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Background. Mastocytosis is a rare myeloproliferative disease based on clonal hematopoiesis of mast cells, with accumulation of mast cells in various tissues and organs. The cutaneous mastocytosis is common in the pediatric population and, in general, progression to aggressive forms is not typical. In the adult population, there is systemic mastocytosis with a predominance of indolent and smoldering forms according to the literature, but there aren’t epidemiological data for the Russian Federation.Aim. To evaluate the results of primary diagnostics obtained during the examination of 70 patients with suspected systemic mastocytosis.Materials and methods. The histological studies of the skin and bone marrow, mutations in the c-kit gene in the bone marrow and serum tryptase level were examined in the Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation in accordance with WHO 2017 criteria.Results. The diagnostic results of 70 patients with suspected mastocytosis, the diagnosis was confirmed in 71.4 % (n = 50) of patients, of which systemic mastocytosis accounted for 82 % (n = 41). The 2 most common categories were identified: indolent systemic mastocytosis in 23 (56 %) patients and widespread forms in 15 (36.5 %), with a median time of diagnosis of 12 and 5 years, respectively.Conclusion. The late diagnosis is noted in all subgroups of systemic mastocytosis.

The key problem of introducing nanoparticles into clinical practice for diagnostic and therapeutic purposes is their safety. Connective tissue, an important component of which are mast cells, reacts actively in response to foreign particles. The reaction of mast cells can be an indicator of the biocompatibility of foreign particles. The study was conducted on male Wistar rats. Iron-carbon nanoparticles in the FeC modification stabilized in an aqueous medium using an auxiliary substance were used. Tissue examination (liver, lungs, heart, thymus, kidneys) was performed 1, 7 and 30 days after injection. After the injection of nanoparticles, the largest quantity of them is found in the liver and lungs, a smaller quantity is found in the heart, kidneys and thymus. The liver and lungs are the main organs of excretion of nanoparticles due to phagocytes. The accumulation of nanoparticles in the liver leads to the development of destructive processes and to the activation of compensatory and adaptive mechanisms in the form of cellular and intracellular regeneration of hepatocytes. In organs with a low content of nanoparticles, structural changes are poorly expressed. The mast cells of the studied organs react differently to the introduction of nanoparticles. The first to react are the mast cells of the liver by reducing the quantity and increasing degranulation. The population of lung mast cells reacts unidirectionally by sharply activating degranulation without changing the amount. An increase in the secretory activity of mast cells in the lungs and liver indicates the participation of mast cells in the regulation of particle elimination through intercellular signaling pathways of interaction with the system of phagocytic mononuclear cells. Heart mast cells are involved in maintaining the inflammatory process in the early period of the experiment, contribute to the return of myocardial parameters to homeostatic norm in the late period of the experiment. Mast cells can be considered as indicators of biocompatibility nanoparticles. The absence of an inflammatory process and the preservation of the structural and functional characteristics of the tissues where nanoparticles accumulate, as well as the reaction of mast cells in them, indicate the relative safety of the particles under study.

During the pandemic of the new coronavirus infection COVID-19 the question about the importance of mast cells and their proteases arose. The aim of this study is to determine the role of mast cells and their proteases chymase and tryptase in the pathogenesis of severe COVID-19. Materials and methods. The study included 55 patients: 29 male (52,7 %) and 26 female (47,3 %) aged 67 [62;71] years with severe COVID-19 and fatal outcome. An analysis of postmortem lung biopsies of patients with COVID-19 was carried out, determining the representation of mast cells, protease profile and degranulation activity. A correlation analysis was carried out between mast cell and clinical and laboratory parameters of patients. Results. Increased number of mast cells and their degranulation activity were found in patients with chronic heart failure, obesity, chronic kidney disease, coronary heart disease and acute cerebrovascular accident. Degranulation of tryptase-positive mast cells are depleted as the duration of the disease increases: the content of single tryptase-positive mast cells (%) negatively correlates with the duration of the disease and hospitalization (p = 0,015, r = -0,327 and p = 0,006, r = -0,368, respectively), the content of tryptase-positive mast cells fragments (%)correlates with the duration of hospitalization (p = 0,007, r = 0,357). Correlations were established between the levels of non-conjugated bilirubin and alanine aminotransferase with the content of single tryptase-positive mast cells (per mm2) (r = 0,340, p < 0,05 and r = 0,307, p < 0,05, respectively), as well as single degranulated tryptase-positive mast cells (per mm2) (r = 0,369, p < 0,05 and r = 0,363, p < 0,01, respectively), and the level of conjugated bilirubin with the content of single tryptase-positive mast cells (%) (r = 0,415, p < 0,05). The blood calcium level correlates with the absolute total content of single tryptase-positive mast cells (p = 0,013, r = 0,457), as well as degranulated (p = 0,017, r = 0,441). A negative correlation was also found between potassium level and the relative content of single non-degranulated tryptase-positive mast cells (p = 0,014, r = -0,352). Correlations were found between the level of total bilirubin at the time of admission and over time with the content of single degranulated chymase-positive mast cells (per mm2) (p = 0,043, r = 0,277 and p = 0,027, r = 0,317, respectively). Urea level upon admission positively correlates with the absolute total content of single chymase-positive mast cells (p = 0,045, r = 0,277), as well as degranulated (p = 0,04, r = 0,283). The potassium level in the blood correlates with the total content of co-adjacent chymase-positive mast cells (p < 0,05, r = 0,388), as well as content of co-adjacent degranulated chymase-positive mast cells (p < 0,05, r = 0,388). Conclusion. Significant correlations were noted between mast cells parameters and duration of the disease and hospitalization, the presence of comorbidities, unconjugated and conjugated bilirubin, ALT, urea, total protein, sodium, potassium and calcium blood levels. An increase in the number of mast cells and their degranulation activity has been found in patients with comorbidities: chronic heart failure, obesity, chronic kidney disease, ischemic heart disease and previous stroke. The revealed depletion of degranulation processes of tryptase-positive mast cells as the duration of the disease increases indicates their role in lung damage. We noted participation of mast cells and their proteases chymase and tryptase in the development of liver and kidney damage in patients with COVID-19, which confirms their importance in the severe course of the disease and may be considered in the future for the development of pathogenetic therapy.

Introduction: Mastocytosis is a rare hematologic neoplasm characterized by the abnormal proliferation and accumulation of mast cells in various tissues. Its clinical manifestations vary widely, ranging from cutaneous lesions to systemic involvement with potentially life-threatening symptoms. Understanding the pathophysiology, diagnosis, and management of mastocytosis is crucial for improving patient outcomes. Aim of the Study: The aim of this study was to provide a comprehensive overview of mastocytosis, including its epidemiology, risk factors, pathophysiology, clinical manifestations, diagnostic approaches, and management strategies. By synthesizing current knowledge on mastocytosis, this study aims to enhance understanding of the disease and guide clinical practice. Description of the State of Knowledge: Mastocytosis is classified into cutaneous and systemic forms, with various subtypes based on clinical and histopathological features. Diagnosis relies on a combination of clinical suspicion, serum tryptase levels, histological examination of bone marrow biopsies, and genetic testing. Management strategies include symptomatic treatment, avoidance of triggers, and targeted therapies such as monoclonal antibodies and tyrosine kinase inhibitors. Advanced forms may require cytoreductive therapy or allogeneic hematopoietic stem cell transplantation (alloHSCT). Conclusions: Despite advancements in diagnosis and treatment, achieving lasting remission in mastocytosis remains challenging, especially in advanced cases. Further research into the molecular mechanisms underlying the disease and the development of novel therapeutic modalities are needed to improve patient outcomes and quality of life.

