ORIGINAL RESEARCH
Inroduction. Systemic inflammatory response (SIR) is an obligatory manifestation of operational stress affecting the functional status of patients, which is important to consider in persons with comorbid pathology.
Aim. Evaluation of the relationship between pulmonary volemia and SIR indicators in patients with comorbidity of chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IHD) after coronary artery bypass grafting (CABG).
Materials and methods. The study included 76 IHD patients aged 53 to 77 years who underwent CABG. Among the surveyed, 2 groups were identified: 39 patients with IHD and 37 – with a combination of IHD and COPD. The following indices were measured by transpulmonary thermodilution: pulmonary blood volume (PBV), extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), pulmonary shunt fraction (Qs/Qt). Determined the concentration in the blood of interleukin 6 and 10 (IL-6, IL-10), tumor necrosis factor-alpha (TNF-α); transforming growth factor-beta1 (TGFβ1), NLR - the ratio of neutrophils to lymphocytes; PLR – the ratio of platelets to lymphocytes.
Results. The most pronounced disturbances in the water balance of the lungs, manifested by an increase in EVLWI, PVPI and Qs/Qt were recorded in patients with comorbidity of COPD and IHD immediately after withdrawal from cardiopulmonary bypass. The PBV level at all measurement points in patients with COPD was lower, which indicated the prevalence of right ventricular failure. SIR on operational stress in this category of patients was manifested by the discoordination of the cytokine profile: a sharp increase in the concentration of IL-6 and IL-10 against the background of a relatively stable level of TNFα and TGF-β1, as well as an increase in NLR and PLR.
Conclusion. The unidirectional response of pulmonary volemia and SIR indicators to operational stress indicates the pathophysiological relationship of the studied phenomena.
Aim. To determine the adherence to treatment of patients with arterial hypertension (AH) and chronic obstructive pulmonary disease (COPD) against the background of complex therapy.
Materials and methods. We examined 56 patients with stage II hypertension in combination with COPD. Men accounted for 70%, women – 30%. The average age of patients is 52.9±0.46 years. The patients were prescribed a fixed combination of antihypertensive drugs – telmisartan 40 mg with amlodipine 5 mg and COPD therapy according to GOLD. Patients of group 1 (n=30) studied at a health school against the background of drug treatment, patients in group 2 (n=26) did not attend a health school.
Results. After 6 months of treatment, the number of patients in group 1 increased (p=0.001) regularly taking antihypertensive drugs, 96.7% of patients began to independently control blood pressure and keep a diary of a patient with hypertension. Patients of group 2 showed a statistically significant increase in the level of awareness of the presence of the disease and the awareness of patients about the risk factors for the development of the disease (p=0.01), although the number of patients controlling blood pressure remained low (p=0.1). In group 1, there was a positive trend in terms of the main risk factors, in group 2 the frequency of the prevalence of risk factors practically did not change. By the 6th month of therapy, all patients in group 1 achieved the target blood pressure, in group 2 – in 73.1% of patients. By the end of the observation, in patients of group 1, against the background of the chosen treatment tactics, there was a significantly more significant decrease in left ventricular mass index (LVMI) with its normalization in 33.3% of patients, indicating regression of LV hypertrophy (p=0.01), as well as a significant increase in the ratio of peak velocities on the mitral valve (E/A), (p=0.01), indicating an improvement in LV diastolic function. In group 2, antihypertensive therapy showed a moderate decrease in LVMI (p=0.1) with normalization of this indicator in only 2 (7.7%) of patients. By the 6th month of treatment, an improvement in the parameters of bronchial patency was revealed, however, in the 2nd group of patients, the changes in these parameters were statistically insignificant.
Conclusion. The effectiveness of the treatment of hypertension and COPD depends not only on the choice of the optimal treatment tactics, but also on the patient's compliance with the prescribed therapy regimen. The results obtained indicate a positive effect of the chosen complex treatment regimen on the functional parameters of the left ventricle and bronchial patency.
Introduction. TRPM8 has been implicated in the development of bronchial hypersensitivity to cold and is considered a potential target for computer-generated drugs.
Aim. Development of a strategy for the selection of ligands for TRPM8 by in silico methods.
