REVIEWS
Type 1 diabetes mellitus (DM) is one of the most prevalent endocrinological disorders of childhood. This disorder is accompanied by numerous micro- and macrovascular complications that reduce children’s life expectancy and increase healthcare costs. Central nervous system (CNS) damage in children and adolescents with type 1 DM is a fairly common but poorly studied complication. The leading role among CNS changes is played by cognitive dysfunction (CD). The pathophysiological aspects of CD in type 1 DM haven’t yet been understood completely. The three main triggers are hypoglycemia, chronic moderate hyperglycemia, and acute hyperglycemia (diabetic ketoacidosis). Evidence is presented to show the development of morphological abnormalities of the brain with progression of type 1 DM in children. Damage in the formation of white and gray matter, hippocampus, amygdala, the processes of myelination disorders have been described, which can also be the cause of CD development in this contingent of patients. Peculiarities ofclinical manifestations of CD in children and adolescents with type 1 DM depending on the localization of the brain lesion are described. A more pronounced CD was found in cases when DM debuts in early childhood (up to 5 years). Timely diagnosis and correction of CD in children and adolescents with type 1 DM can improve the therapeutic and prophylactic prognosis in this disease.
The neural crest has long attracted the attention of evolutionary biologists and, more recently, clinical specialists, as research in recent decades has significantly expanded the boundaries of knowledge about the involvement of neural crest and neural crest cells in the development of human pathology. The neural crest and neural crest cells are a unique evolutionarily based embryonic structure. Its discovery completely changed the view of the process of embryogenesis. Knowledge of neural crest development sheds light on many of the most «established» questions of developmental biology and evolution. Our article will reflect on the historical stages of the discovery and study of the neural crest and the impact of this discovery on entrenched ideas about germ layer specificity and the theory of germ layers – the reasoning of the neural crest as the fourth germ layer. The aim of this review is to describe the history of the discovery and study of neural crest and neural crest cells based on an analysis of the literature. In writing this article, an analysis of the scientific literature was conducted using the search terms «neural crest», «neural crest cells», «neural crest cell morphology», «germinal layers» and «embryonic development» in the computer databases PubMed, Scopus, Web of Science, and eLibrary. The depth of the analytical search corresponds to the period of the discovery of the neural crest and the first mention of the neural crest as an embryonic morphological structure in the scientific literature. The information presented confirms the high interest of research scientists and clinical specialists in the study of neural crest and neural crest cells. The involvement of neural crest cells in the formation of somatic and musculoskeletal pathologies has received particular attention in recent decades. The literature sources are represented by 169 full-text manuscripts and monographs mainly in English. Conclusions. Neural crest and neural crest cells are unique evolutionary structures. Regularities of formation, reasons which condition migration, differentiation, interaction of neural crest cells with other structures during embryogenesis as well as their potential, which is realized in postnatal period, continue to be the subject of research up to now.
ОБЗОР ЛИТЕРАТУРЫ
The article presents an overview of modern scientific publications on echinococcosis and alveococcosis of the brain, which occur in 1–4 % of cases among all volumetric formations of the central nervous system. Despite the fact that these parasitic diseases are more common in endemic areas of developing countries in Asia, South America, Australia and New Zealand, isolated clinical cases are observed everywhere, including due to population migration, and they must bedifferentiated, first of all, from intracerebral cysts, abscesses, cystic tumors. Clinical manifestations of echinococcosis and alveococcosis of the brain include the development of hypertensive symptoms, focal neurological deficit, convulsive syndrome (with cortical localization of cysts). The article presents the modern possibilities of diagnostic methods (among which the main role is played by neuroimaging methods, such as multislice computed tomography and magnetic resonance imaging using contrast/paramagnet), and surgical and medical treatment of patients with echinococcosis and alveococcosis of the brain. The article also describes two own clinical observations of patients who were hospitalized in the neurosurgical department of the Regional Clinical Hospital (Krasnoyarsk).
