Vol 105, No 4 (2024)

BACKGROUND: There is an opinion that the new coronavirus infection COVID-19 can initiate the development of a local inflammatory reaction in the testicles, which leads to damage to spermatogenic epithelial cells and a decrease in the fertility of patients in the long term.

AIM: Morphofunctional assessment of immunocompetent cells in the testicles of patients with COVID-19 depending on age.

MATERIAL AND METHODS: Based on anamnestic, clinical and morphological data, groups of patients were formed, each of which included subgroups according to the age periodization of the World Health Organization: the first group of patients who died as a result of COVID-19 (n=109; average age 58±2.8 years) — young subgroup (n=19, age 18–44 years), middle-aged subgroup (n=37, age 45–59 years), elderly subgroup (n=53, age 60–74 years); second group (n=30, average age 49±2.3 years; autopsy material from the testicles of patients who died from causes unrelated to COVID-19, obtained outside the pandemic) — a subgroup of young people (n=10, age 18–44 years), middle-aged subgroup (n=10, age 45–59 years), elderly subgroup (n=10, age 60–74 years). Histological and immunohistochemical studies were carried out using primary antibodies to CD3, CD4, CD68, CD163, CD138 and statistical methods: Kolmogorov–Smirnov test, Student's t-test, Mann–Whitney U test and Fisher test.

RESULTS: All testicular samples from patients with COVID-19 revealed signs of viral orchitis and a significant decrease in the spermatogenesis index (in young people — 5.9±0.2% with p=0.02; in middle age — 5.1±0.2% with p=0.008; in the elderly — 3.6±0.1% at p=0.006) compared to the control group (6.8±0.3%), and in immunohistochemical studies — an increase in the number of T-lymphocytes (CD3⁺, CD4⁺), macrophages (CD68⁺, CD163⁺) and plasma cells (CD138⁺) in interstitial tissue. In addition, a significant decrease in the spermatogenesis index (3.6±0.1% in the elderly versus 5.9±0.2% in the young, p=0.007) and a decrease in the number of T-lymphocytes (CD3⁺, CD4⁺) and macrophages (CD68⁺, CD163⁺) was found in older versus younger patients with COVID-19.

CONCLUSION: In patients with COVID-19, an increase in the number of immunocompetent cells (CD3⁺, CD4⁺, CD68⁺, CD138⁺, CD163⁺) in the interstitial tissue of the testicles was found, especially pronounced in the elderly group.

BACKGROUND: A key role in the pathogenesis of colon cancer is assigned to inducers of neoangiogenesis — vascular endothelial and epidermal growth factors, the effects of which can probably be modulated by galectins-1 and -3.

AIM: To study the relationship between the content of galectins-1 and -3, vascular endothelial and epidermal growth factors with the number of circulating endothelial cells in the blood of patients with colon cancer, depending on the degree of tumor differentiation and its spread.

MATERIAL AND METHODS: Patients (n=20) with a verified diagnosis of colon cancer (International Classification of Diseases code C18–C20) were examined; the comparison group included healthy volunteers (n=10), matched by gender and age. The study material was peripheral blood. The content of galectin-1, galectin-3, vascular endothelial and epidermal growth factors was assessed by enzyme immunoassay, and counting of desquamated endothelial cells was assessed by flow cytometry. Statistical processing was performed in the Jamovi 2.3.21 software package for Windows. Differences between samples were assessed by calculating the Mann–Whitney U test. Relationships were established by calculating the Spearman correlation coefficient (ρ). The results were considered reliable at the level of statistical significance p <0.05.

RESULTS: In patients with colorectal cancer, the level of vascular endothelial factor was higher than in healthy donors by 18%, the level of galectin-1 was 2.6 times higher, galectin-3 was 1.6 times higher compared to healthy donors, the level of epidermal growth factor did not differ significantly. The content of galectins-1 and -3 was closely interrelated (ρ=0.843, p <0.01), with the content of vascular endothelial growth factor in the blood plasma (ρ=0.311, p=0.032 — galectin-1; ρ=0.310, p <0.033 — galectin-3, respectively). The number of desquamated endothelial cells in the blood of patients with colorectal cancer was 8 times higher than in healthy people, and directly correlated with the content of vascular endothelial growth factor (ρ=0.307, p <0.05), galectin-1 (ρ=0.650, p <0.01) and galectin-3 (ρ=0.622, p <0.01).