Materials and methods. Using machine learning tools based on deep neural networks and further verification by intermolecular docking, a strategy has been proposed for predicting potential ligands for TRPM8, which consists in using a neural network to screen out potential drug candidates and thereby reduce the list of candidate ligands for verification using AutoDock program, which allows assessing the affinity of a protein for a ligand by the minimum binding energy and identifying possible conformations of a ligand upon binding to certain centers (amino acid residues) of a protein. The latter were used: Y745 (tyrosine 745 is a critical center for TRPM8), R1008 (phenylalanine 1008) and L1009 (alanine 1009).
Results. Of the 10 potential ligands predicted by the neural network, eight showed a high minimum binding energy and a greater number of conformations compared to the classic TRPM8 ligand, menthol, when verified by the AutoDock program. The two predicted ligands did not show the ability to interact with TRPM8, which may be due to insufficient allocated memory of the computing device for successful docking or other technical problems.
Conclusion. The proposed strategy is universal; it will accelerate the search for ligands for various proteins and will facilitate the accelerated search for potential drugs by in silico methods.
Introduction. An important part in the rehabilitation treatment of patients with asthma associated with obesity is the ambulatory-polyclinic stage of rehabilitation that includes drug and physiotherapeutic treatment. Recently, dry carbon dioxide baths (DCDB) are increasingly used.
Aim. is to assess the clinical and immunological efficiency of DCDB in the complex rehabilitation treatment of patients with asthma and obesity at the ambulatory-polyclinic stage of rehabilitation.
Materials and methods. The study included 60 patients with asthma and obesity admitted to the departments of medical rehabilitation and clinical examination of scientists of the Medical Association of FEB RAS. Patients of the main group (30 subjects) received DCDB and drug therapy. Patients of the comparison group (30 subjects) received only drug therapy. The DCDB procedures were carried out using the “Reabox” device at CO2 concentration of 15-20%, a temperature of 28-30ºC, 10 procedures. The changes in symptoms, ACQ-5 test, and respiratory function were assessed. The parameters of cellular immunity CD3+, CD4+, CD8+, CD16+, CD19+ and the levels of tumor necrosis factor (TNFα), interleukins (IL) IL-2, IL-4, IL-6, IL-10, IL-17A in the blood were analyzed.
Results. The achievement of asthma control took less time in patients of the main group. The improvement of bronchial patency was evidenced by the positive dynamics of spirometric indices. After DCDB therapy, an increase in suppressive activity of the cellular immunity, a decrease in the levels of pro-inflammatory cytokine IL-4, IL-17A were revealed. The TNF-α/IL-10 ratio statistically significantly changed due to the increase in the level of anti-inflammatory cytokine IL-10. In the comparison group, the positive dynamics was less pronounced.
Conclusion. The use of DCDB increases the clinical and immunological efficiency of the rehabilitation of patients with asthma and obesity at the ambulatory-polyclinic stage. The clinical effect is associated with immunocorrective action, which allows achieving control of the disease in a shorter period of time.
Aim. To assess the influence of the climatic and weather patterns at the South Coast of Crimea (SCC) on the effectiveness of health resort medical rehabilitation of patients with lung diseases (LD).
Materials and methods. A study carried in a group of 197 patients with LD. The influence of climatic and weather patterns at the SCC were assessed using the methods developed by the Academician Research Institute of Physical Methods of Treatment, Medical Climatology and Rehabilitation named after I.M. Sechenov – modified clinical index on weather pathogenicity and medical rehabilitation assessment according to the criteria of the “International Classification of Functioning, Disability and Health” (ICF).
Results. Regression equations for the dynamics of the ICF domains b280, b430, b4303 and for the mean value of all domains on the values of air temperature, wind speed, cloudiness, and air temperature variability have been developed, which allow to reliably form a rehabilitation prognosis for patients with LD for all terms of health resort treatment in the SCC.
Conclusion. The use of modernized clinical indices of weather pathogenicity allows one to adequately assess and predict the effect of weather dynamics and form a rehabilitation prognosis for patients with LD.
Introduction. The development of chronic allergic inflammation of the respiratory tract is determined by various genes. It is assumed that the clinical features of the course of bronchial asthma may be associated with singlet polymorphism of the vitamin D receptor.