PHYSIOLOGY
Knowledge in interrelations between gross anatomy of the left atrial appendage (LAA) and thickness of the walls of LAA and periauricular area enables decreasing operational risks in LAA ostium occluding and «Cox-Maze» surgery for atrial fibrillation. The aim of the study was to identify significant interrelations between the macroscopic characteristics of the LAA (size, shape, number of lobes) and the parameters of the wall thickness of the LAA and its isthmus. Material and methods. The study includes 50 heart specimens of patients died from non-cardiac diseases. We examined 60 anatomical sections from 30 hearts by means Olympus SZX2-ZB10 microscope, and histological slices from 20 hearts. Results. The layers of the LAA wall were thinner than those in the isthmus. The thickness of LAA walls did not show direct correlation with the external dimensions of LAA. We found inverse correlation (Rs = – 0.4, p < 0,05) between the thickness of the myocardium, endocardium and some external sizes of LAA. The wall thickness of «chicken wing», «cauliflower» and «arrowhead» was the same. The wall of single-lobe LAA was thinner than that of two-lobed LAA (p = 0.036). The LAA isthmus wall was thinner (p = 0.03) in hearts with «cauliflower» LAA compared to hearts with LAA resembled a «chicken wing». Differences in wall thickness in LAA of various shapes were due to the degree of subepicardial fatty tissue development. Intracardiac operations should be done with the utmost care in patients with «cauliflower» LAA and single-lobe LAA to avoid damage of the LAA and periauricular area. Conclusions. The research found clinically significant interrelations between the LAA wall thickness and the number of its lobes as well as between the LAA isthmus wall thickness and LAA shape variants.
BIOMEDICINE
Particular attention in the study of comorbid conditions is paid to viral diseases, in particular, those caused by the pandemic influenza virus type A subtype H1N1, as one of the most pathogenic and contagious. Investigation of the effect of this virus in the development of diabetes mellitus will make it possible to more effectively carry out preclinical studies to find the most effective methods of treating a viral infection against the background of a pre-existing somatic pathology. Purpose of the study was to evaluate the pancreatic toxicity effect of exposure to influenza A/H1N1-California virus in the development of streptozotocin diabetes in DBA/2 and BALB/c mice. Material and methods. Groups of mice DBA/2 (n = 36) and BALB/c (n = 58) were formed: infected with influenza A/H1N1-California virus (at different doses); with the introduction of a solution of streptozotocin at a dose of 150 mg / kg; with the combined use of agents. Life expectancy, blood glucose and insulin level, pathomorphological changes in the pancreas were assessed. Results and discussion. The death of animals was observed only in mice of the DBA/2 line: with the introduction of streptozotocin – 12.5 %, with intranasal infection with the virus (at a dose of 5.7 lg TCID50) – 80 %, with combined exposure – 78 %. A comparative study of mice of the DBA/2 and BALB/c lines showed the possibility of using mice of both lines to study the combined effect of influenza A/H1N1 virus and experimental diabetes, taking into account the dose of infection. Infection of BALB/c mice caused the formation of morphological changes only in the exocrine part of the pancreas. In mice of both lines, after the administration of streptozotocin, persistent hyperglycemia was formed, and pathomorphological changes in the pancreas were recorded mainly in the endocrine part. Similar changes in the pancreas, but more severe, involving the exocrine zone, were found during subsequent infection: in mice of the DBA/2 line in the form of a focal disorder of the acinar structure with degeneration of acinocytes and a compensatory regenerative reaction of cells in intact areas; in mice of the BALB/c line in the form of more significant damage to the ductal system than in DBA/2 with the formation of powerful periductal fibrosis and mononuclear infiltrates. Conclusions. A comparative study showed that DBA/2 mice had more pronounced changes in both the exocrine and endocrine apparatus of the pancreas when infected with influenza A/H1N1-California virus and experimental diabetes mellitus.