Mast Cell Activation Syndrome (MCAS) is a severe relapsing disease requiring inpatient treatment, with clinical pattern including the features of anaphylaxis. The article presents diagnostic criteria aimed for differentiation of MCAS from similar severe conditions as well as discusses local forms of mast cell activation. The consensus group has established distinct criteria for diagnosing MCAS. The agreed criteria include episodic (recurrent) occurrence of typical systemic symptoms caused by release of mast cell mediators and involve, at least, two organs; an increase in serum tryptase level by, at least, 20% over individual baseline tryptase plus 2 ng/mL tryptase during 3-4 hours of the pathological reaction; a positive response to drugs that either target mast cells mediators, or their effects. In principle, the classification of MCAS is based on its etiology being subdivided into primary (clonal) MCAS, secondary MCAS, and idiopathic MCAS. The primary MCAS is determined by clonal expansion of mast cells and is considered systemic mastocytosis. In secondary MCAS, normal mast cells are activated by the known triggers, e.g., IgE. If neither clonal expansion nor a trigger for mast cells activation are identified, the condition is defined as idiopathic MCAS.The new COVID-19 infection has attracted particular interest in MCAS, since the severe course of COVID-19 was thought to develop due to latent MCAS, but the criteria for MCAS in these patients were not reproduced. In the presence of local symptoms, such as urticaria, or in cases of single-organ involvement, e.g., isolated gastrointestinal symptoms, and suspected mast cell activation being basic to pathogenesis, the term mast cell activation disorder was introduced. Moreover, the article discusses several different mediators that are proposed as markers in the diagnosis of MCAS.However, over-diagnosis of MCAS entails the risk of missing the underlying pathology, which is not associated with MCAS, and requires differential diagnosis with a number of diseases. In the absence of severe attacks (with hypotension and shock), the likelihood of MCAS is generally very low. Of course, the patients with mastocytosis and/or confirmed IgE-dependent allergy are at higher risk of developing MCAS, but a key diagnostic marker is an event-related increase in mast cells tryptase from baseline determined over the asymptomatic period. The diagnosis of MCAS is highly likely if the tryptase level rises above a certain threshold (20% of baseline plus 2 ng/mL).

The study purpose. Identification of structural and functional changes in pelvic lymph nodes in experimental metastatic prostate cancer.Materials and methods. The study included 30 male mice aged 3 months. All animals (n = 30) were divided into 2 groups. The first group (the main one, n = 20) included mice that had a model of metastatic prostate cancer created by transplanting an Ehrlich tumor into the prostate parenchyma. These animals were further divided into two equal subgroups: 1a (n = 10) – mice were withdrawn from the experiment on day 7; 1b (n = 10) – mice were withdrawn from the experiment on day 18. The second group (n = 10) included mice that were not manipulated, they made up the control group. After the end of the experiment, morphological analysis of the prostate gland and regional (pelvic) lymph nodes in mice of both groups was performed using light microscopy. Statistical processing of the results was carried out using the Statistica 8.0 software package. The differences were considered statistically significant at p < 0.05.Results. When compared to the control group the mice of groups 1a and 1b, the prostate parenchyma was almost completely replaced by atypical cells, which demonstrates the presence of neoplastic processes in the prostate gland. In group 1a mice, the number of pelvic lymph nodes was 1.9 times as large, and in group 1b animals, this indicator was 2.7 times higher compared to the second group (p < 0.01). In animals of the first group, the proportion of mast cells in the pelvic lymph nodes increased by 121 % compared to the control group (p < 0.01). At the same time, we revealed a direct relationship of mast cells with the number of tumor cells and immunoblasts in the medullar sinuses, which indicates the participation of tissue basophils in tumor metastasis. We also recorded a significant increase in the area of the medullar sinuses of regional lymph nodes in animals of groups 1a by 12.4 % (p < 0.05) and 1b by 20.2 % (p < 0.01) against the background of an increase in the number of mast cells in this zone compared to the control group, which indicates the possible participation of mast cells in lymphangiogenesis.Conclusion. Mast cells can potentially play a role in the development of malignant neoplasms of the prostate gland. The number of mast cells increases in pelvic lymph nodes in animals with a created model of metastatic prostate cancer. The obtained direct dependence of the increase in the number of mast cells and the increase in the number of tumor cells with immunoblasts suggests the participation of tissue basophils in the spread of metastases. It can be assumed that infiltration of lymph nodes by mast cells may correlate with a poor prognosis of prostate cancer, since these granulocytes contribute to tumor metastasis.

Introduction World literature data indicate the involvement of mast cells in the pathogenesis of Dupuytren's disease. There is no information on the content of mast cells in the pathologically altered palmar fascia of patients depending on the severity of the contracture. Purpose To study changes in the number, location and degranulation activity of mast cells in the palmar aponeurosis with Dupuytren's contracture of varying severity. Material and methods Histopathological study of surgical material from 52 patients (49 men and 3 women) with Dupuytren's contracture (age range 35-78 years, mean age 59.12 ± 1.25 years) using histomorphometry of epoxy semi-thin sections stained with methylene blue – the main fuchsin. Patients were divided into two groups: group 1 with 1‑2 (n = 16) and group 2 with 3-4 (n = 36) grades of the contracture. Results In group 2, the location of mast cells among contractilely altered collagen fibers of dense connective tissue was recorded more often than in group 1. In group 2, compared with group 1, the following significantly increased: the median number density of mast cells – by 33.79 % (p = 0.0508), the median area of mast cells – by 48.40 % (p = 0.0008) and the index mast cell degranulation – by 94.68 % (p = 0.00000001). Discussion Along with a change in the typical location of mast cells, objective evidence of an increase in their number, activation and degranulation in patients with severe contractures was obtained. Conclusion The obtained results indicate the role of mast cells in the progression of Dupuytren's contracture and expand the understanding of potential therapeutic targets.

