REVIEWS
Reconstruction of the anterior cruciate ligament (ACL) is a fairly successful surgical intervention that can achieve satisfactory results in 75-97 % of cases. In order to show the main categories of factors that can affect the functional outcomes of patients after ACL reconstruction and lead to unsatisfactory outcomes after surgery based on the literature data, we have run a search for English- and Russian-language publications in the electronic databases PubMed and RSCI for the period from 2000 to 2019 using the keywords: anterior cruciate ligament, ACL, revision, re-reconstruction, re-injury, re-rupture, graft failure. Out of 634 papers, 113 publications with the full text were selected. Inclusion criteria - more than 50 cases in the report; follow - up period of more than 2 years; the same groups of patients; assessment of knee joint function; application of various imaging options for the knee joint. 26 papers were included in this review. Based on the analysis of the multiple causes of failed ACL reconstruction outcomes were merged into four main groups: technical mistakes diagnosis and surgery (from 22 % to 79 %); re-injury (18 % to 79 %); biological factors (violation of the integration of the graft and its ligamental) (17 %); errors of rehabilitation and other (15 %). Thus, the review made it possible to systematize the causes of unsuccessful outcomes of ACL reconstruction and identify the most frequent.
The scientific review analyzes publications that prove the positive effects of bioactive lipids on human health. It is noted that certain lipids have a prophylactic effect on the body and can inhibit the development of certain diseases. The increased speed of passage of food masses after bariatric surgery affects the completeness of lipid breakdown and absorption in the stomach and small intestine. In case of significant violations, this can cause some complications in the operated patients. The effect of bioactive lipids on the metabolism of obese patients and the possibility of including lipids in the postoperative diet were analyzed.
BIOMEDICINE
Under certain conditions, both activators and inhibitors of Nrf2-dependent signaling and autophagy can serve as potential agents for the prevention, treatment, and maintenance therapy of cancer, as well as overcoming chemoresistance. We are developing a panel of structurally related synthetic monophenolic compounds, in addition to a direct antioxidant effect, having the ability to affect intracellular signaling pathways and processes, including the above mentioned. Aim of the study was to investigate the relationship between its structure and the ability to influence the expression of autophagy and Nrf2 pathway genes.
Material and methods. Five original hydrophilic phenolic structurally related compounds were synthesized; the prototypical inductor of the Keap1/Nrf2/ARE system, monosubstituted phenol tert-butylhydro-quinone (tBHQ), served as a reference substance. We used cultures of murine Lewis lung carcinoma (LLC) and human breast adenocarcinoma MCF-7 cells, with the test compounds at a concentration of 20 gM cells were incubated for 24 hours. Changes in mRNA expression of Nrf2, Nqo1, LC3b, and Sqstm1 genes encoding Nrf2, NAD(P)H:quinone oxidoreductase-1, LC3B, p62/sequestosome-1, respectively, were determined by TaqMan real-time PCR.
Results and discussion. Structurally related synthetic monophenols effectively induced the Keap1/Nrf2/ARE system in LLC and MCF-7 cells, increasing the expression of the Nrf2-driven Nqo1 gene, and ambiguously affected the transcription of genes of proteins mediating autophagy: the content of mRNA of the LC3B protein did not change, while the expression of mRNA of the p62 protein, which affects the operation of both systems (processes), is increased only by the action of ortho-monosubstituted phenol with an «active» sulfur atom in the para-propyl substituent TS-13 and its structural analogue TS-12 with a para-substituent shortened by one methylene. It can be assumed that the observed effect either indicates the ability of TS-13 and TS-12 both to induce the Keap1/Nrf2/ARE system and to stimulate autophagy, or reflects a compound-mediated mutually reinforcing cross-activation of these processes.