The use of enzyme preparations is a traditional trend in various fields of medicine. The usage of immobilized enzymes hyaluronidase (IG) and subtilisin (IS) seems to be very promising for the treatment of damage to the ocular surface. The aim of the study was to establish the nature of changes in the ultrastructural organization of human conjunctival epithelium under the influence of immobilized hyaluronidase and subtilisin in vitro. Material and methods. In the experiment, a culture of normal cells of the human conjunctiva Chanqconjunctiva, clone 1–5 C-4, was seeded in 96well plates in the amount of 2 × 104 cells/well, after 24 h the medium was removed, Eagle’s medium MEM and fetal calf serum were added and cells were cultured for another 48 h. 5 experimental groups were formed: group 1 – without drugs (except for the composition of the incubation scheme), groups 2 and 3 – with IS at a concentration of 37 and 150 U/ml, respectively, groups 4 and 5 – with IG at a concentration of 37 and 150 U/ml, respectively. After preparation of cell preparations under a JEM 1400 electron microscope (Japan), ultrathin sections of 70–100 nm were studied at ×1000 magnification. Results. The article presents the results of electron microscopy of a culture of normal cells of the human conjunctiva in 5 experimental groups of cells with a description of changes in cytoarchitectonics under the influence of IG and IS. Conclusions. The introduction of immobilized enzymes into human conjunctival cell culture at a low dose (37 U/ml) affects the organization of cells without cytotoxic effects, while increasing the dose directly correlates with the occurrence of a cytotoxic effect.
Nimesulide (NIM) is a nonsteroid anti-inflammatory drug which acts as a selective cyclooxygenase 2 inhibitor and is widely used for acute pain treatment. In medical practice, a large amount of data has been collected describing the effect of NIM on the body, while a hepatotoxic side effect of the drug has been found. The exact mechanisms of such NIM-induced hepatotoxicity largely remain unknown but likely involve the intermediate reaction of its metabolism. Reduction of the hepatotoxic side effect of NIM is an actual problem for pharmacology. The aim of the present research was to evaluate the hepatotoxicity of the mechanochemically obtained composition of NIM with glycyrrhizic acid disodium salt (Na2GA) compared to pure NIM and a physical mixture of NIM with Na2GA. Material and methods. CD-1 mice were orally administered for 14 days: 1 group – mechanochemical composition NIM/Na2GA (1:10, m/m) at a dose of 1650 mg/kg; 2 group – physical mixture of NIM with Na2GA (1:10, m/m) at a dose of 1650 mg/kg; 3 group – pure NIM at a dose of 600 mg/kg (which pharmacokinetically corresponds to 1650 mg/kg of NIM/Na2GA); 4 group – vehicle (distilled water). The liver damage was assessed using histological studies and enzymatic activity of the alanine aminotransferase and aspartate aminotransferase in blood serum. Results. Histological analysis did not detect any changes in the liver of NIM/Na2GA-treated animals in comparison with a water-treated group. On the opposite, NIM given alone or as a physical mixture with Na2GA induced severe hepatotoxicity in experimental mice. Biochemical analysis of the blood serum revealed that mechanochemical NIM/Na2GA composition significantly reduced activity of the alanine aminotransferase (about 1.5 times) and aspartate aminotransferase (1.3 times) as compared with the pure NIM. Conclusions. The results obtained indicate a high potential for the practical application of the NIM/Na2GA mechanochemical composition.
Quality assurance of transfusion media is a fundamental principle of the functioning of all blood service institutions, allowing guaranteeing the safety of the recipient. An integral part of the procuring process of blood components is their laboratory testing, which results reliability and reproducibility can be proved by carrying out of validation of analytical methods. The aim of the study was to define the rules for planning and carrying out validation tests of methods for quality control of blood components, including verification of their compliance with established acceptance criteria. Material and methods. The analysis of the literature about the safety of blood components and the quality of laboratory tests was carried out with an assessment of the applied significance of the information proved. Results and discussion. As a result of the work done, a unified model for confirming of the accuracy of determining of the safety indicators of transfusion media was created, which contributes to improving of the quality of donor biomaterial and the effectiveness of therapy. Conclusions. The presented validation design is relevant for medical organizations working in the sphere of blood donation and its components.