Mast cells (MCs) are a required component of the thymus microenvironment. They affect intercellular interactions and permeability of the hematothymic barrier through cytokine production. There is speculation that the thymus is the site of MCs formation and deposition. MCs are under complex neuro-endocrine control and they can play an important role in the process of acute transformation of the thymus in the formation of a stress reaction, affecting the extrathymic migration of cells. The purpose of this study is to assess the functional involvement of MCs in the process of the thymus acute transformation at various hyper- and hypodynamic effects during the formation of stress response and without it.The study was conducted on male Wistar rats. The stress factors were physical activity (swimming) of different intensities and immobilization, which represent two opposite states of dynamic stress. MCs were classified on histological preparations; a degranulation coefficient and a mean histochemical coefficient (synthetic activity) were calculated.In groups with preserved adrenal glands after exposure a significant decrease in the thymus mass coefficient is noted, which indicates a weakening of its functional activity in response to the development of stress. At the same time, MCs of the thymus quickly respond to neuro-endocrine factors under stress. These cells are involved in a general reaction: their activity consists in a synchronous decrease of the synthesis of granules in the cytoplasm and an increased release of active substances accumulated earlier. The mass and structure of the thymus remain unchanged in groups with removed adrenal glands after immobilization. No changes in morphofunctional indicators of mast cells were detected either. Experiments with hypo- and hyperdinamic loading of animals with preserved and removed adrenal glands indicate that the MCs response is largely determined by the hypothalamic-pituitary-adrenal axis of the endocrine system. Removal of the adrenal glands (inability to release glucocorticoids) leads to a lack of functional response from the thymus MCs. The stimulating effect of adrenal glucocorticoids on MCs under stress is carried out in combination with other neuro-endocrine factors (catecholamines, corticotropin-releasing hormone, adrenocorticotropic hormone). When this axis is activated and a full-fledged stress reaction is formed by the body, MCs are actively involved in the process of acute transformation of the thymus through cytokine secretion. These is an important condition for the development of adaptation mechanisms by the immune system.

The aim of this work was to study the antiallergic activity of Origanum vulgare herb tea on the model of mast cell degranulation in vitro. Origanum vulgare herb tea was prepared by infusion at room temperature in a ratio of plant raw material and boiling water P 1.5: 100 for 15 minutes. The resulting tea was evaporated. The dry residue contained 37.25 ± 0.95% of the total of phenolic compounds in terms of gallic acid and 2.63 ± 0.20% of the total of flavonoids in terms of cynaroside. The study was carried out on outbred male mice. The animals were kept in accordance with the established requirements. The requirements for setting up an experimental study using laboratory animals and humane treatment of them were abided by in this work. An epidermal cat hair allergen produced by “Biomed named after I.I. Mechnikov”, the Russian Federation was used to sensitize the animals. Allergenic effect was not detected in the medicine being studied on animals of the intact group and the “placebo” group. When assessing the antiallergic effect of Origanum vulgare herb tea on sensitized animals, a significant (p

The proportion of men with impaired sperm fertility is increasing every year, which is one of the factors in the decline in fertility and is becoming both a medical and social problem. Modern diagnostic methods make it possible to recognize many factors of male infertility: genetic, endocrine, infectious, extra-genital, etc. However, despite all modern biomedical advances, 1/3 of patients remain with an unrecognized cause (idiopathic) of male infertility. At the same time, we must not forget that most patients from this category do not want to resort to assisted reproductive technologies to realize paternity, and they strive to achieve pregnancy in a natural way. Therefore, the search for the causes of male infertility remains an urgent issue in modern urology field. This article reviews the literature on the role of mast cells in the formation of fibrosis in tissues, including the testis. Mast cells affect the proliferation, functioning and phenotype of fibroblasts put under hypoxic conditions. Fibroblast activation enhances collagen fibrillogenesis. Studies by Russian and foreign scientists have shown that with sperm pathology, the number of mast cells in the connective tissue of the testicle increases sharply. Against the background of an increase in the number of mast cells in the interstitium of the testis, fibrosis of the wall of the convoluted seminiferous tubules increases. Moreover, in severe spermatogenesis disorders (Sertoli cell-only syndrome, Germ cell aplasia), mast cells were found both in the peritubular space and in the lumen of the convoluted seminiferous tubules. Most infertile men have significant amounts of significant amounts of mast cells in their ejaculate. There are sporadic data on the negative correlation between the presence of mast cells in seminal plasma and the concentration and motility of spermatozoa. Conclusion. The negative effect of mast cells on spermatogenesis remains unknown to the end. Mast cells have a high ability to migrate to connective tissue, which levels increase during inflammation, and the production of many mediators, proteases and histamine, cytokines, which can be both a trigger in the formation of sperm pathology and the cause of the formation of fibrosis in the testicle.

Carboxypeptidase A3 (CPA3) is a specific protease of mast cells (MC) with variable expression and appears to be one of the preformed components of the secretome. CPA3 is involved in regulation of the state of a specifi tissue microenvironment and components of the integrative-buffer metabolic environment in adaptive and pathological processes; it affects implementation of the innate immunity, mechanisms of angiogenesis, processes of the extracellular matrix remodeling, etc. CPA3 identification using protocols of multiplex immunohistochemistry allows specifying details of the organ-specific mast cell population features, including the protease phenotype, mechanisms of biogenesis with cytoand histotopographic criteria, and features of secretory pathways. Numerous biological effects of CPA3, including participation in the regulation of the pulmonary parenchyma and systemic blood flow, in biogenesis and remodeling of the fibrous component of the extracellular matrix, in epigenetic reprogramming, determine the importance of fundamental investigation of the physiological activity of protease and its involvement in the implementation of pathological processes. Further studies will contribute to the detection of the translational value of the mast cell CPA3 expression features as a prognostic factor and a promising molecular target for treatment of socially significant diseases.

Several hypotheses regarding the pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) have been put forward, but no consensus has yet been reached. It is suggested that cytokines are involved in IC/BPS, as well as in inflammatory autoimmune diseases. Examining various biomarkers of bladder tissue, including mast cells is underway. However, few reports on a consistent immune activity profile are available. The aim of the study was to assess the cytokine profile, counts of mast cells and plasma cells as well as their relationship in patients with IC/BPS with and without Hunner’s lesions. 44 women with Hunner’s lesions (group I) and 82 women with non-ulcer type (group II) were examined. Patients were questioned on the Pelvic Pain Symptom Scale, Urinary Frequency Scale (PUF), Visual Analogue Scale (VAS) and O’Leary–Santa Interstitial Cystitis Symptom Index (ICSI). Cystoscopy and hydrodistension of the bladder were performed under general anesthesia. In biopsies of the bladder wall, the number of plasma cells and mast cells was assessed, in urine — IL-1β, IL-6, IL-8, TNFα. Statistical processing of the results was carried out using the Statistica 6 software (StatSoft, USA). The Student’s t-test, Spearman’s correlation coefficient were calculated. In patients with Hunner's ulcer, there was an insignificant increase in the scale indices and decreased magnitude for average volume, urination frequency, and maximum emptying volume. The maximum bladder capacity during hydrodistension was lowered by 42.01% (p 0.05), as well as between count of plasma cells and IL-6 level (r = –0.639, p < 0.05). In group II, a significant connection was found between count of mast cells and TNFα level (r = +0.562, p < 0.05). Patients with Hunner’s IC/BPS are characterized by severe inflammation, wherein mast cells are involved in induction. Determination of cytokines in urine can provide a non-invasive division of IC/BPS into ulcerative and non-ulcerative groups.

