Human anatomy
Serine proteases, including trypsin, thrombin, plasminogen activators, plasmin and several others, are synthesized in nervous tissue, mainly in the brain, including the cortex, limbic system and cerebellum. This review examines the involvement of serine proteases in neuroplasticity and behavioral regulation. Endogenous serine proteases play an important role in the formation, development and maintenance of the nervous system. Through limited proteolysis, these proteases activate PARs (protease-activated receptors), modify other receptors or their ligands, process neurotrophic factors, degrade intercellular matrix and cell adhesion proteins and initiate complex signal transduction cascades necessary for structural modification of synapses. The involvement of serine proteases in morphological and functional synaptic plasticity may underlie cognitive processes, including learning and memory in animals and humans.
An anthropometric examination and somatotyping of 3280 schoolchildren and students of Krasnoyarsk were carried out during the research this article dedicated to. 1109 females aged 8 to 20 years and 902 males aged 8 to 21 years old were examined. The following parameters were measured: body length, body weight, girth, anterior-posterior and transverse diameters of the chest. The constitution type was calculated using the Rees-Eysenck index. The study found that the average values of most anthropometric indicators are lower in females in all age periods, while the maximum difference in indicators is noted in the youth group. The predominant type of constitution in girls and women is asthenic. Its share was 48,9% during the second childhood, 44,1% during adolescence and 61,5% during young adulthood. The proportion of pyknic somatotype decreases with age from 21,0% to 10,6%. In boys and men, the predominant type of constitution is normosthenic, defined in 46.3% of boys during the second childhood, in 50,5% of adolescents and 53,9% of young men. The pyknic type ranges from 20,4% to 26,7% in different age periods. A decrease in the asthenic type of constitution with age from 33,2% to 21,9% was determined.
Doxorubicin is actively used in scientific practice not only as a chemotherapeutic drug, but also as a senescence inducer due to its mechanism of action, namely, the blocking of mitosis, the development of mitochondrial dysfunction and DNA intercalation, which is most pronounced in labile cell populations. The senescent phenotype is currently considered as one of the possible options for the induction of prooncogenes, failure of repair processes and local inflammatory response. The combined use of senolytics together with chemotherapy drugs has been used for a long time (quercetin and dasatinib), however, the combination of peptide-based senolytics (FOXO4-DRI) with doxorubicin seems to be one of the most promising. This article discusses the combined use of FOXO4-DRI and doxorubicin in female and male mice in the early stages. As a result, microscopic examination showed a moderate protective effect of the senolytic peptide on the liver cell population, a decrease in the degree of leukocyte infiltration, and a decrease in the degree of fatty infiltration. There was a significant difference in responses between animals of different sexes.
Pathophysiology
The review shows the statistics about the epilepsy morbidity in different countries, including Russia and its individual regions. We discuss various mechanisms of development of epileptic hyperexcitability of brain neurons. We summarize the knowledge about the role of ion imbalance, transmitters, neurochemical disorders in the epileptic activity development, both acquired and hereditary, including the significance of molecular genetic alterations, namely mutations and epigenetic mechanisms that together cause pathological changes in the membrane potential of brain neurons. The article highlights the causes and mechanisms of development of membrane channelopathy and transmembrane ion transport disorders, which underlie changes in the electrophysiological properties of neurons. The article provides information from Russian and foreign literature about the significance of immunological and cytokine shifts in the pathogenesis of epileptic hyperexcitability of neurons in different parts of the brain.
A total of 70 children were studied, including 35 with type 1 diabetes mellitus (study group) and 35 conditionally healthy children (control group). Patients with type 1 diabetes mellitus were studied at two stages: upon their urgent admission to the hospital with diabetic ketoacidosis (stage one, acute period) and two months later, during planned hospitalization (stage two, recovery period). Children with type 1 diabetes mellitus were found to have elevated levels of autoantibodies against the melatonin receptor (MRA1), with the maximum concentration during the acute period reaching 5.17±1.02 U/mL and subsequent gradual decrease to a level of 2.3±0.31 U/mL two months later. Positive correlation was found between the level of anti-MRA1 AAT and chronic disease course (duration of disease, number of relapses in the patient’s history). An explanation is provided for chronobiological mechanisms involved in the pathophysiology of pediatric type 1 diabetes mellitus.