Bacterial purulent meningitis (BPM) is one of the most severe infectious and inflammatory diseases of the nervous system, which is characterized by high mortality and frequent development of residual neurological deficits. Edema and swelling of the brain is the most common cause of death in patients with neuroinfections. Most often, brain edema develops in pneumococcal meningitis (PM), which has the highest mortality rate among all bacterial meningitis. The aim of our work was to study the effect of new derivatives of 3-hydroxypyridine, 2-ethyl-6-methyl-3-hydroxypyridinium 2.6-dichlorophenyl (amino)phenylethanoic acid (EMHDA) and bis(2-ethyl-6-methyl-3-hydroxypyridinium) 2.6-dichlo-rophenyl (amino)phenylethanoic acid (B-EMHDA), on the degree of brain edema in the simulation of BPM in experimental conditions.
Material and methods. BPM was modeled by injecting a suspension containing Streptococcus pneumoniae at a concentration of 5 x 109 CFU/ml into the subarachnoid space of the brain. The degree of severity of cerebral edema in rats was assessed by determining the content of total water, free and bound fractions in the brain tissue, as well as the hydration coefficient. The lower the hydration coefficient, the more pronounced the cerebral edema. Determination of the content of water fractions in brain tissue and blood was carried out by the thermogravimetric method.
Results and discussion. 24 hours after the induction of meningitis, the free water content increases and the amount of bound water decreases. That testifies to the development of cerebral edema. Hydration coefficient in the group treated with EMHDA at a dose of 50 mg/kg, increased by 11.5 % relative to the control group; in the group receiving EMHDA at a dose of 25 mg/kg, increased by 15.3 % compared to the control group (p<0.05). Hydration coefficient in the group treated with B-EMHDA at a dose of 50 mg/kg, increased by 23 % relative to the control group; in the group receiving B-EMHDA at a dose of 25 mg/kg, increased by 26.9 % compared to the control group; and the group receiving B-EM-HDA at a dose of 12.5 mg/kg was 19.2 % higher relative to the control group (p<0.05).
Conclusion. Brain edema is least pronounced when using B-EMHDA at all three studied dosages - 50, 25 and 12.5 mg/kg. Injection of EMHDA at doses of 50 mg/kg and 25 mg/kg also helped to reduce the degree of brain edema when modeling BPM in experimental conditions.
The frequency of recurrent miscarriage among all desired pregnancies is 2-5 %. The important role of immune disorders in early termination of pregnancy has been proven. Elucidation of the nature of differentiation of B-lymphocytes in women with threatened miscarriage and habitual miscarriage in the anamnesis seems relevant, since it will clarify the immune mechanisms of the pathogenesis of this pathology. Aim of the study was to assess the nature of differentiation and type of the cytokine-producing function of peripheral B lymphocytes in women with a threatening spontaneous miscarriage and recurrent miscarriage in history.
Material and methods. Pregnant women aged 18-40 years at a gestation period of 5-12 weeks were examined. The main group consisted of 60 pregnant women with a threatening spontaneous abortion at the time of the examination and a history of recurrent abortion. 35 pregnant women with uncomplicated pregnancy were examined as a control group. The comparison group consisted of 25 primary pregnant women with threatened spontaneous abortion at the time of the examination. The material for the study was peripheral venous blood. Subpopulations of B lymphocytes CD20+CD5+, CD20+CD5-, CD19+IgD+, CD20+IgM+, CD20+IgG+; CD19+CD20-CD38+, CD19+CD27-, CD19+CD27+, CD19+IgD+CD27+, CD19+IgD+CD27-, CD20+IL-4+, CD20+IL-6+, CD20+IL-10+ were determined by the method of flow cytometry.
Results and discussion. In the main group, an increase in the proportion of B cells in the peripheral blood was recorded, mainly due to B2 lymphocytes, CD20 +IgM+ lymphocytes and memory cells, along with a decrease in the level of naive cells and plasma cells, as well as lymphocytes spontaneously expressing IL-6 and IL-10. Thus, the threatening habitual miscarriage is associated with a shift in B-lymphocyte differentiation towards immature forms. A decrease in the number of CD20+IL-10+ cells in patients of the main group can lead to a weakening of the suppressor associated with IL-10 and subsequent impairment of the maternal organism’s tolerance to a semi-allogeneic fetus. Similar changes in the differentiation and functional activity of B-lymphocytes were also observed with a threatening loss of the first pregnancy, which may indicate a single mechanism for the development of a threatening spontaneous miscarriage, the severity of which increases with repeated loss of pregnancy.