Аim. To analyze the frequency of occurrence of polymorphic variants of the VDR-63980G>A gene and evaluate their association with the features of the development and course of bronchial asthma in children.
Materials and methods. To study the association of the VDR-63980G>A gene polymorphism with bronchial asthma in children, 154 patients with bronchial asthma aged 1 to 18 years and 116 healthy subjects were selected. The objective status of the patients was assessed with the clarification of the anamnesis, standard laboratory and instrumental examination. Single nucleotide substitutions were typed by polymerase chain reaction with real-time detection of the results. The genotype distribution was evaluated using the “Gen-Expert” program.
Results. As a result of the association analysis, the relationship of VDR-63980G>A with bronchial asthma in children was established. The presence of genotype -63980AA of the VDR gene increases the risk of developing bronchial asthma in a child by 1.85 times (OR=1.85, [CI 1.02-3.38]; χ 2=4.22, p=0.04). The homozygous genotype -63980GG was more common in the control group – in 49.5% versus 45.4% against the sick children. The genotype of the minor homozygote -63980AA is associated with the early onset of the disease, pronounced obstructive pulmonary ventilation disorders.
Conclusion. The association of genotype -63980AA of the VDR gene with the risk of asthma development in preschool children was revealed.
Introduction. The diagnosis of asthma presents objective difficulties in children aged less than 5 years. Not all children with recurrent virus-induced obstruction can further develop asthma.
Aim. To assess the realization of different clinical and pathogenetic variants of bronchoobstructive syndrome in the child population.
Materials and methods. Risk factors of 75 patients with bronchoobstructive syndrome in the first 5 years of life were retrospectively evaluated. 57 patients were surveyed using the “Asthma Prediction Tool” questionnaire. At the end of the follow-up period (one year), cases of bronchial asthma were evaluated.
Results. A predictive contribution to the implementation of the recurrent variant of bronchoobstructive syndrome has a burdened hereditary allergic anamnesis (OR=5,4, CI 1,79-16,46, p<0,05) and the presence of atopic dermatitis (OR=7,7, CI 2,73-21,95, p><0,05). Symptoms of allergic rhinitis in combination with hypertrophy of the Palatine tonsils in 6,06 and 3,45 times, respectively, increase the risk of bronchial asthma (p><0.05). Conclusion. As a result of research, there are significant factors in the implementation of bronchial asthma such as concomitant allergic diseases in combination with a hereditary background and hypertrophy of the palatine tonsils. The>˂ 0,05) and the presence of atopic dermatitis (OR=7,7, CI 2,73-21,95, p˂ 0,05). Symptoms of allergic rhinitis in combination with hypertrophy of the Palatine tonsils in 6,06 and 3,45 times, respectively, increase the risk of bronchial asthma (p˂ 0.05).
Conclusion. As a result of research, there are significant factors in the implementation of bronchial asthma such as concomitant allergic diseases in combination with a hereditary background and hypertrophy of the palatine tonsils. The “Asthma Prediction Tool” questionnaire allows you to predict the development of bronchial asthma in patients with episodic and recurrent bronchial obstruction. The article will be useful for both pediatricians and primary care professionals, as it allows to rationally influence the risks of bronchial asthma formation.
Introduction. Kamchatka Krai is a region with low population density and poorly developed industry. However, in large cities the air quality is degraded due to economic activity. Aim. To study the concentration of airborne particulate matter (in particular, up to 1 µm and up to 10 µm) in Petropavlovsk-Kamchatsky and Yelizovo air and carry out a comparative analysis with the previously obtained results of environmental monitoring of atmospheric suspension.
Materials and methods. Airborne particulate matter was studied in snow which was collected during snowfalls to avoid its secondary pollution by anthropogenic aerosols. The melted snow was analyzed on a Fritsch Analysette 22 NanoTech laser particle analyzer (Germany).
Results. PM1 particles were found in five snow samples taken in Petropavlovsk-Kamchatsky. The quantity of PM₁₀ is low in all samples, and only in two of six sampled areas it reaches 12%. Compared to the results of previous studies, the concentration of PM1 is at the same level as in previous years, and the content of PM₁₀ has decreased. In samples from Yelizovo, the same trends are observed. Compared to 2018, when a high concentration of PM₁₀ particles was found in almost all samples, reaching 57.2%, there is a trend towards a decrease in the concentration of the potentially hazardous PM fraction.