The article deals with the issues of childhood oncopathology. Based on the literature data, the structure of oncological diseases in children in the Russian Federation and in the Novgorod region has been analyzed. It is shown that due to the rarity of oncological diseases in childhood, their detectability in outpatients in clinics requires active study with pediatricians by increasing staff awareness of this group of diseases and developing doctors’ oncological alertness skill in routine work. The article highlights the mechanisms of pathogenesis of a rare malignant embryonic neoplasm of the kidney — nephroblastoma (Wilms tumor), describes the clinical symptoms. The authors' own observation of an infant with a diagnosis of Wilms tumor is given. Conclusions were obtained about the course of the disease, the timing of the manifestation of the clinical picture. The observation demonstrates the relevance of timely screening ultrasound examination of the abdominal cavity and kidneys for children of the first year of life, the need to increase the level of knowledge in pediatric oncology of pediatricians of outpatient clinics, ultrasound diagnostics specialists, since timely diagnosis and early treatment significantly increase the likelihood of achieving remission of malignant diseases in children.
The work is devoted to the analysis of indicators of the reactivity of the ghrelin system in the model of psychogenic stress. In recent years, it has been shown that the significance of the ghrelin system of the brain is not limited to the regulation of energy balance and eating behavior. It has been established that short-term stress experience is expressed by erosive inflammation of the mucous membrane, the death of many mucous cells, as well as an increase in the degree of mucoid cell differentiation of exocrinocytes. Along with other peptide regulatory systems, it plays an important role in the mechanisms of stress, reinforcement and addiction. Therefore, it is advisable to consider the elements of this system, first of all, as molecular targets of pharmacological action in order to correct the states of addiction and post-stress disorders. Using histological, immunohistochemical and morphometric methods, reactive changes in ghrelin-producing endocrinocytes of the stomach and hypothalamus, as well as elements of the inner part of the gastric mucosa, were established in the model of psychogenic stress and after replacement therapy. The short-term experience of psychogenic stress in the experimental model is expressed by persistent degenerative changes in GPEC (ghrelin-producing endocrine cells), erosive inflammation of the gastric mucosa, the death of many mucous cells, and an increase in mucus production in viable epithelial cells. Neuropeptide regulatory systems (ghrelin, kisspeptins, orexins, dynorphin, and others) are increasingly involved in physiological and pharmacological experiments on modeling the development of an organism at different levels of its organization and a number of major functional disorders (memory, satiety, stress, addictions). The adaptive changes observed in the gastric mucosa after stress and ghrelin replacement therapy may be due to the modulating effect of ghrelin on corticoliberin-producing neurons. Meanwhile, information about their functional morphology is just beginning to accumulate.
The severity of the condition in patients with the main diagnosis "new coronavirus infection caused by COVID-19 virus, complicated by the development of community-acquired bilateral multisegmental viral pneumonia of moderate severity" was assessed by laboratory parameters in the blood serum (glucose, creactive protein, total protein, cholesterol, creatinine). Patients diagnosed with comorbidities, such as type 2 diabetes mellitus and cardiovascular diseases, in addition to COVID-19, and the control group of patients without comorbidity were included in the study. The presence of diagnosed obesity in the patients was also assessed. Changes in blood serum parameters from the moment of admission and at the time of discharge of the patients, depending on the concomitant pathology, were measured. The most pronounced changes in blood biomarkers were observed in the patients with a combination of concomitant cardiovascular diseases and concomitant diabetes mellitus. When comparing the two groups, with only cardiovascular comorbidity and only concomitant diabetes mellitus, a greater effect of concomitant cardiovascular diseases on blood biomarkers in the patients was noted. Separately it is worth noting obesity as a factor affecting the pathological increase in blood glucose levels in the patients after even a short-term COVID-19 treatment.
Occupational diseases and harmful production factors contribute to a significant disability of the working population. This article discusses some morphological aspects of changes in the lungs of experimental animals after the introduction of coal suspension into the respiratory tract. Specific and non-specific responses of lung tissue to the damage were determined. The object of the study was white outbred rats, formed according to the principle of pairs of analogues, with the separation of the experimental and control groups. On the 10th day of the experiment, the animals were withdrawn from the experiment, with a preliminary multislice computed tomography and subsequent microscopic assessment of the organization of the lung parenchyma. As a result, computed tomography revealed a pronounced reaction with the formation of emphysema in the subpleural parts of the lungs. Microscopic examination revealed non-specific types of responses to the introduction of coal dust with the formation of leukocyte infiltration in various parts of the lungs, accumulation of mucus and coal dust in the respiratory bronchioles.
