ORIGINAL RESEARCH
Introduction. The number of overweight and obese people worldwide is steadily increasing. Metabolic disorders caused by excessive accumulation of body fat signifi cantly aff ect the development and course of functional changes in the body, in particular arterial hypertension (AH).
Aim. Determination and evaluation of the levels of carbohydrates, lipids and sex hormones in women of reproductive age with АН and associated metabolic syndrome (MS). Materials and methods. The study included 2 groups of women of reproductive age: the main group consisted of 30 patients with AH grade 1 and MS who were treated at the Aktobe Medical Center (Aktobe, Kazakhstan); control one consisted of 20 apparently healthy women who were examined at the Family Medicine Clinic of the West Kazakhstan Marat Ospanov Medical University. The groups were comparable in age (35–49 years). Along with the blood pressure and body measurements, some biochemical parameters were determined in all patients, and the heart performance indicators were also assessed (using echocardiography).
Results. Changes of intracardiac hemodynamics in patients of the main group were revealed: an increase in left ventricle end-diastolic and end-systolic volume, as well as stroke volume. A biochemical analysis revealed an increase in glucose and triglyceride values in the main group, as well as an increase in the level of low-density lipoproteins and a decrease in the level of high-density lipoproteins in the main group compared to the control one.
Conclusion. The development and progression of MS has a signifi cant impact on the overall health status of patients and increases the risk of development and progression of АН.
Aim. Evaluation of the eff ectiveness of the outpatient follow-up of patients during the fi rst year after myocardial infarc- tion (MI) and compliance of care of these patients with the current guidelines for diagnosis and treatment.
Materials and methods. Data from outpatient medical records of 96 patients (64 men and 32 women, mean age 61.6 years [43.1; 76.5]) who were followed up in 2021 in various outpatient clinics of Novosibirsk during the year after MI were analyzed.
Results . As a result of the analysis of outpatient medical records, insuffi cient detection of such cardiovascular risk factors as arterial hypertension (AH) (42 (43.8%)) and statin use (14 (14.6%)), and insuffi cient compliance with guidelines for outpatient follow-up of patients after the event (frequency of administering the angiotensin-converting enzyme inhibi- tors/angiotensin II receptor blockers was 32 (33.3%), beta-blockers – 84 (87.5%), dual antithrombotic therapy – 59 (61.5%), statins – 88 (91.7%) with an average level of low-density lipoprotein cholesterol – 2.6 [2.4; 4.7] mmol/l) were revealed.
Conclusion. Outpatient management of patients – residents of Novosibirsk within 12 months after MI gives grounds to speak about the insuffi cient frequency of detection and correction of the main cardiovascular risk factors in the period preceding MI and insuffi cient compliance with guidelines for outpatient follow-up of patients after the event.
Introduction . A novel coronavirus infection caused by the SARS-CoV-2 virus is a highly contagious disease with a signifi cant risk of complications up to mortality. The development of anti-SARS-CoV-2 drugs began almost immediately after the identifi cation of the virus, while two promising pharmacological targets were identifi ed: the main and papain-like proteases.
Aim . Evaluation of the eff ect of new derivatives of 6,7-dimethoxyquinazoline-4(3H)-one with amino acid residues and dipeptide fragments on the activity of SARS-CoV-2 proteases in vitro.
Materials and methods . The studied substances were obtained from commercially available 2-amino- 4,5-dimethoxybenzoic acid which were cyclized into 2-alkyl-6,7-dimethoxy-3,1-benzoxazine-4-ones, followed by reaction with amino acids and dipeptides. The changes in the activity of viral proteases were evaluated with spectrophotometry using the appropriate substrates. During the study, the half maximal inhibitory concentration (IC50) was calculated.
Results . As a result, it was found that the obtained compounds exhibit pronounced inhibitory activity with respect to both the main and papain-like protease of SARS-CoV-2 with an IC50 range of 0.012–0.100 and 0.013-0.100 μM/ml, respectively. The most pronounced eff ect was shown for the 3h compound with a fragment of the glycyl-tryptophan dipeptide with the isopropyl radical, which reduced the activity of the main protease (IC50 0.012 ± 0.005 μM/ml) and the papainlike protease (IC50 0.013 ± 0.009 μM/ml).
Conclusion . Compound 3h containing the isopropyl radical and the glycyl-tryptophan dipeptide may become a promising object for further study and development of a new antiviral agent based on it.
Introduction . The high incidence of arterial hypertension (AH) in the population, its close association with menopause and disorders of carbohydrate metabolism with an emphasis on the predictive role of fasting glycemia (FG) for type 2 diabetes mellitus draws attention to the phenotype of the formation of metabolic syndrome (MS) in perimenopause depending on the presence of hypertension without dysglycemia.