Neurofibromatosis type 1 (NF1) is a hereditary tumor syndrome occurring with a frequency of 1: 3000 of the population. NF1 is caused by germline heterozygous mutations in the NF1 gene, which encodes the oncosuppressor neurofibromin. The disease has a specific progressive course with multiple neurofibromas, in the initiation and growth of which NF1+/ – mast cells, macrophages and lymphocytes play an important role. Accordingly, the deficiency of neurofibromin impairs the differentiation and correct functioning of immune system cells. This is evidenced by the increased risk of leukemia in patients with NF1 and the role of NF1 mutations in the development of sporadic hematological malignancies. The development of neurofibromas is associated with the fact that NF1–/ – Schwann cells stimulate the migration of mast cells into the tumor microenvironment, which actively degranulate. The released cytokines promote neoangiogenesis, inflammation, fibroblast proliferation and the production of excess collagen. Therefore, in the treatment of NF1, the use of ketotifen and a kit/ fms kinase inhibitor is recommended. Macrophages and T-lymphocytes in neurofibromas do not provide an antitumor response, but promote inflammation and tumor growth. They produce STAT3 (signal transducer and activator of transcription 3), TGF-β, EGFR, IL-6, IL-4, and PD-1. Therefore, a promising direction is NF1 therapy with STAT3 inhibitors and immune checkpoint inhibitors that block programmed cell death ligand 1 (PD-L1). Activation of MEK signaling pathways in NF1 leads to PD-L1 stimulation; therefore, MEK inhibitors, which also suppress the RAS/RAF/MEK/ERK system, turned out to be effective in the treatment of NF1. For the treatment of sporadic malignant neoplasms, in the development of which NF1 mutations play a role, the developed methods of NF1 therapy can be used.

Relevance. The topicality of the work is determined by the wide spread of hypomagnesemia among the people, which makes it necessary to correct it. The aim of the work is to elucidate the cell-mediated response of the thymus mastocytic link to magnesium deficiency and its correction by the mechanoactivated form of magnesium orotate. Materials and Methods . Animals with drug-induced magnesium deficiency (administration of furosemide 30 mg/kg for 14 days) were administered either the initial preparation Magnerot (Magnerot, Vervag Pharma, Germany), or its mechanoactivated form. The level of magnesium in the blood was determined by test systems ARKREY (Japan). The concentration of magnesium in the thymus tissue was determined by the method of emission spectroscopy with inductively coupled (argon) plasma on an atomic emission spectrometer. Density of mastocytes and the indices of degranulation and granulolosis were calculated on paraffin sections of the thymus after coloration with toluidine blue. Results and Discussion . It was shown that furosemide administration the amount of magnesium decreased in the blood (from 1,750,08 to 0,9020,18 mmol/l, p0,05), but increased in the thymus (from 1,60,6 in the control to 3,71,2 mg/l); in the gland tissue, the number of mastocytes of morphotype A decreased and the number of mastocytes of morphotype D, after active degranulation, increased (by 7,1 times, p0,05). The type of mastocyte secretion in hypomagnesemia is represented by the merocrine variant. The administration of the initial magnesium orotate led to an increase in the concentration of magnesium in the blood to 1,150,25 mmol/l, which is 65,7% of the initial level, the amount of magnesium in the thymus remained elevated (3,41,1 mg/l), the number of actively degranulating cells (morphotype D) was increased. Mechanoactivated magnesium orotate restored the concentration of Mg2+ in the blood to 89,1% (1,560,18 mmol/l, p0,05) and decreased in the thymus (to 2,30,7 mg/l), restored the subpopulation of mastocytes saturated with heparin (type A), reduced the number of mastocytes of morphotype D. Conclusion . The mechanoactivated form of magnesium orotate has a normalizing effect on the population of thymic mastocytes, shows pronounced immunomodulatory activity, which allows us to consider it as a potential therapeutic agent for clinical testing in the complex therapy of hypomagnesemia and associated immunodeficiency.

The present review considers the role of mast cells (MC) and tryptase levels in various pathological conditions in children and adults. The main causes of hypertryptasemia are presented, as well as a list of the most important stimuli that can cause activation of MC. Cliical allergologists should focus their clinical practice on the patients with anaphylaxia and suspected MC activation syndromes. Moreover, hypertryptasemia (> 20 ng/ml) is considered an additional diagnostic criterion for systemic mastocytosis, according to the WHO recommendations. As a rule, the level of tryptase is constantly elevated in most patients with systemic mastocytosis, whereas it is undergo changes in acute IgE-mediated hypersensitivity reactions. In cases of anaphylaxia, tryptase concentration should be determined in the patients during the first hours following onset of acute allergic reaction, and 24-48 hours later. Recommendations are given for determining tryptase levels in blood serum of the patients (basal and peak values), and algorithms are provided for usage of these indexes in various diseases. The article also provides the assessed threshold values of tryptase when diagnosing anaphylaxia, MC activation syndromes, and a novel disorder – alpha-tryptasemia. In the diagnosis of hereditary alpha-tryptasemia, as well as MC activation syndromes (primary and secondary), clinical manifestations in the patient and time dynamics of tryptase levels should be taken into account. The accumulated experience allowed to consider, first of all, frequency of severe allergic reactions (most often as anaphylaxia) in the patients with suspected MC activation syndromes. The syndrome of MC activation is characterized by excessive release of their granule contents without signs of clonal proliferation, which in many cases may be due to gene allele duplication, especially, TPSAB1 α-tryptase gene. For patients with hereditary alpha-tryptasemia, the most characteristic manifestations are represented by vegetative-vascular dystonia (orthostatic tachycardia), joint hypermobility, etc. Hence, determination of tryptase level (especially in time course) should be given more attention in the practice of clinicians. Difficulties with interpretation of the results arise in cases when tryptase concentration remains within normal range (up to 11.4 ng/ml), and the patient has clinically evident mastocytosis, or MC activation syndromes. If the patient has a history of anaphylaxia, especially after bites of hymenoptera insects, the TC activation syndromes should be excluded.

The purpose of this work was to study the relationships between urinary cytokines, mast cells and nerve growth factor (NGF) in the patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Sixty-eight women with clinically diagnosed IC/BPS were under study. Their mean age was 54.2±12.4 years. Urinary concentrations of interleukins (IL-1β, IL-6, IL-8), tumor necrosis factor-α (TNFα), and NGF were determined by ELISA technique. Mast cells were identified in biopsies of mucous membranes from urinary bladder harvested during cystoscopy. Statistical evaluation was performed by Statistica program in Microsoft Excel. Pearson correlation quotients were calculated. Depending on the type of IC/BPS, the patients were divided into 2 groups: group I included 36 patients with classic type of disease; group II comprised 32 patients with non-ulcer type of IC/BPS. No significant differences were revealed between the groups. In 13.9% of patients from group I, the onset of clinical manifestations of the disease was observed at the age of less than 40 years; in group II, 28.1% of the examined mentioned appearance of the disease symptoms at this age. The levels of IL-1β in the patients from group I was 2.4 times higher than in controls (p < 0.05). IL-6, IL-8 and TNFα concentrations exceeded control values by 2.0 (p < 0.05), 2.5 (p < 0.05) and 2.0 times (p < 0.05), respectively. In the patients from group II, the content of IL-1β, IL-6, IL-8 and TNFα was 2.4 (p < 0.05), 2.0 (p < 0.05), 2.0 (p < 0.05) and 1.9 (p < 0.05) times higher than in the control group, respectively. There were no significant differences between groups I and II, in IL-1β, IL-6, and TNFα levels, except of IL-8 in women of group I that was 20.3% higher than in group II. The urinary NGF level in the patients with IC/BPS exceeded the control level 1.6 times (p < 0.05) for group I, and 1.5 times (p < 0.05) for group II. The number of mast cells in the patients of group I was significantly higher than in controls and in group II, i.e., 1.6 (p < 0.05) and 1.4 times (p < 0.05), respectively. In most cases, a direct weak correlation was revealed between the indices. Only in group I, a moderate correlation (r = + 0.508) could be detected between IL-1β and mast cells. Determination of cytokine levels allows to detect activation of inflammatory cells in bladder tissue and provides an opportunity for developing diagnostic strategies. Increased numbers of mast cells may indicate the importance of these cells in the disease progression, whereas elevated levels of NGF in urine suggests that IC/BPS may be caused by chronic inflammation.