PHYSIOLOGY
Objective: to specify changes in functional reserves of hemodynamics and heart rate variability at performing active orthostatic test by migrants (0-th generation) and those born in the North in the 1st and 2nd generation, all residents of Magadan region.
Material and methods: 106 young males aged 17-21, permanently residing in the North, were examined. All the young men were divided into 3 groups: newcomer Caucasians (0-th generation) and people born to them in the region (in the 1st and 2nd generations). Readjustments in cardiorhythm and hemodynamics in response to the active orthostatic test were studied.
Results. At the resting state, young male examinees demonstrated their parasympathetic influence of the autonomic system on the heart rate regulation to increase from the 0th to the 2nd generation, which is observed together with more economical functioning of the cardiovascular system. In response to the orthostatic test, the 2nd generation subjects showed optimum autonomic support in hemodynamics by reducing the activity of the parasympathetic link which reflected the inhibition of vagal activity in order to moderately activate the sympathetic link of autonomic regulation.
Conclusion. We could observe optimization in cardiovascular system in each next generation in the North with the decrease in reactivity to active orthostatic test and the growth in the parasympathetic link of autonomic nervous system at rest.
CLINICAL MEDICINE
An experimental study of the innovative wound expander applicability for surgical operations in the oral cavity was performed. For comparative analysis, 40 experimental models were divided into 4 groups depending on the use of auxiliary devices: Farabef hooks, VICRYL 3/0 suture material (ETHICON, USA), innovative wound expander, without the use of additional materials and tools. An experimental simulation of the operation of dental implantation in the area of the included dentition defect (Kennedy class III, IV), as one of the most frequent outpatient surgical operations in the oral cavity, was performed. The results of the study prove the innovative wound expander applicability for surgical operations in the oral cavity and its obvious advantages over existing analogues: providing adequate access, reliable, stable fixation of the wound edges, minimal injury to the surrounding tissues, protecting the edges of the operating wound from possible injury during surgery, lightweight, durable design, individually adapted to the anatomical features of the operated area, made of biologically inert materials, safety and ease of operation, affordable price, no need for an assistant to contact the operating field. Therefore, it is reasonable to conduct further clinical approbation and introduce the device into the practice of dental surgeons and maxillofacial surgeons.
Atopic diseases remain one of the most common childhood diseases. At the beginning of life, atopic dermatitis (AD) occurs, and only then bronchial asthma (BA). This staged development of sensitization and transformation of clinical manifestations is called the atopic march. Are the genetic factors of predisposition to AD the same for BA? There is still no definite answer to this question. Mutations in the filaggrin gene (FLG) are known to impair skin barrier function. Filaggrin is expressed not only in the skin, but also in the respiratory organs of the nasal mucosa, lungs, and bronchi. Filaggrin defects lead not only to disruption of the skin barrier, but also to an increase in the Th2 response and increased production of IgE, typical of bronchial asthma. Therefore, mutations in the FLG gene can be a risk factor for the development of not only AD, but also BA.
The aim of this study was to compare the values of the association of mutations in the FLG gene with AD and BA in the Russian sample.
Material and methods. Case-control study design. We used 265 blood samples from children. 4 mutations in the filaggrin gene were identified by real-time PCR. The association of mutations with disease was assessed by odds ratio.
Results. We showed a strongly pronounced association of the deletion of 4 nucleotides (2282del4) with AD, but not with BA, although for patients with atopic BA the indicator of the association of this mutation with the disease was higher than for the group with symptoms of bronchial asthma identified by the ISAAC questionnaire. These results lead to the conclusion that the role of the filaggrin gene for BA is much less significant than for AD.
Burn injury and its consequences are an important medical and social problem, given the high mortality and disability rates. The leading cause of death in patients with extensive and deep burns is burn septicotoxemia.
Material and methods. The material was the heart muscle of the anterior, posterior and lateral walls of the left ventricle of those who died from burn disease during septicotoxemia. The control group included cases of male mortality as a result of “acute coronary death”. The study of the ultrastructure of endotheliocytes of blood capillaries of the myocardium has been carried out.
