Home – Home – Jornals – Siberian Scientific Medical Journal 2019 number 5

The growth rate of the world medical tourism sector is currently considered among the highest in comparison with other tourist segments. There are a large number of scientific conferences on the topic of medical tourism in the world. It spawned a new concept of modern healthcare. In the context of global economic competition, the phenomenon of medical tourism makes medicine develop more rapidly. In this regard, the authors conducted a search and review of relevant sources on the issue of medical tourism. In order to select and summarize sources, a search was made for the current literature. The review presents the nature, problems and possibilities of medical tourism in the framework of the literature studied. Unfortunately, the issue of the development of medical tourism is relatively little studied, this is confirmed by the small number of original studies. At the same time, medical tourism as a phenomenon of global health is growing, and therefore requires proper monitoring, government regulation and the development of the necessary infrastructure.

Recently, lithium salts have been considered as potential compounds for targeted therapy that can reduce tumor growth. There are a large number of publications indicating the effects of lithium on the signaling pathways used by tumor cells for growth and development, and have demonstrated that lithium can be used as antitumor agent in experimental oncology. The promise of using lithium salts to develop anticancer drugs is related to the fact that lithium has 2 main intracellular targets: glycogen synthase kinase-3β (GSK-3β) and inositol monophosphatase (IMPase), the inhibition of which by lithium can induce cancer cell death by apoptosis or autophagy. Lithium has been shown to block the proliferation of cancer cells by cell cycle arrest in the G₂ /M phase, and also stimulates apoptosis and autophagy in cancer cells. This review summarizes data on the transport of lithium across cell membranes, characterizes its main intracellular targets and presents the results of studies in which lithium was used in experimental cancer therapy of various localization with an emphasis on signaling pathways used by cancer cells for growth and metastasis.

This review summarizes the literature data on the role of lithium compounds in modern pharmacotherapy of various diseases of the central nervous system. Attention is also paid to other therapeutic properties of lithium in atherosclerosis, cardiovascular diseases, diabetes, hematopoietic disorders, inflammation, and diseases of the urinary system. Possible ways of delivering lithium into the body have been charted, in particular, when lithium salt is combined with a sorbent (solid porous carrier). Such compounds have additional therapeutic properties. Data on the significance of lithium compounds in studies on models of diseases of the nervous system in animals are analyzed. Among these models, models of neonatal ischemia/hypoxia of the brain in vivo , neurodegenerative diseases, psychopathological states (aggressiveness, depression) and craniocerebral injury are discussed. There are researches in which the results of the lithium preparations use in clinical practice are investigated. It emphasizes the influence of genetic factors on the lithium effects. Particular attention is paid to the possibility of preventing the toxicity of lithium compounds for the body. The currently known molecular mechanisms of lithium action are discussed: inhibition of glycogen synthase kinase 3β (GSK-3β) and inositol monophosphatase 1 (IMPA1), which have key value for autophagy, oxidative stress, inflammation, mitochondrial function, induction of neurotrophic factors, apoptosis. It was concluded that the study of the molecular pathways of the functioning of lithium compounds empowers understanding both the reasons for its effectiveness in the nervous system diseases and the mechanisms of action on other body systems.

Heart rhythm disorders are considered as changes in the normal frequency, regularity, and source of depolarization of the heart, as well as impulse conduction disorders. Cardiac arrhythmias can be caused by numerous reasons, as well as their combination. The review presents current data on the frequency, risk stratification and prognostic value of cardiac arrhythmias in patients with various internal diseases. The data on the increased risk of atrial fibrillation in gastroesophageal reflux disease, gastric diseases and inflammatory bowel diseases are presented. The spectrum of the most common arrhythmias in patients with chronic obstructive pulmonary disease and asthma, as well as thyroid diseases, diabetes mellitus and acromegaly is considered. The options for cardiac arrhythmias associated with the use of chemotherapeutic drugs in the treatment of hemoblastosis are considered separately. Modern ideas about the mechanisms of development of arrhythmias in various internal diseases are discussed. In most cases, cardiac arrhythmias are associated with both the direct effect of the underlying disease on the cardiovascular system and the systemic reactions that occur. However, to date, the question remains to what extent the myocardial state that precedes the underlying disease plays a role in the occurrence of cardiac arrhythmias. The significance of various congenital and genetic factors has not been clarified. These questions are essential for everyday clinical practice and require detailed scientific study.