Conclusion. Updated data on the particle size distribution of airborne particulate matter in two cities of the Kamchatka Peninsula were obtained. In the snow samples collected in Petropavlovsk-Kamchatsky and Yelizovo, we found PM₁ and PM₁₀ particles hazardous to human health, although their concentration is generally lower than in previous years of the study.
Aim. The study of various indicators of endotoxicosis, including lymphological, with gangrene of the lungs.
Materials and methods. The study group consisted of 21 adult patients with extensive and limited pulmonary gangrene, who were drained of the thoracic or right lymphatic ducts for the treatment of endotoxicosis with subsequent lymphosorption and lymph reinfusion. The control group included 22 adult patients with pulmonary abscesses in the convalescent stage, for whom the right or thoracic lymphatic ducts were drained for therapeutic purposes, followed by lymphosorption and lymph reinfusion for 3 days. The main clinical parameters were studied: the intensity of cough and the daily volume of excreted sputum, its ichorous smell, pain at the site of pathology, body temperature, pulse, respiratory rate, liver size, sleep and appetite. The laboratory parameters were determined – in the blood tests, leukocytosis, toxic granularity of neutrophils, and the leukocyte index of intoxication were detected. Studied the number of molecules of average weight in the blood and lymph. New methods for the diagnosis of endotoxicosis were developed and applied, based on indicators of extravascular fluid of the lungs and indicators of continuous measurement of the volumetric flow rate of lymph flow from the lymphatic ducts.
Results. Pulmonary gangrene is accompanied by severe and extremely severe de grees of endotoxicosis, while the indices of endotoxicosis in the lymph are significantly higher than in the blood. The greatest parameters of endotoxicosis in pulmonary gangrene were determined in the lymph of the right lymphatic duct, which drains 2/3 of the pulmonary lymph. When draining the right or thoracic lymphatic ducts with gangrene of the lungs, the most accurate method for the study of endotoxicosis is the priority method of continuous measurement of the volume rate of lymph flow, taking into account the back pressure of the venous blood pressure.
Aim. To assess the change in the lipid-synthesizing function of the liver in congenital cytomegalovirus infection (CMVI) in dead newborns.
Materials and methods. The study of the lipid spectrum of umbilical cord blood in the first minutes of life was carried out in 59 full-term newborns with antenatal ontogenesis, unburdened and burdened with congenital CMVI. The first group consisted of 25 newborns of early neonatal age (control group) from mothers without moderate and severe obstetric and somatic pathology, as well as respiratory viral diseases and sexually transmitted infections. The second group included 18 children of the same age (comparison group), whose mothers suffered exacerbation of CMVI in the second trimester of pregnancy, which did not lead to antenatal viral aggression. The third group was represented by 16 newborns with congenital CMVI. The life expectancy of children was 2-5 days. In the first group, the main cause of death of children was prolonged ante- and intranatal hypoxia, atelectasis and hyaline membranes of the lungs, in the second group – prolonged antenatal hypoxia, intranatal hypoxia and atelectatic, hyaline and edematous-hemorrhagic pneumopathies, and in the third group – congenital CMVI, which manifested itself as cerebral ischemia of moderate and severe degree, meningoencephalitis, ventriculomegaly, pseudocysts of the vascular plexus and subarachnoid hemorrhages, monocytosis, vesiculopustulosis, hepatitis and pneumonia. In the blood serum from the umbilical vein during biochemical analysis, the concentration (mmol/L) of total cholesterol, high-density lipoproteins, low-density lipoproteins and triglycerides was estimated.