CONCLUSION: An increase in the content of galectins-1 and -3 in the blood plasma of patients with colon cancer positively correlates with the expression of vascular endothelial growth factor, and does not depend on the stage of the disease and the degree of tumor differentiation.

BACKGROUND: The combination of chronic heart failure and chronic obstructive pulmonary disease contributes to the formation of the phenotype and survival of patients.

AIM: To study the 5-year prognosis and develop a prognostic model of adverse events in patients with chronic heart failure of ischemic origin in comorbidity with chronic obstructive pulmonary disease.

MATERIAL AND METHODS: Clinical signs of patients with chronic heart failure of ischemic origin (n=517), including those in combination with chronic obstructive pulmonary disease (n=118), and outcomes over 5 years according to end points: death from all causes, cardiovascular death, composite endpoint — all fatal and non-fatal cardiovascular events, were studied. Quantitative variables were presented as mean and standard deviation or median and interquartile range; categorical — in the form of absolute value and percentage. Quantitative intergroup differences were assessed using the Mann–Whitney test, and categorical differences were assessed using the Pearson χ² test. Time to event was analyzed using the Kaplan–Meier method; hazard ratio — by Cox regression. Models were developed using binary logistic regression. Statistical processing was carried out in the Jamovi, R 4.3.1 programs.

RESULTS: The clinical portrait of a patient with chronic heart failure of ischemic origin in the presence of chronic obstructive pulmonary disease was characterized by a predominance of men in older age groups, a high frequency of smoking, a worse quality of life, determined by the Minnesota Questionnaire, and a high level of high-sensitivity C-reactive protein, α₁- and α₂-globulins. Patients with heart failure in the presence of chronic obstructive pulmonary disease had higher overall and cardiovascular mortality (p=0.029 and p=0.02), the frequency of hospitalizations not related to cardiovascular disease (p=0.02), less non-fatal cardiovascular events (p=0.04).

CONCLUSION: In patients with heart failure, the presence of chronic obstructive pulmonary disease increased the risk of death from all causes by 2.07 times, cardiovascular mortality by 2.24 times, and achieving the combined endpoint by 1.68 times. Regression models were developed to determine the probability of risk of death from all causes and cardiovascular death.

BACKGROUND: Damage to the kidney parenchyma of various origins is associated with the accumulation of extracellular matrix proteins, the regulation of which involves the matrix metalloproteinase/inhibitor system.

AIM: To evaluate the pathogenetic role of the proteinase/blood inhibitor system in experimental renal tuberculosis.

MATERIAL AND METHODS: When modeling the process, a clinical strain 5582 of the Beijing genotype with multidrug resistance of mycobacteria was used. The study was conducted on 20 rabbits, divided into three groups: the first (n=6) included infected untreated animals; in the second (n=7) and third (n=7) anti-tuberculosis therapy was administered orally for 18.5 weeks; in the third, treatment was carried out in combination with a single injection of autologous mesenchymal stem cells into the ear vein. Blood levels of matrix metalloproteinases-1 and -9, tissue inhibitor of metalloproteinases-1, cystatin C and neutrophil elastase were determined. Morphological changes in the kidney parenchyma at the end of the experiment were assessed using 26 indicators, including tubulointerstitial and vascular changes. The median and interquartile ranges were calculated, the Kruskal–Wallis test, analysis of covariance, and the projective classification method were used.

RESULTS: The progression of kidney tuberculosis was accompanied by a significant increase in the level of neutrophil elastase by 1.9 times, matrix metalloproteinase-9 by 2.2 times, and cystatin C by 1.5 times compared to the initial level. The treatment carried out in the second and third groups contributed to the normalization of these indicators. The concentrations of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in all three groups did not change relative to the baseline level. Covariance analysis showed that in the pathogenesis of renal tuberculosis changes in matrix metalloproteinase-1 (p=0.003), matrix metalloproteinase-9 (p=0.002), tissue inhibitor of metalloproteinases-1 (p=0.01) and cystatin C (p=0.0001) were primarily associated with vascular changes, found in all study groups. A linear combination containing three morphological characteristics allowed us to identify differences between the three groups with 90% accuracy.