This paper reviews current literature data on the participation of hydrogen sulfide (H₂S) in the pathogenesis of neurodegenerative disorders - Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS). In the CNS the level of H₂S is determined by the enzymes of its synthesis - cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). H₂S is a gasotransmitter, the action of which is realized through chemical and conformational modification of protein molecules simultaneously in spacious pools of cells - in a «broad field». The effects of H₂S are highly divergent when a certain threshold is reached, it moves from the neuroprotection to the neurodegeneration. The neurodegeneration is mediated by both increased (in ALS) and decreased (PD, AD, HD) levels of H₂S production, which is determined by the activity of different enzymes of its synthesis - CBS (PD, AD, ALS) or CSE (HD) - depending on the specificity of the certain disorder, that leads to the deployment of the especial pattern of neurological events. The disturbances in sulfur-containing amino acids metabolism and thiol-disulfide homeostasis are an integrative part in H₂S-dependent mechanism of the neurodegeneration. The opposite/divergent negative effect of H₂S, the involvement of different enzymes of its synthesis and some products of transformation in the pathological process suggest about the dual nature of H₂S as a signaling molecule at neurodegenerative disorders.

There is limited evidence in favor of a carcinogenic effect of radiofrequency electromagnetic fields, based predominantly on epidemiologic research. However, epidemiologic studies of radiation effects may be associated with bias. The brain tumor incidence has in fact not reacted to the tremendous increase in the mobile phone use. A moderate incidence increase in some countries and age groups can be explained by improvements of the imaging technology. The risks reported by epidemiological studies are from electromagnetic radiation of non-thermal intensity. However, UHF-therapy of thermal intensity has been widely used for the treatment of otorhinolaryngolical and other diseases since the 1960s. Associations of the UHF-therapy with enhanced cancer risk have never been reported. Radiofrequency electromagnetic fields of solar and atmospheric origin are components of the natural environment; they are subject to considerable fluctuations. Accordingly, there must be living organisms’ adaptation. The problem can be solved by large-scale animal experiments with registration of the life duration. In some experiments, exposed animals had higher average life duration than controls, which may reflect a biphasic dose-response of hormetic type. Examinations of animals and necropsies incur expenditures that could be used to enhance the number of animals and statistical significance. To make results of experiments transferable to professional exposures or the use of mobile phones, dose rates must be comparable to those in humans.

Aim of the study was to investigate the possible mutagenic properties of a new drug based on a lithium-containing substance - a complex of lithium citrate, polymethylsiloxane and aluminum oxide. Material and methods. Methods for testing mutagenicity using chromosomal aberrations in the bone marrow cells of CBA mice and somatic recombination in Drosophila melanogaster were used. Results. It was shown that a single intragastric administration of drug at a dose of 5000 mg/kg and a fivefold course of administration at a dose of 400 mg/kg to CBA mice did not increase the level of cytogenetic disorders in bone marrow cells. The study of the lithium complex drug in a somatic mosaicism test revealed that the preparation at a dose of 2000 mg/kg does not increase the frequency of mutations in Drosophila melanogaster . Conclusion. A single intragastric administration of the studied drug at a dose of 5000 mg/kg and its course administration (400 mg/kg × 5) do not increase the level of cytogenetic disorders in the bone marrow cells of CBA mice. In the somatic recombination (mosaicism) test system on D. melanogaster , no increase in the appearance of mutant setae and spots on the body and head was observed when using yellow and singed markers. The results of the study indicate that the studied drug does not have mutagenic properties.

The purpose of systemic treatment in patients with breast cancer is based largely on the molecular characteristics of the primary tumor, but many clinical recommendations suggest also the study of metastatic nodes with an assessment of their receptor status (estrogen receptor ER, progesterone receptor RP, human epidermal growth factor receptor 2 Her2/neu). This is due to the fact that according to numerous studies, the discrepancy between the status of the primary tumor and the secondary nodes can reach high rates: 3-54 % for ER, 5-78 % for RP, and 0-34 % for Her2/neu. At the same time, more and more data actively demonstrate the imperfection of immunohistochemical analysis and the need to study additional parameters to improve the quality of diagnosis of patients with breast cancer. Material and methods. A morphological and immunohistochemical study of the tumor tissue of the primary node and axillary lymph nodes was performed in 199 patients with breast cancer (T1-3N0-3M0) using standard methods, and RT-PCR was also studied with the expression of 24 genes. Results. The incidence of differences between the molecular phenotypes of the main tumor and metastatic axillary lymph nodes was 26 (26 %) of 99 cases. Most often, differences were noted in cases of breast cancer with luminal A type - 13 cases (50 %). According to the results of a comparative PCR analysis of tissue samples from the primary tumor and metastatic regional lymph nodes, only the expression of the CD68, ERSR1, GRB7 and MMD11 receptors was statistically significant. Conclusion. The results indicate the need for an integrated approach and additional methods for the diagnosis of breast cancer, which will undoubtedly improve the quality of planning and the effectiveness of systemic treatment in patients with breast cancer.