Aim of the research . To evaluate the associations between blood pressure (BP) levels and FG during the formation of insulin resistant menopausal MS in a cohort of normoglycemic women aged 35–59 years with AH and normotensive.
Materials and methods . In the perimenopausal cohort of women aged 35–59 years without dysglycemia (n = 88), 58 women had hypertension, 30 were normotensive. The following were determined: body mass index (BMI), waist circumference (WC), levels of BP, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), insulin, folliclestimulating hormone (FSH) and estradiol, FG, TyG and HOMA2 family (HOMA2-IR and HOMA2-%B) indices. Using SPSS (version 17), we estimated the median (25; 75%); intergroup diff erences according to the Mann-Whitney test; then, the correlation analyses were carried out: according to Spearman (R) and partial (Rpc) to level the infl uence of age.
Results . Signifi cant associations of systolic BP (SBP) and FG levels, direct and mediated through lipid (TG and HDL-C) and anthropometric (WC) parameters of MS, were revealed with most of the correlations being only partially agedependent. Among these parameters, the mediators of insulin resistance, the associations of SBP and FG with WC are the most pronounced; it is WC that stably correlates with insulin resistance indices, more specifi cally with TyG. The correlations of TG levels with HDL-C (R = –0.564; p < 0.001) are also relevant when the infl uence of age is leveled (Rpc = –0.477; p < 0.001); with them, as well as with the levels of insulin and the duration of postmenopause, FG correlates. BP levels, especially systolic, form correlations with insulin resistance indices, more stable with non-insulin TyG index, in contrast to age-dependent relationships with HOMA2-IR.
Conclusion . The extensiveness of the revealed correlations between BP and FG levels with markers and factors for the formation of menopausal MS, including the relation of BP with HOMA2-IR indices and especially TyG, refl ects its insulin resistant pathogenetic basis. Along with this, signifi cant stable correlations of the duration of postmenopause with FG refl ect a high risk of progression to dysglycemia in the analyzed phenotype of metabolic syndrome and allow us to consider menopause as a unique factor contributing to the rapid clustering of MS in women, determining the interest in clarifying its formation trajectories.
I n t r o d u c t i o n . Low population density, complexity of drug delivery, a low level of solvency of rural population, the insuffi ciently developed infrastructure of pharmaceutical care, shortage of pharmaceutical specialists in municipal districts make remote territories unattractive for the development of retail trade of medicines, whereas the inconsistency of state programs for social and economic development of rural areas, the timing of their implementation, diff erent departmental orientation, insuffi cient funding do not allow achieving the targets, which requires an in-depth study of the problems and determining the directions for optimizing retail trade of medicines. A i m . The study of modern problems of retail trade of medicines via separate divisions of medical facilities in the Novosibirsk region (NR).
M a t e r i a l s a n d m e t h o d s . The sources of information were the main health indicators of the NR for 2022, departmental materials of the Ministry of Health of the NR, questionnaires of primary care workers, the register of licenses for pharmaceutical activities in the NR, fi nancial reports of the central district hospitals of the NR for 2022 for 30 municipal districts of the region. According to specially designed questionnaires, 95% of the total number of primary care workers involved in the retailing of medicines via separate divisions of the NR medical organizations (917) were interviewed.
R e s u l t s . In one third (9) of the municipal districts of the NR, the population served by one pharmacy organization is 3057 people, which is characterized as very high and corresponds to low geographic availability of pharmaceutical care. The average number of rural population served by one pharmacy organization in municipal districts in 2022 was 2138 people. According to the number of rural residents per one medical and obstetric station (MOS), the fi rst, second and third groups of municipal districts are the most numerous and available (a total of 22) in which there are from 278 to 531 residents per one MOS, which is 73.33%, and in the rest 8 (26.66%) municipal districts, the average number of rural residents ranges from 718 to 1051, thus exceeding the indicator of the 1st group by 3.78 times. The most cost-eff ective are the drugs included in the fi rst priority group (398 trade names (TN)) which has high indicators in terms of the amount of drugs sold and the number of packages dispensed, but the proportion of drugs of this group is small – 10.75%. The second priority group included 687 TN. The group has average indicators, it accounts for 18.55%. The third priority group consists of drugs with low indicators in terms of the amount of drugs sold and number of packages dispensed (2618 TN; the group’s proportion is 70.70%). The survey of primary care workers showed that only 20.7% of respondents are satisfi ed with the level of knowledge and skills they have. Primary care workers of MOS experience the greatest diffi culties in the order of prescribing medication, accounting and storage of drugs, medical devices and other goods of pharmacy range (57.8%).
C o n c l u s i o n . As a result of the study, 6 groups of municipal districts were identifi ed according to the geographic availability of retailing entities for the subsequent formation of individual development trajectories. The analysis of the realized range of drug allowed us to develop proposals for its optimization for retail trade via MOS. The results of the survey of primary care workers require the development of additional training programs for the retail trade of medicines, making reasonable management decisions to optimize retail trade.