Introduction. The causes and mechanisms of interstitial cystitis / painful bladder syndrome (IC / PBS) remain poorly understood. The pathogenesis and the etiology of the disease is still not clearly defined. Of great interest is the role of epidermal growth factor (EGF). Due to the complexity of the pathophysiology of IC / PBS, several animal models are used to better understand the mechanisms of this disease.Purpose of the study. to determine the level of epidermal growth factor (EGF) and its association with leukocytes and mast cells of the bladder tissue in animals with experimental models of interstitial cystitis / painful bladder syndrome.Materials and methods. IC / PBS modeling was carried out on 29 individuals of white New Zealand female rabbits, which were divided into 4 groups. EGFs were determined in blood and urine by ELISA. Cellular changes in tissues were assessed by histological method.Results. A high level of EGF in urine was detected in groups 1 and 2, exceeding the intact group by 33.3% (p

In obstetric and gynecological practice progesterone is often used in cases of miscarriage. The negative effect of progesterone on testicles of rats has been proven. However, the effects of progesterone introduction during pregnancy on fetal ovaries are not sufficiently studied require further study. Objective. To determine the peculiarities of the distribution and dynamics of ovarian connective tissue cells (fibroblasts, fibrocytes, macrophages, mast cells, lymphocytes) in the offspring of rats receiving progesterone during pregnancy. Object and methods. The ovaries of laboratory rats were investigated on the 9th, 14th, 21th, 30th, 45th, 60th and 90th day of postnatal life. The rats included in a study were divided into 3 groups: I intact, II experimental group of rats, who were injected by 0,33 ml of progesterone oil solution on the 15th to 18th day of pregnancy and III control group of rats which were injected by 0.9% Sodium Chloride solution in equivalent dosage. Serial sections were stained with àlcian blue with a 0,2Ì as a critical concentration of MgCl2 . Results and discussion. In animals of the experimental group, compared to control group, a significant increase in the number of fibrocytes and a significant decrease in the number of fibroblasts up to 90 days of life was observed. The macrophage and lymphocyte level changed wavily during the observation period with a tendency to decrease in experimental animals at the end of the third month of life. The number of mast cells in animals of the experimental group increased from the 30th to the 90th day of life inclusively compared to the control group data. Conclusions. The established changes may reflect a disturbance in the processes of growth and maturation of the follicles, as well as in ovulation processes after the antenatal affection of progesterone on the offspring ovaries.

This minireview summarizes some of our results on the structure, origin, and functions of thymic mast cells, as well as their role in stress-induced thymic atrophy. A comparison of the thymic mast cells with the connective tissue and mucosa mast cells is carried out. The morphological and cytochemical similarity of thymic and mucosa mast cells has been proven. The mechanisms of neuro-mast cell interaction, as well as the features of intercellular signaling are analyzed. Another aspect of the review is related to the assessment of thymic mast cell functions in stress-induced atrophy. It is hypothesized that the main function of these cells under stress is to regulate the T-cell emigration. The role of the thymus as an endocrine gland is also discussed. Probably, its endocrine function is mainly associated with the thymic mast cells which are regulated by the nervous system. Regardless of their localization and despite their hemopoietic origin, all mast cells are an important addition to the nervous system. They are a unique combination of both receptor and effector cells located in all organs and tissues. The mast cells supply the central nervous system with information about any local changes in tissue homeostasis and enhance local nervous influences. At the same time, mast cells are extremely important for neuro-immune communication as well as their mutual control on local defense reactions and mucosa conditions.

The goal of present study was to determine the levels of mast cell tryptase (MCT) in whole saliva, and blood serum IgE antibodies in patients with intolerance for dental prosthetic materials (IDM) before and after removal of prosthetic constructs. We have conducted examination of the patients suffering from the IDM symptoms, who were divided into 2 groups depending on the time span between the end of prosthetic treatment and emergence of pathological symptoms: group 1 (n = 19), 1 to 14 days (symptoms emerged immediately after treatment); group 2, (n = 18), IDM symptoms occuring 6 months to 5 years later; group 3 (n = 16), controls without complaints for IDM. Whole saliva (WS) samples were collected before removal of prosthetic constructs and 1 month later. In group 1, salivary MCT was detected in 16 subjects (84.2%) before removal of prosthetic constructs, while 1 month after MCT not detectable in saliva (p < 0.001). Salivary MCT in control group was not detected both before and after removal of prosthetic constructions. Hence, mast cell tryptase in whole saliva could be a diagnostic marker for intolerance to dental materials. In group 1 of the patients, we detected IgE antibodies to Ni-HSA in 78.9% of patients, IgE antibodies to Cr-HSA in 68.4% of patients and IgE to Co-HSA in 52.6% of patients. Salivary MCT levels strongly correlated with IgE levels to Ni-HSA (Rspearman = 0.9; p < 0.05), showing moderate correlation with Cr-HSA (Rspearman = 0.7; p < 0.05). The data obtained suggest some prevalence of immediate type immune reaction against dental materials. Notable local increase of MCT level could be an important diagnostic marker of local inflammatory process initiation. MCT in whole saliva was found only in 3 patients (16.7%) from group 2; those had IgE antibodies to metal ions in blood serum, thus indicating IgE-dependent reaction type. Other patients from group 2 were likely to develop a different type of allergic reaction, e. g. delayed or granulocyte-mediated response. To perform reliable diagnostics of allergy to the components of dental materials, it is reasonable to measure salivary MCT before and after removal of prosthetic constructs. Salivary MCT level monitoring allows to confirm a role of prosthetic constructs in IDM emergence, and a need for their replacement.