Was conducted histological study axillary and mesenteric lymph nodes in breast cancer induced by intramammary administration of N-methyl-N-nitrosourea, chemotherapy according to the CMF scheme (cyclophosphamide, methotrexate, 5-fluorouracil), operative removal of breast tumors (6.5 months from the beginning of the experiment). The results of the study. At chemotherapy of breast cancer, compared with the group with breast cancer without treatment, there was a decrease in the number of tumor cells in the axillary lymph nodes in comparison with mesenteric lymph nodes. The decrease in the area of the paracortical zone and the area of secondary lymphoid nodes remain in the axillary lymph nodes, in comparison with breast cancer without treatment. The reduction of the paracortical zone square remains in mesenteric lymph nodes. The area of lymphoid nodules with germinative centers decreases. The number of postcapillary venules with high endothelium and the number of macrophages in structural zones grow down. In the axillary lymph nodes after surgical treatment of breast cancer and chemotherapy in comparison with the treatment of breast cancer only with cytostatics, there is decrease in the area of the paracortical zone (with an increase in the number of small lymphocytes) and medullare cords. The area of lymphoid nodules with germinative and without germinative centers increases. In mesenteric lymph nodes, drainage function is reduced, increased the area of the paracortical zone, reduced the areas of lymphoid nodules with germinative centers and medullare cords (increased proliferative activity of cells), macrophage reaction in the cortical substance was revealed. Conclusion. The severity of structural transformations in cytoarchitectonics of the axillary and mesenteric lymph nodes depends on the treatment method.

The aim of the study was to fulfill correlation analysis of morphometry of the mesenteric lymph nodes and the concentration of cytokines in the lymph of the thoracic duct in breast cancer induced by intramammary administration of N-methyl-N-nitrosourea, chemotherapy according to the CMF scheme (cyclophosphamide, methotrexate, 5-fluorouracil). The results of the study. At breast cancer revealed positive correlation: in the germinative centers and medullary cords of cytokine IL-5 with mitotically dividing cells, chemokines MIP-1α with average lymphocytes, in the germinative centers of immunoblasts with cytokine GRO/KC, in the paracortical zone chemokine MCP-1 with macrophages, reticular cells with IL-6 and M-CSF, in the medullary sinuses chemokine GRO/KC with small lymphocytes and mature plasma cells (number which decreases). All this may indicate the activity of the local immune response in the lymph nodes aimed on the antitumor protection. After chemotherapy of breast cancer, compared with breast cancer without treatment, revealed positive relationship, which may indicate increased immunomodulatory and antitumor actions of cytokines: correlation of interferon IFNγ with small lymphocytes (number which increased) and macrophages in the germinative centers and mitotically dividing cells in the medullary cords, correlation in the germinative centers of immunoblasts with MIP-1α and increased of number small lymphocytes in T-dependent zone lymph nodes, correlation in medullary cords of interleukin IL-17 with mature plasma cells (number which increased) , correlation of interleukin IL-18 with mature plasma cells in medullary sinuses. Conclusion. Study of the correlation of the concentration of cytokines in the lymph of the thoracic duct with structural changes in the mesenteric lymph nodes revealed dependencies aimed at increasing the immunomodulating and antitumor effects of cytokines

This work represents the results of the study of the surrounding tissues reaction to the implantation of bioresorbable implants formed by the solution blow spinning from polylactic acid and ultrafine calcium phosphate powders, depending on the time and place of implantation. Using scanning electron microscopy it is shown that implants formed from randomly interwoven fibers have interconnected open porosity. It was established that the addition of calcium phosphate ultrafine powders does not cause changes in the formed implants structure. Histological investigation of tissue specimens from the implantation site revealed a high ability of created implants to successful integration with surrounding tissue after 15 days from the moment of implantation. Complete or partial implant resorption with substitution by own tissues was registered at 90 days after implantation. It was established that implantation of composite bioresorbable implants on the ilium bone stimulates the osteogenic process better than the implantation on skull bone within the same period. It was defined that scarification of the outer cortical plate in implant contact points with bone tissue increases the implants ability to stimulate osteogenic process. It was shown that the composite implants filled with calcium phosphate dibasic dehydrate in ultrafine powder form have the largest ability to stimulate osteogenesis.