Results. In newborns of the second group in the blood serum from the umbilical cord vein, the concentration of total cholesterol was 1.90±0.04 mmol/L, high-density lipoproteins – 1.49±0.06 mmol/L, low-density lipoproteins - 0.26±0,02 mmol/L and triglycerides – 0.49±0.03 mmol/L (in the first group, respectively, 1.93±0.06 mmol/L, p>0.05; 1.37±0.06 mmol/L, p>0.05; 0.43±0.02 mmol/L, p<0.001; 0.45±0.02 mmol/L, p>0.05). In the third group, compared with the second one, there was a decrease in the level of total cholesterol to 1.79±0.04 mmol/L (p<0.05) and high-density lipoproteins – to 1.28±0.06 (p><0.05) against the background of an increase in triglyceride concentration up to 0.59±0.03 mmol/L (p><0.05). Conclusion. The above changes in the lipid-synthesizing function of the liver indicate a direct and indirect effect of congenital CMVI on the morphological structure of hepatocytes and the activity of enzyme systems. Key words: full-term newborns, congenital cytomegalovirus infection, total cholesterol, high-density lipoproteins, lowdensity lipoproteins, triglyceride>˂ 0.05) and high-density lipoproteins – to 1.28±0.06 (p<0.05) against the background of an increase in triglyceride concentration up to 0.59±0.03 mmol/L (p><0.05). Conclusion. The above changes in the lipid-synthesizing function of the liver indicate a direct and indirect effect of congenital CMVI on the morphological structure of hepatocytes and the activity of enzyme systems. Key words: full-term newborns, congenital cytomegalovirus infection, total cholesterol, high-density lipoproteins, lowdensity lipoproteins, triglycerides>˂ 0.05) against the background of an increase in triglyceride concentration up to 0.59±0.03 mmol/L (p˂ 0.05).
Conclusion. The above changes in the lipid-synthesizing function of the liver indicate a direct and indirect effect of congenital CMVI on the morphological structure of hepatocytes and the activity of enzyme systems.
SELECTED REPORTS
Aim. Demonstration of a case of diagnosing extranodal diffuse large B-cell lymphoma of rare localization – with a massive lesion of the cervix with spread to the body of the uterus and the anterior wall of the vagina.
Results. The patient, born in 1991, considers herself ill since December 2020, when watery, bloody discharge from the genital tract first appeared. She went to the gynecologist at the place of residence; upon examination, a malignant neoplasm was suspected. For further examination and treatment, she was sent to the Amur Regional Oncological Dispensary, where a morphological and immunohistochemical study of the biopsy material was performed. In a histological specimen, there is a picture of lymphoma. Immunohistochemical study: tumor cells express CD10, CD20, BCL6, CD23. Tumor cells do not express CD5 (+ on small T-lymphocytes), BCL2 (+ on small T-lymphocytes), CD30, C-MYC, MUM1. When reacting with Ki-67, 90% of tumor cells are positive. The morphoimmunohistochemical picture is characteristic of diffuse large Bcell lymphoma from cells of germ cell centers.
Conclusion. Diagnosis of extranodal lymphoma can be very difficult, and the leading role belongs to an experienced morphologist and the availability of modern diagnostics of the variant of lymphoma.
REVIEWS
The article provides a brief review of the PubMed and Google Scholar databases on the clinical and immunological features of the course of the COVID-19 in pregnant women caused by SARS-CoV-2. The significance of physiological changes in the body of a pregnant woman, namely, an increase in the metabolic rate and oxygen consumption, a decrease in the functional residual capacity, in the adaptability of the immune response in pregnant women to infection is shown. The factors are described that allow pregnant women to be included in the risk group for the development of a COVID-19, such as a decrease in the immune response due to a semi-allogeneic fetus, preeclampsia, as well as a cytokine storm during the pro-inflammatory period of pregnancy. The analysis of the world literature data concerning the clinical and immunological features of the new coronavirus infection in pregnant women made it possible to conclude that the issue of developing an effective method for modulating the immune response by the body of a pregnant woman is insufficiently studied.
Introduction. The global spread of SARS-CoV-2 coronavirus infection worldwide determines the need to study the clinical features, complications, extrapulmonary manifestations and long-term consequences of the infection in children. While many studies have been described in adult patients, there are limited data analyzing the clinical course of the disease in pediatric patients infected with SARS-CoV-2. Aim. Review of the literature containing currently reported cases of SARS-CoV-2 infection in children to present the state of the art, understand the direction of research and unresolved issues. Materials and methods. An analysis of publications containing data from studies of SARS-CoV-2 cases in children was carried out. Results. Researchers from different countries agree that children are less susceptible to COVID19. This can create a dangerous situation, which can lead to a weakening of attention to children. Although their clinical manifestations are mainly mild to moderate symptoms, nevertheless, severe cases of the disease occur in children, which can lead to death. Conclusion. The complexity and variability of COVID-19 manifestations support the hypothesis that further research is needed on the long-term and chronic symptoms of COVID-19 in children. Failure to understand the underlying biological mechanisms behind these persistent symptoms increases missed opportunities to identify patients at risk of chronicity in order to prevent such conditions and seek rehabilitation approaches for children with COVID-19.