The use of mesenchymal stem cells (MSCs), which have a pronounced immunomodulatory activity, is a promising direction in the development of biomedical cell preparations (BMCPs). In oncohematology, the use of BMCPs containing MSCs is aimed at supporting hematopoiesis during cotransplantation with hematopoietic stem cells (HSCs) and suppressing immune conflicts during allogeneic unrelated transplantation and severe autoimmune processes. An obligatory stage of registration of BMCPs is confirmation of the identity of the MSC cell line (CL), which includes the establishment of morphological characteristics, evaluation of the expression of specific markers and proteins, and confirmation of the genetic stability of CL during cultivation. Determination of markers of genetic stability is possible using various methods, however, according to the recommendations of the American National Standardization Institute, the standard is the analysis of short tandem repeats (STR analysis). The purpose of the study is to develop an algorithm for determining the authenticity of BMCPs containing MSCs, including STR analysis. Material and methods. Identification of MSC cells in BMCP was performed according to the criteria of the International Society for Cell Therapy. Viable cells were counted in a Goryaev chamber. Immunophenotypic characteristics of MSCs were determined by flow cytometry. The level of production of specific proteins was assessed using enzyme immunoassay. Genetic stability markers were identified by STR analysis. Results and discussion. The methods were tested in triplicate for ten BMCP samples to confirm the reproducibility and reliability of the results. The developed algorithm for determining the authenticity of BMCP has a high accuracy, as it includes the STR analysis technique, which makes it possible to identify 19 polymorphic STR markers located on different alleles. Using the method will allow BMCP manufacturers to go through the procedure of state registration of drugs.
CLINICAL MEDICINE
Taking into account the conflicting literature data and the ambiguity in the interpretation of parameters of diastolic heart function in patients with coronary heart disease, we conducted an analysis of diastolic heart function in patients after myocardial infarction at the outpatient rehabilitation stage. Aim of the study was to investigate the diagnostic information content and the feasibility of diastolic stress testing to assess the functional condition of postinfarction myocardium. Material and methods. 86 patients were examined at the outpatient stage of rehabilitation 6 weeks after myocardial infarction with coronary artery stenting ad hoc. The control group consisted of 10 healthy volunteers. Structural and functional examination of the heart was performed at rest and immediately after exercise using stress echocardiography. Results and discussion. Patients after myocardial infarction have a larger indexed volume of the left atrium (30.71 ± 8.88 vs. 20.49 ± 4.04 ml/m2) and an E/e` ratio (8.45 ± 3.27 vs. 6.46 ± 1.42) in comparison with the control group. 38 (62.3 %) patients with normal left ventricular (LV) ejection fraction (EF) had unimpaired LV diastolic function, 19 (31.1 %) and 2 (3.3 %) patients had type 1 and type 2 diastolic dysfunction, respectively, 2 patients (3,3 %) had an indeterminate result. Patients with reduced LV EF have a significantly lower early diastolic mitral annular velocity (e`). The diastolic stress test revealed a significant post-exercise increase in E/e` in only one patient (from 8.92 to 18.37), who also had an initially reduced EF (32 %). The stress test showed no significant changes in diastolic heart parameters after exercise in patients suffering from heart failure with preserved EF, which may indicate relatively good diastolic reserves of the heart. Conclusions. Myocardial infarction is accompanied by the presence of LV diastolic dysfunction in 53,5 % of the patients at the 6th week of the rehabilitation period. The diastolic stress test is accompanied by a rare occurrence of stress-induced diastolic dysfunction (4 %) in patients with reduced LV EF after myocardial infarction.