Results and discussion. Ultrastructural analysis of endotheliocytes of blood capillaries of the myocardium showed that in burn septicotoxemia, intracellular degradation processes are observed in the form of swelling of the cytoplasm and organelles, a decrease in the concentration of vesicular structures, as well as activation of autophagy due to the appearance of autophagosomes and autolysosomes in the cytoplasm. Activation of autophagy should be considered as a naturally developing compensatory reaction aimed at preserving the cellular pool of endotheliocytes of the blood capillaries of the myocardium in response to the alterative effect caused by burn septicotoxemia.
Conclusion. The obtained data can serve as a justification for the manifestation of left ventricular contractile insufficiency, which is a consequence of endothelial dysfunction and microcirculatory disorders in the myocardium in burn septicotoxemia.
Burn injury is an important medical problem, as it is accompanied by high mortality rates in burn shock. Aim of the study was to conduct an ultrastructural stereological analysis of changes in the blood microvessels of the left ventricular myocardium in burn shock.
Material and methods. Myocardial samples during the early section were collected 2 hours after the detection of biological death in the victims from severe burn shock (3 men and 2 women); age group 32-44 years. An ultrastructural study of endothelial cells of the microvasculature of the left ventricular myocardium was carried out.
Results and discussion. The development of severe burn shock is accompanied by changes in the ultrastructure of the endothelial cells of the blood microvessels of the left ventricular myocardium, which is associated with intracellular degradation and exocytosis. These ultrastructural changes may indicate impairment of vesicular transport in the endothelium of the myocardial microvessels in burn shock. A feature of the ultrastructure of the endothelium was the heterogeneity of the endothelial cells of the blood capillaries due to the revealed dark and light endothelial cells, which differ in the saturation of the cytoplasm with organelles. The new data obtained on changes in the ultrastructure of the endothelium of the microvasculature of the left ventricular myocardium can be informative in the development of approaches to intensive therapy of cardioprotective direction in combustiological patients with burn shock.
Pulmonary tuberculosis has a lot of clinical manifestations, and it complicates the diagnosis of tuberculosis in the general clinical practice. We studied the clinical manifestations of tuberculosis detected in the pulmonary department and compared them with the significancy of diagnostic methods.
Material and methods. People with a verified diagnosis of lung tuberculosis (n = 109) were examined using the GeneXpert MTB/RIF method if Ziehl Nielsen bacterioscopy has negative results or if there was no effect of treatment for two weeks.
Results. All patients had complaints of both intoxication and bronchitis as with pneumonia on admission. Infiltrative tuberculosis (57.1 %; n = 68), disseminated tuberculosis (16.8 %; n = 20) were most often diagnosed. We looked for correlations between dyspnea and the prevalence of the process (p = 0.24), dyspnea with temperature (p = 0.24), the presence of pain in the chest (p = 0.405), the results of immunodiagnostics and sputum examination (p = 0.133). We found out that there are no such correlations in tuberculosis. The term for diagnosing tuberculosis was 7.97 ± 3.9 days in the presence of cough with sputum and 9.04 ± 4.3 days in the case of dry cough. The term for diagnosing tuberculosis was 12.31 ± 4.9 days in patients without cough. Mycobacterium tuberculosis was detected using GeneXpert MTB/RIF molecular genetic methods with nonproductive cough in 84.5 % (60 people out of 71), while in the first days of hospitalization in 46.6 % of patients (28 people out of 60, p < 0.001).
Conclusion. It was found that the period of hospitalization is little related to the characteristics of patients and depends on organizational measures to identify mycobacterium tuberculosis. It is recommended to immediately apply the GeneXpert MTB/RIF method to patients with mild tuberculosis.
PREVENTIVE MEDICINE
The aim of the study was to study the etiological structure and epidemiological features of infectious diseases that occur with central nervous system damage in hospitalized patients.
Material and methods. A retrospective study of the medical histories of 376 patients with meningitis and encephalitis was conducted.