Introduction. Mechanisms of mass lymphocytes’ emigration from thymus are still unclear. The process of lymphocytes migration and mechanisms, which provide it, form one of the important problems of immunomorphology. Aim of the work: to establish the peculiarities of newborn thymus structure and to reveal pathways and mechanisms which provide lymphocytes’ emigration from thymus. Materials and methods. Morphological, histological and histochemical analyses of 160 rats’ thymuses from birth up to the 7th day after birth were conducted and discussed. The animals were handled according to the European Commission Directive (86/609/EEC). The profound microscopic analysis of cell contents, lymphatic vessels morphology in morpho-functional areas of rats’ thymuses during the first week after birth in 4 hours interval was carried out. All quantitative results were estimated by the statistic methods. Results. It is settled that thymus specific density tightly depends on the quantity of degranulated mast cells, absolute quantity of microcirculatory vessels, especially of lymphatic ones. The index of specific density, lymphocyte-epithelial index change wavy during the first week after birth every 12 hours. These changes are followed by the changes of extracellular matrix structure, absolute quantity of small lymphocytes in thymic cortex and lymphocytes’ adhesive properties. The key periods are: from 0 till 2, from 12 till 16, and from 108 till 120 hours after birth. At that time discrete migration of lymphocytes from the thymus occurs through paravasal lymphatic vessels. After temporal edema reduction, lymphatic vessels turn to be empty, their quantity decreases. Conclusion. Therefore, emigration of lymphocytes from thymus takes place through lymphatic vessels on the top of periodical short-term local edema.

Mast cell is a traditional cell for wound healing, but their content in the wound after transplantation of autoand heterofibroblasts and dermal equivalent on the basis of these cells remains poorly studied.Aim. To study the morphological structure, collagen formation, angiogenesis and content of mast cells in biopsy materials of the newly formed epidermis and dermis on the 12th day of their recovery in a model ischemic wound after administration of auto- and heterofibroblasts and after transplantation of dermal equivalent with heterofibroblasts.Materials and methods. The study was performed on 28 white mature mice of the C57 / B1 line aged up to 1 year. 0.4 ml of suspension with 1.33 million fibroblasts in growth medium DMEM F12 (Lonza) and in dermal equivalent were administered around and into the bottom of skin surgical model wound in the scapular region. The scar was embedded in paraffin and stained with hematoxylin and eosin, according to Weigert-Van Gieson, and kit for mast cells staining (Biovitrum).Results. On the 12th day epidermis is thicker after introduction of autofibroblasts, but it is more differentiated after transplantation of dermal equivalent with heterofibroblasts. Angiogenesis is also most active after the administration of autofibroblasts. Fibroblasts production of collagen fibers in granulation tissue, angiogenesis and the content of functionally active mast cells indicates the most favorable influence of autofibroblasts transplantation on the wound healing.Conclusion. The effect of dermal equivalent with heterofibroblasts differs from exposure autofibroblasts by several percent: the area of collagen fibers – by 2%, the area of blood vessels − by 5%, the index of degranulation of mast cells – by 4%.

Mastocytosis is relevant to heterogeneous disease group characterized with redundant accumulation and proliferation of mast cells in tissues. The skin form of mastocytosis is mainly occurs in children. The article contains the current data on etiology, pathogenesis, classification, clinical forms, diagnosis, prophylactics and mastocytosis treatment at children.

Objective: To examine the applicability of IHC staining method: with TGF-β1 antibodies (serial examination, statistically processed results) and with mast cell tryptase antibodies for injuries vitality determination., Material and Methods: 261 skin autopsy samples with mechanical injuries from 29 persons were divided to 3 groups (87 in each group): vital injuries, postmortal injuries, control non-injured samples. A routine histological examination using standard H&E stain and IHC both with TGF-β1 and mast cells tryptase antibodies was performed., Results and Conclusion: The positive TGF-β1 staining (score 2-3) was found in keratinocytes in vitally injured skin and the negative or weak one (score 0-1) was found in control postmortally injured and non-injured samples. Additionally, dermal TGF-β1 expression was found in some vitally injured skin samples. The difference between vitally injured skin and control samples was statistically significant ( p <0.05). No significant difference of dermal mast cells density in groups 1, 2, 3 was found.

Study of gum disease and salivary glands often involves the study of mast cells, which are known to belong to a group of cellular factors innate immunity. The purpose of this investigation was to determine characteristics of the cytoplasmic biopolymers of the mast cells in gums and large salivary glands in human being during 23 solar cycle with the help of histochemical staining. The material was taken from men, who got dead during road accident. With the help of the investigation results can make the conclusion, that characteristics of the gingival and large salivary glands mast cells have seasonal character. And characteristics of the mast cells of the gingiva and parotid glands , besides seasonal character, have chronobiological component that is under the influence of the solar cycle maximum phase.

Mast cells are an integral component of the pathogenetic chain of immune inflammation in the body's tissues in different diseases. The mechanisms underlying the proinflammatory effects of mast cells remain inadequately investigated. Their study may contribute to the optimization of therapy for different diseases, including chronic arthritis.

Introduction. The problem of the quality of life of patients with the chronic kidney disease stage VD treated by hemodialysis is becoming more and more urgent in medicine. One of the most common factors that worsen in patients with chronic kidney disease (CKD) that are treated by hemodialysis – skin itching occurs in 50.0-60.0% of these patients. Itching affects sleep, working capacity, causes depression, sometimes suicidal thoughts. Aim. To increase the efficiency of treatment of patients with CKD and skin itching, which are treated by hemodialysis, with the use of ultraviolet irradiation on the basis of the study of the effect of skin itching on the quality of their life, the state of decomposing cells and proinflammatory cytokines. Materials and methods. The study involved 109 patients with CKD of the VD stage who were undergoing hemodialysis at the Lviv Regional Clinical Hospital and Kyiv City Scientific and Practical Center of Nephrology and Dialysis. The control group was made up of 20 healthy individuals who, according to age and gender, corresponded to the patients of the examined group. There were studied the parameters of the pruritus, the quality of life, the levels of proinflammatory cytokines (IL-1β, IL-17, MCP-1), the presence and activity of the skin mast cells, depending on the presence / absence of the itching skin. Was carried out the ultraviolet radiation treatment and was examined its effect on the itching, the levels of cytokines and the quality of life in 109 hemodialysis patients. Results. In 56.0 % of patients with the chronic kidney disease stage VD was revealed the skin itching which is inversely correlated with the most indicators of the life quality. Proinflammatory cytokines potentially reflect the activity of pruritus in 58.3 % of patients. Was noted a higher number and activity of mast cells in patients with the pruritus compared to patients without it. As a result of the comparisons between proinflammatory cytokines and mast cells was found a direct connection of both in patients with the pruritus. In 100.0 % of patients the ultraviolet radiation treatment helped to eliminate the skin itching. The positive influence of the ultraviolet radiation retained in 45.8 % of patients within one year. The levels of the proinflammatory cytokines in patients with the pruritus decreased in two weeks after the ultraviolet radiation course. Conclusions. It was found that in patients with the CKD stage VD treated by the hemodialysis the itching of the skin significantly impairs the quality of life. It was also found that the ultraviolet radiation treatment reduced the itching of the skin in these patients, resulting in the improvement of the quality of life by 14.8 %.