Aim of the study was to investigate in a comparative manner associations between the parameters of central aortic pressure, office and ambulatory blood pressure with indicators of target organ damage. Material and methods. 47 consecutive outpatients and hospital patients (22 men and 25 women) aged 19-70 years were included in the open one-stage follow-up of a series of cases. The study program included anthropometry, measurement of office and ambulatory blood pressure, applanation tonometry of the radial artery, recording of resting ECG, echocardiography, biochemical blood analysis. In analyzing the data, the methods of descriptive statistics and the general linear model (GLM) were used. Results. Central aortic pressure is comparable to office blood pressure and, more than ambulatory blood pressure, was associated with indicators of left ventricular hypertrophy. Systolic central aortic pressure was associated with all electrocardiographic and echocardiographic indices used in the study. Of the central aortic pressure parameters characterizing the amplification and augmentation of the pulse wave, only non-augmented amplification of systolic pressure was associated with signs of left ventricular hypertrophy, but the amplification and augmentation of the pulse wave showed a sufficiently high degree of association with estimated glomerular filtration rate. Conclusion. The results of this study substantiate the relevance of using aortic pressure parameters in addition to traditional methods for determining blood pressure.

Purpose: to study the clinical and laboratory efficacy of the platelet autoplasma use in the complex treatment of endogenous uveitis associated with systemic diseases accompanied by macular edema. Material and methods. The study included 46 people (72 eyes) with endogenous uveitis and macular edema. The diagnosis was made on the basis of the ophthalmological examination, including visometry, tonometry, biomicroscopy, ophthalmoscopy, perimetry, B-scan, optical coherence tomography of the macular zone, photoregistration of the anterior, posterior segment of the eye. The examination was carried out on the 1st and 10th day of treatment. The main group consisted of 22 people (36 eyes) who underwent anti-inflammatory therapy and the introduction of platelet plasma in the region of the pterygopalatine fossa. The control group consisted of 24 people (36 eyes) receiving only anti-inflammatory therapy (diprospan 0.5 para-equatorially №1, dexazone 4 mg intravenously №5, intravenous lasix 2.0 ml №5, electrophoresis with prednisolone № 7). All patients underwent the definition of IL-4, IL-6, IL-8, IL-17 in tear fluid before the study and on the 10th day. Results. The significant increase in the concentrations of pro-inflammatory cytokines (IL-17A and IL-8) and IL-4 and IL-6 involved in the development of autoimmune response and chronic inflammation was found in the patients with endogenous uveitis and macular edema. The use in the treatment of endogenous uveitis with macular edema of platelet autoplasma leads to more pronounced improvement of clinico-ophthalmological parameters (improvement in visual acuity, retinal photosensitivity, and retinal thickness reduction) relating to the comparison group. A decrease in the activity of the inflammatory process was noted in the main group after treatment, which is manifested by a significant decrease in the concentrations of IL-17A, IL-8, IL-4, IL-6, relating to the data obtained in the comparison group. The proposed scheme of complex treatment allows reducing the frequency of relapses of the pathological process.

The purpose of the study is to evaluate the effectiveness of the shielding of leaded rubber plates in superficial radiotherapy of lower lip cancer of stage I-II. Material and methods. A comparison was made of the timing and severity of oral mucosa and alveolar ridge damage in patients who used and did not use personal protective equipment. Experimental studies were carried out using a tissue-equivalent phantom and thermoluminescent detectors LiF activated by Mg and Ti. The summary doses received by the alveolar are calculated. Results and discussion. The total dose of X-ray radiation to the alveolar ridge in the absence of shielding is 64, 38 and 16 Gy for 1.0, 1.5 and 2.0 cm thick lip, respectively. The obtained values of the absorbed doses with personal protective equipment indicate a high shielding ability of the lead rubber used in the clinic. The use of shielding devices for superficial radiotherapy of lower lip cancer can improve the quality of life, reduces the duration and severity of radiation damage.

The aim of the study was to evaluate the prognostic value of pSTAT3 expression in diffuse B-large cell lymphoma (DLBCL) in a Russian sample of patients. Material and methods. Retrospectively, the results of an examination of 50 patients with newly diagnosed DLBCL in the period from 2014 to 2017 were evaluated. Using immunohistochemical and morphometric methods, the relative number of tumor cells expressing pSTAT3 was determined. The relationship of various levels of marker expression with clinical and laboratory parameters was analyzed, and long-term results of patient therapy were evaluated. Results and discussion. The overexpression of pSTAT3 protein is associated with a non-GCB subtype of the disease, an advanced stage, the patients of 60 years and older age, as well as with a lower frequency of achieving complete remissions with DLBCL. Patients with a high degree of marker expression in tumor cells had lower rates of overall (OS) and progressive survival (PFS). It was revealed that the marker under study has good predictive ability, but is not an independent prognosis factor for DLBCL. Conclusions. The level of expression of pSTAT3 is an informative factor that allows predicting the response to standard therapy for diffuse B-large cell lymphoma. The indicated marker may be useful for identifying patients who need individualization of therapeutic tactics for this disease.