Results and discussion. At the pre-hospital stage, only 198 (52.6 %) patients were diagnosed with «meningitis, encephalitis», which indicates that primary care physicians are not sufficiently alert to diseases of the central nervous system (CNS). When studying the epidemiological history, contact with infectious patients was noted in 69 (18.3 %) patients. The structure of neuroinfections in hospitalized patients was dominated by meningitis (334 cases - 88.8 %), encephalitis was found in 42 (11.2 %) patients. Among meningitis, purulent processes (205 people - 61.4 %) prevailed over serous ones (127 patients - 38.0 %); 2 patients were diagnosed with mycotic meningitis. In adults, the etiology of the disease was clarified in 58 (44.6 %) of 130 patients with bacterial meningitis and in 22 (27.8 %) of 79 with serous meningitis; among children - in 60 (80 %) of 75 patients with purulent meningitis and in 23 (47.9 %) of 48 with serous processes. Encephalitis and meningoencephalitis were detected in 30 adult patients and 12 children. The etiology of encephalitis was established in 13 (43.35) adults and 4 (25 %) children.
HEALTHCARE MANAGEMENT
The purpose of this study is to conduct a medical and statistical analysis of disability indicators for the period 2009-2019 in the territory of the Republic of Tatarstan (RT) and to substantiate the main directions for improving rehabilitation measures.
Material and methods. The object of the study was the medico-statistical indicators of «Main Bureau of Medical and Social Assessment in the Republic of Tatarstan (Tatarstan)» of the Ministry of Labor of Russia for 20092019. The study was conducted using a retrospective design. On the basis of the obtained indicators, the absolute and relative values of indicators per capita were calculated. Also, the calculation of the intensive and extensive indicators was carried out. Time series were constructed and trends were evaluated using Mann-Kendall test.
Results and discussion. According to the results of the study, a reliable trend was revealed to increase the share of first-time disabled persons of the first group by 2.6 times in 2009-2019, which is consistent with similar indicators for the Russian Federation. Analysis of the structure of the causes of primary disability for 10 years showed that one of the main causes, along with cancer, was diseases of the cardiovascular system. It was revealed that during the study period, the indicator of the level of primary disability among citizens with circulatory system diseases (CSD) decreased by 2.5 times, but the share of disabled people of the first group in 2019, significantly increased compared to 2009 - by 3.7 times. It was found that the main causes of primary disability in the adult population with CSD in the Republic of Tatarstan were coronary heart disease and cerebrovascular diseases. On the basis of the obtained data, the necessity of improving the measures of state control over the implementation of rehabilitation programs, in particular medical rehabilitation, by expanding the functionality of the «Federal Register of Disabled People» is justified.
Conclusion. Given that the most important element of secondary prevention in persons recognized as disabled is pharmacotherapy, improving the tools for its rationality and quality is one of the priorities for improving the system of rehabilitation of persons suffering from CSD.
Aim of the study was to analyze the socio-economic determinants and prevalence of possibly presence CHD in residents of a large industrial region.
Material and methods. The study sample included residents of rural settlements of the Kemerovo region and districts of the city of Kemerovo. The study involved 1600 respondents aged 35-70 years. The determinants of socio-economic status (SES) were assessed: the level of education and income, professional affiliation, marital status / family composition, place of living.
Results. The majority residents of rural settlements (50.9 %) had a secondary vocational education, compared with urban residents (46 %). A high level of income (over 20 000 rubles) was observed 1.53 times more often among the urban population than rural population. It was revealed that one third (29.3 %) of the rural population is employed in agriculture, and about 40.4 % do work that does not require vocational qualification. Among residents of rural settlements, there are statistically significant more those marriage/living with a partner, than among urban residents (75.6 % versus 62.9 %, respectively). The SES analysis of the study participants with possibly presence CHD indicates a predominant share (50.9 %) of vocational secondary education and medium income level (48.9 %). It was revealed that among the lonely rural residents possibly presence CHD occurred 10.0 % more often (urban 26.7 %, rural 36.7 %, p = 0.035) than among those living in the city.
Conclusion. In the Kemerovo Oblast CHD possibly presence is more common in women, depending on socio-economic determinants it is more often observed in persons with a secondary vocational education and medium income level, equally among both skilled and low/ unskilled workers living with partner in urban settings.
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