I n t r o d u c t i o n . The pandemic of a novel coronavirus infection (COVID-19) has limited the work of planned medical preventive programs and, together with the consequences of the illness, the lockdown has had a negative impact on the psychosomatic status of the population.
Ai m . Analysis of the dynamics of the adolescent health in the Novosibirsk region during the COVID-19 pandemic which determine the immediate reserve of society.
M a t e r i a l s a n d m e t h o d s . The data on the incidence and disability of adolescents aged 15–17 years in the Novosibirsk region, health indicators of young men based on the results of medical examinations at the Regional Conscription Center during the COVID-19 pandemic (2020–2022) were analyzed. Process trends were recorded by graphical analysis of diagrams, trend modeling, calculation of growth rates and their ranking. R e s u l t s . By the end of 2022, similar trends in the incidence and disability in the form of a signifi cant positive growth rate were found for mental and behavioral disorders, diseases of the nervous system. In the health condition of young men of conscription age, the most negative dynamics was revealed for mental and behavioral disorders, diseases of the respiratory system, endocrine, nutritional and metabolic diseases. The latter were often overlooked during preventive examinations and were fi rst diagnosed at the Conscription Center; their underdiagnosis was facilitated by the workload of the outpatient pediatric setting that worsened during the pandemic.
C o n c l u s i o n . The alarming trends in the health of adolescents in the Novosibirsk region during the pandemic indicate the need to introduce interdisciplinary algorithms for early diagnosis of the consequences of the disease and lockdown into the healthcare system, including both medical and sociopedagogical aspects.
I n t r o d u c t i o n . Hypoproductive thrombocytopenias caused by insuffi cient platelet formation in the bone marrow are usually a manifestation of the underlying process characterized by inhibition of thrombocytopoiesis. They accompany aplastic anemia, acute leukemia, primary myelofi brosis, myelodysplastic syndrome, may be the result of tumor metastasis to the bone marrow, with the substitution of the megakaryocyte lineage, as well as a complication of radiation therapy and chemotherapy.
A i m . To analyze the features of the provision of transfusion support to patients with hypoproductive thrombocytopenia due to oncological or hematological diseases in the day hospital at the Novosibirsk Clinical Blood Center (NCBC).
M a t e r i a l s a n d m e t h o d s . The study included 222 patients of the NCBC day hospital who underwent replacement therapy with platelet concentrate to correct thrombocytopenia and hemorrhagic syndrome for the period 2017–2022.
R e s u l t s . Correction of thrombocytopenia due to malignant neoplasms (solid tumors) was performed in 69 patients and due to hematological diseases – in 153 patients. The average number of doses of platelet concentrate was 3.7 ± 2.4 for patients with solid tumors; the clinical effi cacy of replacement therapy was achieved in this group of patients in all cases. For patients with hematologic-related thrombocytopenia, the average number of doses of platelet concentrate was 3.2 ± 1.3; the clinical effi cacy in this group of patients was achieved in 131 cases out of 153.
C o n c l u s i o n . Replacement therapy with blood components in transfusion-dependent and comorbid patients in a day hospital allows in most cases (85.6%) to carry out eff ective clinical correction of thrombocytopenia and achieve complete reverse of manifestations of hemorrhagic syndrome (100% of cases).
I n t r o d u c t i o n . The expression of miR-143 and miR-145 oncosuppressive microRNAs is observed in all types of normal tissues studied and, according to numerous studies, it is lost in malignant neoplasms. A decrease in the expression of these microRNAs in diff use large B-cell lymphoma (DLBCL) is described, the mechanisms of which require additional study. A i m . To evaluate the methylation of MIR-143 and MIR-145 genes in the lymph node tissue of patients with DLBCL and lymph nodes of patients with reactive follicular hyperplasia.
M a t e r i a l s a n d m e t h o d s . The study included biopsies of 14 formalin-fi xed and paraffi nized tumor lymph nodes of patients with DLBCL and 11 lymph nodes of patients with reactive lymphadenopathy. The methylation status of the MIR-145 gene in samples was determined by the method of methyl-specifi c polymerase chain reaction. Direct bisulfi te sequencing based on the Sanger method was used to quantify the methylation of the MIR-143 gene.
R e s u l t s . It was found that all the studied samples, both reactive and tumor, had methylation of the MIR-145 gene. A similar level of methylation of CpG dinucleotides of the MIR-143 gene was registered in all samples of reactive lymph node tissue, whereas tumor samples showed greater heterogeneity. In the samples of DLBCL, namely a non-germinal B cell phenotype, the average level of methylation of the studied fragment of the MIR-143 gene sequence was signifi cantly lower, than in the samples of reactive lymph nodes (p = 0.026).