We investigated the influence of factors of the acute phase of inflammation (purified anaphylatoxins C3a and C5a, pentraxin C-reactive protein (CRP), and aggregated. IgG (aIgG) — as an analogue of circulating immune complexes) on the adhesive interaction of human mast cells (MC) with human fibroblasts (FB). HMC-1 MC line and primary human foreskin FB were used. MC or FB were treated with each of the studied inflammatory proteins within 24 h and then the changes in their adhesive properties were examined. Cell adhesion was assessed by flow cytometry. The results showed that all studied proteins increased MC adhesiveness, whereas FB adhesiveness was increased only by anaphylatoxins. Stimulation of the adhesive properties of the MC was associated with increased expression of CD11b and ICAM-1 molecules.

Mast cells (MCs) are highly differentiated and multifunctional immune cells. The importance of TC has been established not only as mediators of allergic reactions, but also for the development of an immune response, the occurrence of certain autoimmune diseases, tissue homeostasis, the formation of immunotolerance and metastasis of malignant tumors. MCs are present in the endometrium of women in various value depending on age, the phase of the menstrual cycle, the presence of pregnancy. Out of pregnancy, MCs are involved in the cyclic transformation of the uterine mucosa. At the onset of pregnancy, MCs stimulate the process of remodeling of the spiral arteries, the production of leukemia-inhibiting factor (LIF), which is the main implantation factor, and contribute to the formation of an immunotolerant state of the mother in relation to the fetus. Obstetric complications are accompanied by a variable content of MCs, which is associated with different genesis of diseases. A low amount of MCs is associated with impaired implantation and the development of early preeclampsia, an increased content of MCs is observed in the presence of a pathological inflammatory reaction that accompanies late preeclampsia. This review is devoted to the significance of MCs and their mediators in the physiological course of pregnancy, as well as their participation in the pathogenetic mechanisms of pregnancy complications.

Helicobacter pylori induced gastritis accounts for 70% of cases in the structure of this pathology. Features of the long-term inflammatory reaction of the mucous membrane are directly related to the mechanisms of bacterial pathogenicity, and features of immunogenesis within narrow limits of the specific tissue microenvironment of organ structures. Mast cells appear to be one of the key players (promoters) in the regulation of the inflammatory mediator cascade and the formation of cytokine-induced expression. Possessing a wide arsenal of biologically active substances, mast cells are able to participate in the formation of the immune response and resistance of the gastric mucosa, modulating both pro- and anti-inflammatory effects. The antigen-presenting features of mast cells are of interest in terms of interaction with H. pylori and induction of mucosa bacterial colonization. The aim of study was to assess the mast cell tryptase profile of the gastric mucosa in the immunopathogenesis of H. pylori-associated inflammation. Material and methods . The study included 19 biopsies of the gastric mucosa with unknown status of H. pylori infection. Microslides were stained with hematoxylin and eosin, and Giemsa's dye for plain microscopy. H. pylori infection of the gastric mucosa was detected using the immunohistochemical method. Using double immunofluorescent labeling, localization of tryptase-positive mast cells and H. pylori strains was detected. Results . In patients infected with H. pylori (n=12), there was a significant increase in the number of tryptase-positive mast cells (177.99±30.55 vs 88.58±11.49; p<0.05) with activation of secretory pathways and release of protease into the extracellular matrix of the gastric mucosa. The quantitative parameters of mast cells in the group of patients with an undetected pathogen and signs of a chronic inflammation of the gastric mucosa were statistically significantly lower than in the group of infected patients. Co-localization of tryptase-positive mast cells and H. pylori strains (with the formation of areas of large free-lying granule accumulation around the glands with pronounced degree of H. pylori contamination) was detected in gastrobiopsy specimens, the fact evidencing their close involvement in the development of inflammatory reactions of the gastric mucosa. Conclusion . The study demonstrated the features of mast cells and H. pylori interaction revealing previously unknown aspects of gastritis pathophysiology. The data obtained contribute a valuable insight to choose a treatment strategy for H. pylori-associated gastritis., Competing Interests: The authors declare no overt and potential conflict of interest related to the publication of this article., (Copyright© GEOTAR-Media Publishing Group.)

Aim: to evaluate the level of nerve growth factor (NGF) in the blood and urine and mast cell infiltration of the bladder wall in a model of interstitial cystitis/bladder pain syndrome (IC/BPS) and to analyze their relationships., Materials and Methods: IC/BPS modeling was performed on 38 female rabbits, which were divided into 4 groups. In the group 1, IC/BPS was simulated by an instillation of 70% alcohol into the bladder, while in group 2 and 3 animals own urine and normal saline were injected into the bladder wall. The group 4 consisted of intact animals. The NGF level was determined by ELISA. To determine the concentration of mast cell in tissues, each cross-section was divided into 10 sections. The severity of mast cell infiltration was evaluated in each area using the following scale: 0 - no mast cells; 1 - less than 20 cells; 2 - 20-45 cells; 3 - more than 45 cells. The points of all 10 areas were added up, divided by 30 (the maximum possible score) and multiplied by 100., Results: An increase in the NGF level in the blood and urine was seen in different models of IC/BPS, but it was significantly more pronounced in the group 2 (toxic model). Mast cells were determined only in the group 1 (0.25+/-0.707) and 2 (14,200+/-5,796). In animals with the urinary toxicity model, mast cell activity was significantly higher in comparison with those in the model with an instillation of 70% alcohol (p<0.001). The level of NGF in blood and urine correlated in different directions. Mast cell proliferation and activation was determined in case of impairment of the bladder wall integrity by the injection of urine., Conclusion: Our animal model of IC/BPS, which was created by instillation of 70% alcohol into the bladder and the injection of urine into the bladder wall, showed an increase in the level of NGF in urine and blood and the concentration of mast cells. These findings, as well as relationship between these values indicate the development of neuroimmune inflammation in this pathological condition. Considering the involvement of many factors in the pathogenesis of this syndrome, further researches are required.

Objective: To study the expression of IL-17A in the inflammatory infiltrating cells in the plaques as one of the key points in the pathological process in moderate to severe psoriasis., Material and Methods: The material obtained from 50 patients with moderate and severe psoriasis was examined by an indirect immunofluorescence assay to determine the composition of cell infiltrate and the type of IL-17A-producing cells in the foci of lesion. The markers of lymphocytes (CD3), dendritic cells (CD11c), neutrophilic granulocytes (Mpo), and mast cells (Trp) were used. The proliferative activity of basal keratinocytes (Ki-67), the expression of IL-17A, and the co-expression of IL-17A, Mpo, and Trp were also studied., Results: A positive correlation was established between the count of neutrophilic granulocytes in the infiltrate, the expression of IL-17A, and the number of neutrophils expressing IL-17A with the duration of the disease and the severity of the patient's condition., Conclusion: Neutrophilic granulocytes and their expression of IL-17A play one of the key roles in the pathogenesis of psoriasis.