Pharmacology, clinical pharmacology
Currently, the problem of psoriatic arthritis is very relevant and attracts the attention of researchers from the standpoint of studying the factors associated with all aspects of this disease, including the effectiveness of the therapy. The present study was aimed at studying the possibility of the influence of sex on the development of secondary failure of genetically engineered biological drugs in bio-naive patients with psoriatic arthritis. According to the results obtained, among patients receiving genetically engineered biological therapy, the period of development of secondary failure of the first-line genetically engineered biological drug was higher in women. The revealed pattern differs from the results obtained when comparing the survival of genetically engineered biological therapy in general in men and women with psoriatic arthritis but correlates with data on sex differences in the course and manifestations of the disease. Thus, the results of the study suggest the influence of sex on the development of secondary failure of genetically engineered biological drugs in patients with psoriatic arthritis, which necessitates further research in this direction with greater selectivity.
This literature review presents current data on the role of the vascular endothelial growth factor (VEGF) in physiology and pathology and its application in ophthalmology. The main physiological properties of the VEGF family factors and the role of their receptors in the development and regulation of angiogenesis are described. Clarification of the mechanisms of vascular growth in physiological conditions is necessary to understand the processes of formation of new vessels, since their violation underlies the development of many diseases, including in ophthalmology. Medicines used in ophthalmology that inhibit VEGF-mediated angiogenesis are presented in this review. A number of reports describe signs of retinal damage during anti-VEGF therapy. It is currently unclear whether retinal toxicity from VEGF-A neutralization arises from impaired direct VEGF-A-mediated cytoprotection or from an indirect effect such as impaired VEGF-A-mediated vascular perfusion. Therefore, the further study of the physiological role of the vascular endothelial growth factor will allow the development of new medicines for the treatment and prevention of eye diseases.
Regenerative medicine. Sports medicine
The article describes the components of the respiratory rehabilitation program for patients who
have undergone COVID-19. Domains from the ICF categories were selected, formed into a short ICF table
with the addition of an ICF determinant for the convenience of assessing the ongoing rehabilitation of
patients who have undergone the new coronavirus infection. The effectiveness of rehabilitation in both
groups was assessed on the basis of GOST R 57960–2017 "Evaluation of Rehabilitation Services
Outcomes".
Clinical laboratory diagnostics
The results of treatment of 118 patients with obstructive jaundice of non-tumor etiology have been analyzed. All patients were divided into control and main groups according to the volume of preoperative preparation and stages of surgical treatment. The control group consisted of 30 patients who were operated after a short-term standard preparation including cholecystectomy and biliary decompression. The main group consisted of 88 patients who underwent two- or three-stage surgical interventions on the biliary tract and lymphatic system, which included external drainage of the thoracic duct, endoscopic papillosphincterotomy and lymphovenous anastomosis. The mortality rate in the control group was 23.2%, of which 8% of patients with jaundice duration up to 10 days, 45% — with jaundice duration up to 14 days. In the main group, the overall mortality was 5.5%, which is 4.2 times lower than in the control group. Of those with a duration of cholestasis up to 10 days, there was no mortality, in patients with a duration of biliary occlusion up to 14 days, it was 7% and in patients with a duration of up to 3–6 weeks — 15%. According to the indications, lymphovenous anastomosis was performed in 39 patients; there was no mortality cases among these patients. During the study, it was confirmed that lymphatic drainage operations in combination with endoscopic biliary decompression help to reduce porto-lymphatic pressure, sanitize the biliary tract, reduce endogenous intoxication and improve treatment outcomes.
The article presents a clinical case of B12-deficiency anemia in combination with active cytomegalovirus infection in a one-year-old child. This type of anemia is extremely rare in childhood, under certain circumstances, including the enthusiasm for restrictive diets among young patients’ mothers. In the described case, severe megaloblastic macrocytic anemia was combined with generalized cytomegalovirus infection, which aggravated the course and prognosis of the disease. These pathologies led to damage of the central nervous system with a tempo neurological deficit, as well as the development of protein-energy insufficiency. Complex therapy included hemotransfusion of erythrocyte mass, injections of anticytomegalovirus immunoglobulin and cyanocobalamin. The general condition of the child improved, recovery of previously lost skills and significant positive laboratory dynamics were noted after the therapy.
In many countries, there has recently been an increase in the frequency of cesarean section (C-section). In developed countries, the C-section rate has reached 30%; in Russia, it varies from 3 to 47,4%. Recent studies have also shown an increase in postoperative complications associated with C-section. This research aims to assess the disclosure of the problem of suture (scar) failure after C-section and to investigate the role of common clinical risk factors and laboratory markers in the development of suture failure associated with C-sections. This study expands our understanding of the actual diagnostics of this pathology. The authors introduce a variant of solving the problem of reducing the risk of postoperative complications in women after C-sections in the form of developing a computer program for predicting the development of this pathology.