C o n c l u s i o n . The methylation of MIR-143 and MIR-145 genes detected in the lymph nodes of patients with DLBCL is not tumor-specifi c. The complex cellular composition of the analyzed samples, as well as the diff erent density of microvessels, may explain the diff erences in the level of MIR-143 methylation in the tissue of reactive and tumor lymph nodes.
I n t r o d u c t i o n . The search for the relationships between clinical features of patients with uterine fi broids (uterine myoma, leiomyoma) and the characteristics of their myomatous nodules is relevant for identifying prognostic markers.
A i m . In patients of reproductive age with uterine fi broids, to identify the presence of correlations between clinical laboratory parameters and markers of infl ammation and fi brosis in the surgical specimens.
M a t e r i a l s a n d m e t h o d s . Myomectomy was performed in 226 female patients with myomatous no dules. Examination of patients included clinical investigations (ultrasound, magnetic resonance imaging), extragenital abnormalities were assessed. Samples of the dominant myomatous nodules and myometrium were examined using enzyme-linked immunosorbent assay (ELISA) for the content of baseline and stimulated by polyclonal activators (PA) vascular endothelial growth factor (VEGF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the incubation medium. The expression of progesterone receptors (PgR) and VEGF using immunohistochemistry (IHC) was assessed.
R e s u l t s . The combination of uterine fi broids with endometriosis in reproductive-aged women infl uenced a number of histological and molecular characteristics of the dominant myomatous nodule: positively – on the grade of fi brosis (p < 0.0001), negatively – on the PA-induced production of GM-CSF and VEGF (p = 0.0054 and p = 0.0016, respectively). Patients with adenomyosis had more myomatous nodules (p = 0.0192) compared with patients without any form of endometriosis, while the largest nodule diameter and the degree of fi brosis were in women without adenomyosis (p = 0.0397 and p = 0.0344, respectively). PA-induced VEGF production in the nodule is greater in adenomyosis (p = 0.0326), while PgR expression in the perifocal myometrium is less (p = 0.045). In patients with uterine myoma, the body mass index had a weak positive correlation with VEGF expression in the perifocal myometrium. The number of myomatous nodules had weak positive correlation with the stimulation index of PA (SIPA) which refl ects their infl uence of the VEGF production in the dominant nodule in vitro. The degree of fi brosis of the dominant nodule was characterized by moderately positive correlation with the expression of VEGF in the perifocal myometrium according to IHC.
C o n c l u s i o n . The results of the study refl ect the systemic nature of myomatous transformation with multifocal myometrium tumor growth and the potential for the formation of new myomatous nodules, especially in women with elevated body mass index.
CLINICAL CASE
Systemic lupus erythematosus (SLE) occurs in diff erent age groups, but the risk group is people aged 15 to 40, most often female adolescents and young women. In clinical practice, the issue of timely verifi cation of the diagnosis of SLE remains relevant. This clinical case illustrates the onset of acute systemic lupus erythematosus in an adolescent, with rapid involvement of vital organs (kidneys, lungs) in the pathological process. At the initial stage, various diagnoses were discussed; however, a comprehensive examination of the patient was carried out only when the patient was admitted to a hospital. The diagnosis of SLE was confi rmed on the basis of classifying criteria: clinical investigation data.
REVIEW
Hereditary cerebellar ataxias (HCA) is a heterogeneous group of genetic neurological neurodegenerative diseases with a steadily progressive course. Ataxia is manifested by disturbed equilibrium, speech. Diseases of this group, as a differrule, lead to disability of the patient. Advances in the field of molecular genetic research have made it possible to determine the form of HCA in accordance with the type of inheritance, and on this basis a classification of HCA has been formed. Monogenic (autosomal dominant, autosomal recessive, X-linked) and non-traditional types of inheritance of cerebellar ataxias (mitochondrial, expansion of trinucleotide repeats) are distinguished, sporadic forms with an unidentified or unknown type of transmission are also distinguished. Thus, HCA are classified into autosomal dominant spinocerebellar ataxias (SCA), they include 48 forms, some of which are polyglutamine SCA, and autosomal recessive, about 100 nosological entities. In addition, episodic cerebellar ataxia is also classified as an autosomal dominant ataxia. Among autosomal dominant ataxias, SCA3 or Machado-Joseph disease is the most common, followed by SCA2 and SCA6. However, in Russia, the prevalence is different. Among autosomal recessive ataxias, the most common is Friedreich’s ataxia, which also belongs to polyglutamine diseases. It should be taken into account that different methodological approaches lead to great heterogeneity and scattering of results in determining the prevalence of one or another form of hereditary ataxia both within the country and among the countries. The review presents current data on the prevalence of various forms of HCA in different regions of the world and populations. However, there is still a great deal of uncertainty regarding the overall prevalence of certain hereditary forms of cerebellar ataxia.