Objective: To study the morphological features of the microenvironment of a tumor nodule in the eyes with uveal melanoma, focusing on mast cells., Material and Methods: A total of 43 enucleated eyes with uveal melanoma (260 histological specimens) were examined. The patients' age averaged 54±2.7 years. The morphopathological types of tumors were as follows: epithelioid-cell (n=9; 20.9%), spindle-cell type AB (n=15; 34.9%), and mixed-cell (n=19; 44.2%). The tumor prominence was 4.7±1.3 mm; the base diameter was 13.5±3.3 mm. Statistical methods, such as Microsoft Excel, Statistica 10.1, Spearman's rank correlation coefficient (rs), were applied., Results: Mast cells in the microenvironment of uveal melanoma were present in 18 (41.9%) of the 43 eyes. There was a significantly higher correlation between the mixed-cell type of tumor and the accumulation of mast cells (r s =0.636). The correlation coefficient (rs) of the number of mast cells with the degree of tumor pigmentation in terms of densely and weakly pigmented forms was 0.571 and 0.717, respectively. Tumor invasion through the sclera was detected in 7 (16.3%) eyes with mast cells (r s =0.395). Tumor growth in the emissarium in the presence of mast cells was determined in 8 (18.6%) cases (r s =0.469). Comparison established a correlation between the number of mast cells and the sections of tumor blood vessels (r s =0.21). Granulated cells were noted in 15 (34.9%) cases; degranulated ones were seen in 3 (7%) cases of the 43 examined eyes. with an ejection of granules around the tumor cells, which may be evidence of their interaction. Granules were ascertained to be released around the tumor cells, which may be suggestive of their interaction., Conclusion: The study of the mast cell population as one of the components of the tumor microenvironment can be used to elaborate novel approaches for the targeted treatment of uveal melanoma, in particular for its impact on tumor angiogenesis, by using mast cell inhibitors. Therefore, it is relevant and promising to conduct further investigation of mast cells in uveal melanoma.

The purpose of this study was to assess the possibilities of identifying mast cells using different histochemical and immunohistochemical methods and elucidating the features of their localization in the human pineal gland. The undertaken study showed that mast cells are an essential component of the human pineal gland, regardless of age. The data obtained indicate an increase in the number of mast cells in the pineal gland with age. Mast cells are mostly located in the pineal stroma and their preferred location has not been related to concrements, cysts or melanin accumulations. Mast cells in the pineal gland are predominantly non-degranulating, which indicates their inactive state. The detectability of mast cells in the pineal gland depended significantly on the applied method of staining of the preparations. The largest number of mast cells was revealed by tryptase immunohistochemistry, which should be used to accurately determine the population of mast cells of the pineal gland.

The influence of bone marrow autotransplantation on neurotransmitter structures of appendix vermiformis was studied. The study revealed that an increase in the number of neurotransmitter structures (mast and granular luminescent cells), having a high content of catecholamines and serotonin was noted in old rats in 40 min after bone marrow autotransplantation. In the center of vermiformis appendix lymphoid nodes reproduction cellular programmed differentiations having a high content of neuroamines are determined. In 2 hours after bone marrow autotransplantation their number decreases, the content of catecholamines and serotonin reduces as well. In the immunohistochemical reaction increase in proliferative activity of cells both in proper t. mucosa plate crypts and appendix vermiformis lymphoid nodules is observed up to 40 min of experiment. In 2 hours Ki-67 positive cells reduce both in t. mucosa and t. s/mucosa of appendix vermiformis.

Mast cells (MC) are present in the skin and mucous membranes, lymphoid organs, intestine wall and brain, where they are located close to the blood and lymphatic vessels and nerve terminals. As a source of a large number of biologically active substances, many of which are released quickly into the environment as a result of degranulation process, mast cells play an essential role in the regulation of physiological processes in the tissues where they are present. Changing the MC population and activity in the tissues during aging is associated with age-related changes of the skin and mucous membranes, the development of central nervous system disorders such as itching, headache, joint and muscle pain, memory loss, attention deficits, depression, anxiety and depressive disorders, autism, Alzheimer's disease and multiple sclerosis.

The aim of this study was morphological analysis of corneal disks and conjunctival biopsy specimens in order to disclose the mechanisms of development of epithelial-endothelial dystrophy (EED) and validating pathogenetically-based therapy. Twenty-five patients were observed, 11 of these with implanted intraocular lenses of different localization. EED developed for 1 to 5 years. Sixteen biopsy specimens of the conjunctiva and 21 corneal disks were examined. The composition and index of inflammatory infiltrate, status and compactness of conjunctival vessels, severity of fibrosis, and mast cell degranulation were assessed. Mast cells play a positive role at the initial stages of tissue and cellular response to injury by regulating the formation of extracellular matrix and fibroblast proliferation. At the reparative stages of immune inflammation of the conjunctiva, mast cells are virtually the only cell population; fibrosis and sclerosis develop when the capillary bed is reduced, causing ischemic involvement of the anterior segment of the eye and dystrophic processes in the cornea. A differentiated approach to treatment of EED at the stages of immune inflammation and fibrosis is emphasized.

The biorhythmologic changes of tissue basophils (mast cells) have been investigated of mater rats in frontal, temporal and occipital regions of dura mater during the noise-vibration stress. Local differences were found in biorythmological characteristics of tissue basophils before and after vibration. The investigated regions of dura mater after noise-vibration stress the magnitude of harmonics, mesor and the amplitude of fluctuations increased greatly. But, judging by their values, in the temporal region the rhythm stability was lower than that in the frontal and occipital. The tissue basophils of various regions of dura mater react in a different way to the noise-vibration stress.

Lungs of 20 rats flown aboard Cosmos-936 for 18.5 days and sacrificed within 5-13 hours (8 weightless and 4 centrifuged rats) and 25 days (4 weightless and 4 centrifuged rats) after recovery were studied histologically. An identical number of lung specimens were withdrawn from rats of synchronous and vivarium controls. Lungs of the flight rats did not show any pathological changes or morphological signs of prolonged congestion, thus indicating the lack of hypertension in pulmonary circulation. Lungs of the flight rats exhibited an increased leukocyte count, which was more marked in the weightless rats killed 8-13 hours postflight. The elevation in the count of neutrophilic leukocytes in the flight rats was due to peripheral neutrophilia which is a manifestation of an acute stress-reaction. An exposure of rats to artificial gravity was responsible for a lesser increase in the count of neutrophilic leukocytes.

Origination of the breast neoplasms was studied in female rats totally gamma-irradiated (a single dose of 200 r) at the age of four weeks. The first neoplasms were found in rats sacrificed 6 months after the exposure; control unexposed rats developed the breast neoplasms only by the 15th month since the beginning of the experiment. By histological criteria all these neoplasms were benign in both groups of animals. Most cell and eosinophilic leukocyte count in the mammary gland tissue showed quantitative changes in the eosinophilic leukocyte count, and a change of the mast cell reaction during the radiation blastomogenesis.

The cell content of mammary stroma infiltrate (lymphocytes, plasmocytes, eosinophilic leukocytes, macrophages, mast cells) was determined in the process of physiological involution, in dyshormonal hyperplasia and mammary gland tumours of old rats. Studies on the physiological involution revealed the existence of correlations between some pairs of the test types of free cells. Under dyshormonal transformation and tumour growth the former correlations disappeared and the new ones were formed, not occurring during the physiological involution of the mammary gland epithelium.