The aim of the study was to establish the age and sex patterns of the topography of the ascending and descending colons of children and adolescents according to intravital imaging data. Material and methods. Computed tomograms of the abdomen of 88 children and adolescents without visible abdominal organs pathology were analyzed. The surveyedwere divided into 4 age groups: periods of early, first and second childhood, adolescence. The study was performed on 16-slice computed tomographs with the determination of the distances from the ascending and descending colon to the surface of the body, neighboring organs and anatomical structures of the abdomen, skeletotopia. The data obtained were subjected to variation-statistical processing with the determination of the median, the values of the 25th and 75th percentiles and the significance of differences according to the Mann – Whitney U test. Results and discussion. The article presents the topographic and anatomical characteristics of the ascending and descending colons of children and adolescents and establishes the patterns of change, taking into account the sex and age of the examined. Conclusions. A significant increase in the distance from the ascending colon to the right ureter, jejunum and ileum, and quadratus lumborum was determined. The distance from the body surface to the ascending colon increased with age along all the studied lines. The proximal part of the ascending colon among all those examined was mostly defined from the intervertebral disc LIV–LV to the intervertebral disc LV–SI, and the hepatic flexure of the colon was defined at the level from LI to the intervertebral disc LII–LIII. A significant increase in the distance from the descending colon to the left ureter, pancreas and quadratus lumborum was found. The distance from the body surface to the descending colon increased with age along the anterior median, left middle axillary, and left scapular lines. The splenic flexure of the colon was located at the level from LI to the intervertebral disc LI–LII, and the distal part of the descending colon was located at the level from LIV to the intervertebral disc LIV–LV.
Reports that the risk of developing cardiovascular diseases in obesity is not the same, led to the allocation of metabolically healthy and unhealthy phenotypes (MHP and MUHP), this concept is based on the ability of adipose tissue to produce a number of adipokines, one of which is leptin. Hormones such as thyroid-stimulating hormone (TSH) and prolactin (PRL) are interesting from the point of view of their effect on metabolism. Aim of the study was to investigate the prevalence of MHP and MUHP in young women with different body mass index (BMI) and hormonal status (TSH, PRL, leptin) in different phenotypes. Material and methods. A group of women (n = 655) was selected from a representative sample of the Novosibirsk population aged 25–44 to study clinical and laboratory parameters. The design is a cross – sectional, observational, single – centre study. IDF, 2005 and NCEP ATP III, 2001 criteria were used to evaluate the MHP and MUHP. Results and discussion. The prevalence of MUHP in young women in Novosibirsk was 22.3 %, MHP – 77.7 % according to IDF, 2005; according to NCEP ATP III, 2001 – 13.1 and 86.9 %, respectively. The prevalence of MUHP increased with increasing BMI from 4.0 to 72.0 % according to IDF, 2005 and from 2.3 to 58.0 % according to NCEP ATP III, 2001, respectively. In obese women, MUHP was detected twice as often as MHP – 72 and 28 % according to IDF, 2005, 58 and 42 % according to NCEP ATP III, 2001. TSH and PRL do not provide information about metabolic health in young women. Leptin content is associated with BMI. The threshold value of the leptin level was 18.3 ng/ml with maximum sensitivity and specificity (Se = 53.3 %, Sp = 81.5 %), 14.5 ng/ml with equal sensitivity and specificity (Se = 65.7 %, Sp = 65.7 %). The area under ROC curve (AUC) for diagnosis of MUHP was 0.727 (SE = 0.029, p < 0.0001). Conclusion. The frequency of MHP in young women decreases with increasing BMI. MUHP is 3.5 times less common than MHP according to IDF criteria, 2005. TSH and PRL are not associated with the metabolic phenotype in young women. A leptin level more than 18.3 ng/ml has been identified as one of the markers for the recognition of MUHP in women aged 25–44 years, regardless of BMI.
Aim of the study was to consider a clinical example of diverticular disease of the sigmoid colon, complicated by a tubular intestinal fistula of the anterior abdominal wall and cicatricial stricture of the sigmoid colon. Material and methods. Patient B., 76 years old, was admitted to the proctology department with complaints of the presence of a fistula with purulent discharge in the area of the surgical scar. Preoperative examination with MRI, colonoscopy, fistulography revealed diverticular disease of the sigmoid colon, complicated by a tubular intestinal fistula of the anterior abdominalwall and stricture of the sigmoid colon at the level of the internal opening of the fistula. Results. The operation was performed in the following volume - excision of the fistula, resection of the sigmoid colon bearing the fistula, with endto-end anastomosis in the area without diverticula.
ISSN 2410-2520 (Online)