CONCLUSION: Renal tuberculosis, caused by a multidrug-resistant pathogen, is characterized by an imbalance in the proteinase/inhibitor system and impaired renal function, the degree of which is associated with the morphological characteristics of vascular and tubulointerstitial changes.

Over the past decade, the prevalence of metabolic syndrome has increased significantly worldwide, and in most countries around the world this non-communicable disease has become a major health threat. Today, the mechanisms of metabolic syndrome influence on the development of various pregnancy complications are actively discussed. Studies of the pathophysiological mechanisms of the relationship between metabolic disorders and placental-associated pregnancy complications deserve special attention. The placenta performs essential functions throughout pregnancy and serves as a site for nutrient exchange and gas exchange between the pregnant woman and the fetus. Metabolic changes in women are closely associated with a number of placentally mediated obstetric complications, including preeclampsia, placental insufficiency, macrosomia, fetal growth restriction and antenatal fetal death. It is believed that it is in the first trimester of pregnancy that trophoblast cells are most sensitive to metabolic changes in homeostasis, which leads to their ischemia, impaired proliferation, invasion and angiogenesis. In pregnancies complicated by metabolic syndrome, the placenta is exposed to inflammation, oxidative stress, dyslipidemia, hyperglycemia, and altered hormone levels. Such metabolic changes can affect the development and function of the placenta, leading to abnormal fetal growth, as well as metabolic and cardiovascular disorders in children in the long term. Despite the wide range of pregnancy complications with metabolic syndrome, the mechanisms of their development have not been sufficiently studied. The purpose of this review was to summarize current knowledge about the pathophysiological mechanisms of the influence of metabolic syndrome on the development and function of the placenta.

Alzheimer’s disease is a neurodegenerative disease characterized by progressive neurocognitive dysfunction. Today, studying the pathogenesis of this disease remains an urgent problem. The review describes the pathogenetic basis of Alzheimer’s disease, including not only extracellular deposition of amyloid plaques and intracellular hyperphosphorylation of tau protein with subsequent formation of neurofibrillary tangles, but also mitochondrial dysfunction, impaired autophagy, neuroinflammation, etc. Data are presented on the effect of hyperphosphorylated tau protein on the breakdown and enhancement of β-amyloid peptide synthesis. Oligomerized tau protein causes proteasomal dysfunction and oxidative stress. Mitochondrial dysfunction is closely related to oxidative stress, which can be both a cause and a consequence. Autophagy, namely mitophagy, in turn, also plays an important role in the development of mitochondrial dysfunction. It can be argued that neuroinflammation is associated with all of the listed links in pathogenesis. This review also examines the influence of intestinal dysbiosis on the development of the disease. The complex mutual influence of pathogenetic mechanisms forms a multicomponent network of pathological processes. Understanding the Alzheimer’s disease pathogenesis is necessary in the search for methods for correcting impaired functioning mechanisms of the nervous system, which will help develop effective methods for treating this disease. In addition, to better understand the mechanisms of Alzheimer’s disease development, it is necessary to search for common pathogenetic factors with other neurodegenerative diseases.

