. Enzymatic hydrolysis was carried out at the optimal temperature of papain (37 °C). As the oxygen in the air may have inhibitory effect on enzymatic hydrolysis reaction, the reaction mixture was incubated in the nitrogen atmosphere to prevent inactivation of papain. To reduce the incident degradation of immunoglobulin molecules, papain hydrolysis was carried out without using an enzyme activator (cysteine). Usage of the proposed scheme allows obtaining Fc-fragments of human IgA of high purity. Outcome of Fc-fragments after all stages of purification was about 18% of the initial amount of IgA in the preparation. Molecular weight from Fc-fragments of human IgA was equal to approximately 70 kDa.

40-44

Authors: G. І. Zvir, O. М. Moroz, S. O. Hnatush

Objects of the study were sulfate-reducing bacteria Desulfovibrio desulfuricans ІМV К-6, isolated from Yavorivske lakе. This strain is kept in the collection of microorganisms at the Department of Microbiology of Ivan Franko National University. Bacteria were grown in the Kravtsov-Sorokin’s liquid medium with the following composition (g/l): Na2SO4 × 10H2O – 0.5, NaH2PO4 – 0.3, K2HPO4 – 0.5, (NH4)2SO4 – 0.2, MgSO4 × 7H2O – 0.1, C3H5O3Na – 2.0. The bacteria were grown for 10 days at 30 °C under anaerobic conditions. In order to study the sensitivity of the sulfate reducing bacteria to action of Uragan and Raundup herbicides, the cells of D. desulfuricans ІМV К-6 were grown at the concentrations of herbicides as follows: 0,28 mМ, 2,8 mМ (concentration recommended for use) and 5,6 mM. Biomass was determined by photometric method. Concentration of hydrogen sulfide in the culture medium was determined by photo-colorimetric method. Concentration of sulfate-ions in the medium was determined by turbidimetric method. Capacity of sulfate reducing bacteria D. desulfuricans ІМV K-6 to grow, reducing sulfates to hydrogen sulfide upon influence of Uragan and Raundup herbicides was studied. Accumulation of bacterial biomass in the control and upon influence of herbicides was the highest on the fourth-sixth day of cultivation, and after that the stationary growth phase began. It was shown that sulfate reducing bacteria upon influence of herbicides grew more intensively compared with the control. It was discovered that the level of biomass changed depending on the increasing concentration of Uragan or Raundup herbicides in the medium. Sulfate reducing bacteria D. desulfuricans ІМV K-6 could reduce sulfates to hydrogen sulfide in the presence of sulfates and organic compounds in the medium (dissimilatory sulfate reduction). Stimulatory influence of Uragan and Raundup on the dissimilatory sulfate reduction process of D. desulfuricans ІМВ К-6 has been discovered. The formation of hydrogen sulfide correlates with the usage of sulfatе ions. The capacity of sulfate reducing bacteria D. desulfuricans ІМV K-6 to grow, reducing sulfate ions to hydrogen sulfide upon influence of Uragan and Raundup may be caused by presence of inert components (sulfates) in these herbicides that can be used by microorganisms as electron acceptors during sulfate respiration.

51-56

Authors: I. U. Pismenetskaya, T. D. Butters

Free oligosaccharides (FOS) are unbound structural analogs of glycans of glycoconjugates. There are several sources of them inside the cell: 1) multistep pathways of N-glycosylation, 2) the cell quality control and endoplastic reticulum-associated degradation of mis-glycosylated and/or misfolded glycoproteins, 3) lysosomal degradation of mature glycoconjugates. Some of these FOS are the earliest indicators of potential glycosylation alterations that would be revealed in the course of the cell quality control and the endoplastic reticulum-associated degradation. Ischemia and hypertension cause stress of intracellular organelles leading to disruption of their functions. The main objective of the work was the characterization of free oligosaccharides (FOS) in plasma obtained from patients with cardiovascular diseases compared to those from healthy subjects to evaluate the potential of these compounds for diagnostics. Chromatographic profiles of FOS composed of 4–12 monosaccharides were obtained and analyzed for quantitative and qualitative differences between the samples. After plasma deproteinization and FOS purification the oligosaccharides were labelled with anthranilic acid (2-AA), separated into the neutral and charged with QAE Sephadex (Q25-120) chromatography and analysed using high-performance liquid chromatography (HPLC). Glucose unit values were determined following comparison with a 2-AA-labelled glucose oligomer ladder derived from a partial hydrolysate of dextran as an external standard. The data were collected and processed using Empower software. The charged FOS were digested with the sialidase from Arthrobacter ureafaciens. 2-AA – labelled free oligosaccharides from transferrin were used as an external standard for the structure decoding. The profiles obtained were compared with intracellular free oligosaccharides of known structures and with the glycan structures and their descriptions in the databases GlycoBase and EUROCarbDB. These approaches allowed predicting a range of glycan structures for each of the main peaks of HPLC profiles of plasma free oligosaccharides and managing ways for their future experimental analysis. In the case of cardiovascular disorders, HPLC profiles of FOS revealed a changing pattern of heterogeneity, depending on the severity of the disease. Three main enlarged glycan species in the netral fraction and one peak in the charged fraction distinguished the FOS of the patients from those of the healthy volunteers. It has been revealed that the neutral marker peaks were represented by polimannose glycans with 5–7 mannose residues and 1–2 residues of N-acetylglucosamine, and one of the major peaks of the charged fraction – by two-antennary complex N-glycan with two sialic acid residues. The study of free oligosaccharides of blood plasma is a new field of glycobiology allowing an evaluation of an organism state at the level of the cell organelle functional status and openning up broad prospects for finding early diagnostic and prognostic markers of cardiac insufficiency.

63-67

Authors: O. E. Shaul’ska, L. M. Diachenko, T. P. Nikolayenko-Kamyshova, A. I. Shevtsova

Destruction of malignant cell clones and search for markers of the effectiveness of chemotherapy in patients with hematologic malignancies is an urgent direction of research. The purpose of this paper was to study plasma of patients with various forms of blood tumor, the activity of trypsin-like enzymes, matrix metalloproteinases MMP2 and MMP9, content of α1-proteinase inhibitor and α2-macroglobulin before and after the cytotoxic therapy by anthracycline antibiotics, doxorubicin and daunorubicin. It was established that concentration of inhibitors and activity of trypsin-like enzymes increased in patients with acute myeloid leukemia and multiple myeloma against the backdrop of multidirectional changes of proMMP9. Activity of the latter enzyme was reduced to 0,03±0,01 rel. u. in acute myeloid leukemia, and after chemotherapy it increased 7 times. Reducing level of inhibitors and increasing activity of MMP9 were found in chronic lymphocytic leukemia. The presence of the correlation between the α2-macroglobulin and gelatinase activity in the treatment indicates that the inhibitor is an important mechanism for storing of gelatinоlytic potential. Balance between proteolysis and antiproteolysis depends on the type of proliferating cells and the course of the disease. Indicators of tissue destruction may be an additional criterion for monitoring the stage of blood tumors and efficacy of treatment.