The defining feature of HER2/neu-positive Luminal B and HER2/neu-positive (non-luminal) subtype breast cancer is HER2/neu gene amplification and protein overexpression on cancer cell membrane. The HER2-targeted therapy is nowadays available for patients with HER2-positive breast cancer However, a significant fraction of HER2+ tumors acquire or possess intrinsic mechanisms of resistance, based on multiple factors, and genetic heterogeneity among them. The aim of our study was to quantify the heterogeneity of HER2/neu amplification in HER2/neu-positive Luminal B and HER2/neu-positive (non-luminal) subtypes of breast cancer. Material and methods. A retrospective analysis of 210 cases referred for dual probe fluorescence in situ hybridization (FISH) confirmation of an immunohistochemical equivocal 2+ result was performed. Results. Our results demonstrated a heterogeneous amplification pattern of HER2/neu gene, whose expression is a substantial cause of HER2/neu-positive Luminal B and HER2/neu-positive (non-luminal) subtypes of breast cancer, in 31 % of invasive breast cancer cases. As heterogeneous, we interpreted tumors containing cells with HER2/CEP17 ratio < 2 and gene copies 4 ≤ HER2/neu < 6, that is, those without HER2/neu amplification. The amount of heterogeneous tumors between HER2/neu-positive Luminal B and HER2/neu-positive (non-luminal) subtypes was not statistically significant. ROC analyses identified optimal cutoff point for HER2/CEP17 ratio as 2.6 for distinguishing heterogeneous tumors. Conclusion. The heterogeneity of HER2/neu amplification is determined by FISH in 31 % of cases and is independent of molecular breast cancer subtype. If a HER2/neu-positive breast cancer has HER2/CEP17 ratio ≤ 2,6, it contains minor subclones without HER2/neu amplification with a probability of 95 %. Our results demonstrated that HER2/neu amplification heterogeneity may be important for prognosis of survival and treatment decisions.

Detachment of the choroid during glaucoma surgery is the most common complication associated with depressurization or decompression of the eyeball. The emergence of this process is due to the peculiarities of the structure and relationships of the vascular and scleral membranes of the eye. The relevance of the study of this pathological condition is due to the fact that the late detection and treatment of ciliochoroidal detachment leads to serious changes in the organ of vision. This complication can complicate the postoperative period, change the results of the operation and increase the duration of rehabilitation, with different stages of glaucoma, and especially in the advanced stage. Therefore, knowledge of the etiology, pathogenesis, clinical picture of this process helps in finding a safe, timely and effective method of treatment and prevention of this complication. At present, the main signs of ciliochoroidal detachment, characteristic of this condition and features of the differential diagnosis of vascular detachment with choroidal tumors, hemorrhages and retinal detachment, are quite clearly known. The frequency of development of ciliochoroidal detachment directly depends on the level of the intraocular pressure gradient during the operation, and in the early postoperative period. The methods of reducing the risk and the tactics of treatment of the resulting complications are known. Nevertheless, many unresolved questions concerning the causes of ciliohoroidal detachment remain; there are different approaches to the tactics of treatment of these patients.

Attitude to health is a complex of social and medical aspects that reflect the subjective health self-assessment of (SZ) by the population, awareness of risk factors (RF) of non-communicable diseases, as well as the level of population involvement in the process of health promotion. A separate category among these parameters is the health self-assessment as an indicator that closely correlates with the human physical health. The aim of the study was to determine the gender characteristics of self-assessment of health status in the open population of the mid-urbanized city of Western Siberia. Material and methods. An one-time epidemiological study was conducted as part of cardiac screening for an open urban population of 25-64 years old among males and females of working age (on the model of Tyumen). The study of health self-assessment, physical complaints, as well as health care evaluation was conducted using a standard questionnaire WHO «MONICA-psychosocial» «Knowledge and attitude to own health». Results. In the open population of the middle urbanized city of Western Siberia, the extremely low men health self-assessment, compared with women, prevails in the older group of 55-64 years old. In the female population the negative health self-assessment and physical complaints totally prevail in young and mature age. Approximately 10 % of the Tyumen population determined adequate own health care (predominantly women of 35-44 years old); men aged 25-34 show a greater desire for own health care. Conclusion. A subjective-objective indicator of the population health, where the health self-assessment holds a unique position, requires active study in populations and can serve as a scientific basis for the development and formation of socially oriented preventive programs that take into account gender and age characteristics and risks.