The structural integrity of the skeleton is ensured by the constant remodeling of bone tissue, which is based on the functioning and interaction of osteolytic cells (osteoclasts) and bone tissue forming cells (osteoblasts/osteocytes). Despite the general understanding that the degree of mineralization of the bone matrix determines the fragility of the skeleton, there is currently insufficient information about its age-related changes associated with the functioning of these cells. The purpose of the review is to evaluate existing data on age-related bone changes associated with the functional state of mesenchymal stem cells, osteoblasts/osteocytes and osteoclasts. Inclusion criteria: randomized or non-randomized controlled studies examining age-related bone change. A search for studies in the field of bone tissue condition was carried out in electronic scientific databases Google Scholar, Medline, PubMed, Scopus, Web of Science and Cochrane Library by keywords and their combinations using the AMSTAR 2 program. The selection of publications (59 out of 680 included) was carried out randomly, after which three authors independently assessed their methodological quality. The main pathogenetic mechanism involved in bone loss with age is a decrease in the formation of osteoblasts with impairment of their ability to osteogenic differentiation. Osteocytes in old age are subject to excessive and prolonged stress, which causes unbalanced autophagy and apoptosis, which leads to changes in their ability to deposit and mineralize extracellular organic matrix. With age, accelerated osteoclastogenesis occurs, mediated by osteoblasts, which leads to increased expression of certain receptors at the level of bone stromal cells and osteoblasts. The presented literature data demonstrate convincing evidence that an increase in bone resorption due to complex metabolic processes with age occurs against the background of an increase in the number and activity of osteoclasts, apoptosis of osteoblasts with a decrease in their metabolic activity, as well as a redistribution of osteogenic differentiation of mesenchymal stem cells towards adipocytes. The results presented in the review can be used as a basis for developing diagnostic criteria for identifying senile osteoporosis and the risk of fractures.

The article shows a clinical case of an extremely rare complication after laparoscopic cholecystectomy — a giant subcapsular hematoma of the liver. The clinical, laboratory and instrumental data of the patient and the results obtained were analyzed. Analysis of the data from the operated patient did not reveal the main reason that could have caused the development of a giant subcapsular hematoma of the liver. The patient had no bleeding disorders, had not previously suffered any bleeding, and did not take anticoagulants as an outpatient. During the operations, no source of bleeding or damage to the liver parenchyma was identified. In addition, there was no evidence of focal liver lesions according to the preoperative ultrasound scan. Outpatient use of a drug from the group of antiplatelet agents, as well as short-term irregular use of analgesics to relieve periodic pain could provoke the development of this complication. Treatment of subcapsular hematoma of the liver mainly depends on the clinical condition of the patient and the size of the hematoma. With conservative management, the condition of the formed hematoma should be more carefully monitored over time using radiation diagnostic methods. If necessary and according to indications, do not exclude possible repeated laparoscopic intervention, including conversion to laparotomy, taking into account the data of clinical, laboratory and radiological research methods. In most cases, this condition requires conservative treatment. Patients with such a complication require careful hemodynamic monitoring and visual monitoring of the complications development. Probably, preference should be given to magnetic resonance imaging, since this method is the most objective and does not carry a radiation load. The main task is not to miss the moment of hematoma rupture and the development of fatal bleeding.

The article presents for the first time a complete scientific biography of Gilarii-Zdislav Ivanovich Vilga, created on the basis of archival and literary sources of the early twentieth century. G.I. Vilga was a recognized founder of Russian forensic dentistry and one of the founders of Russian maxillofacial surgery. However, his services to domestic dentistry were not limited to this. Signs of the institutionalization of dentistry in Russia at the end of the 19th and beginning of the 20th centuries were the reform of education (private dental schools, the first departments of odontology at universities), the emergence of specialized societies, congresses and the press. Professor G.I. Vilga was one of the first private assistant professors of odontology at Moscow University, the founder of the Moscow dental school and its head, chairman of the Moscow Odontological Society and editor of its printed organ, board chairman of the Russian Dental Union and two All-Russian Dental Congresses. All this gives us the right to consider him one of the founders of domestic dentistry.

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Franco JVA, Bongaerts B, Metzendorf MI, Risso A, Guo Y, Peña Silva L, Boeckmann M, Schlesinger S, Damen JAAG, Richter B, Baddeley A, Bastard M, Carlqvist A, Garcia-Casal MN, Hemmingsen B, Mavhunga F, Manne-Goehler J, Viney K, Bellorini J. Undernutrition as a risk factor for tuberculosis disease. Cochrane Database of Systematic Reviews. 2024. Issue 6. Art. No. CD015890. doi: 10.1002/14651858.CD015890.pub2