Chronic inflammatory diseases of the respiratory tract, including asthma and chronic obstructive pulmonary disease, are a global problem of our time due to the widespread prevalence and difficulty of controlling the course. The mechanism of chronic inflammation in the bronchopulmonary system is closely related to metabolic disorders of lipids and their derivatives. Lipids and their mediators play both a pro-inflammatory and anti-inflammatory role in chronic inflammatory bronchopulmonary pathology. In particular, free fatty acids (FFAs) perform important signaling and regu latory functions in the body, coordinating metabolic and immune relationships. The mechanism that potentially binds FFAs and inflammatory reactions involves the activation of their receptors (FFAR – free fatty acid receptor), which are expressed on the cells of the respiratory tract, as well as on nerve and immune cells. Currently, FFARs are considered attractive targets in the treatment of chronic bronchopulmonary pathology, since modulation of their activity through the use of alimentary polyunsaturated fatty acids (PUFA) can affect the activity and resolution of neuroimmune inflammation in the bronchopulmonary system. However, controversial issues regarding their effectiveness and dose standardization of PUFA continue to limit their widespread use. This review summarizes the literature data on the role of medium- and longchain FFAs in the body’s immunoregulation in normal conditions and in chronic bronchopulmonary pathology. Data on medium and long chain FFA receptors – FFAR1 and FFAR4, FFAR-mediated signaling pathways in the regulation of metabolism and immune responses are systematized. The perspective and complex issues of the use of fatty acids in the treatment of chronic bronchopulmonary pathology are discussed.
Aim. A brief analysis of scientific publications on the role of prostaglandins at early stages of embryonic development has been carried out.
Results. In the process of studying the literature data, both national and, for the most part, foreign authors, the role of prostaglandins was established as paracrine factors involved in an increase in vascular permeability and angiogenesis, mediating the effect of gonads and the expression of growth factors (vascular endothelial growth factor, angiopoietin) during implantation and decidualization. The effects of prostaglandins on the degradation and remodeling of the extracellular matrix of the uterus are described. The role of prostaglandins in the transportation of gametes and embryos is shown. Information on the role of prostaglandins in the growth and development of blastocysts, as well as trophoblast invasion, is presented.
Conclusion. The understanding of the role of prostaglandins at the early stages of embryonic development is far from complete. Despite active research in this direction, scientists still have many questions regarding the mechanisms of action, the functions of prostaglandins at the initial stages of embryogenesis. Most of the information has come from animal studies, mainly rodents. Therefore, to further study the mechanisms underlying the diverse action of prostaglandins on multiple processes of embryogenesis, it is necessary to carry out additional studies in humans.
Aim. The analysis of scientific publications on the treatment of malignant neoplasms, the effect of antitumor therapy on the morphofunctional state of the gonads is carried out.
Results. Treatment of malignant neoplasms is often accompanied by side effects that directly depend on the patient’s age, type of cancer, treatment regimen and doses, which has put forward a new urgent problem – the state of health and quality of life during remission of cancer or after recovery from it. Thus, cytostatically induced testicular damage leads to reproductive dysfunction in men on the “pre-testicular” (central nervous system and the peripheral nervous system, pituitary gland), “testicular” (gonads), “post-testicular” (epididymis, etc. organs of the genitourinary system involved in spermogenesis) levels of the reproductive system, which is especially important against the background of a sharply declining fertility of the modern male population. Accordingly, understanding the regularities of the processes of reparative regeneration of damaged tissues is important for the development of rehabilitation programs, the preservation of reproductive function and quality of life in patients who have undergone cytostatic therapy, especially in young people.
Conclusion. The literature review covers epidemiological and experimental data on the effects of chemotherapy on spermatogenesis.