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Journal of Siberian Medical Sciences

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No 4 (2025)
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ORIGINAL RESEARCH

7-14 14
Abstract

Introduction. The high prevalence of gastric ulcer, as well as its multiple etiologies substantiate the urgency of developing new drugs effective in this condition. Previously, the antiulcer effect of the tripeptide Leu-Ile-Lys (LK-3) was revealed under experimental conditions in gastropathies of various origins. To clarify the mechanism of action of this compound, an in-depth experimental study of its effects on the gastric mucosa (GM) is necessary.

Aim. To study the effect of the tripeptide LK-3 on GM under experimental conditions.

Materials and methods . The experiment was performed on 16 Wistar rats. All animals were divided into two groups: the intact group and the group with intragastric administration of the tripeptide LK-3 (for 7 days, 11,5 mg/kg). Pathomorphological examination of the stomachs of experimental rats was performed. A histological picture of the GM was examined, and its thickness was measured. In addition, the density and composition of the inflammatory infiltrate, as well as the DNA replication index in the nuclei of cervical GM cells were determined.

Results . During gross and microscopic examination, no pathological changes in the GM were revealed in either experimental group. The tripeptide LK-3 administration caused a statistically significant increase in GM thickness, by 1,4 times, compared to the intact group. In addition, the DNA replication ratio in cervical GM cells in rats treated with LK-3 was 1,2 times higher than in intact animals. At the same time, 100% of the cells studied were in the S-phase of the cell cycle after administration of LK-3, compared to 75% in the intact group.

Conclusion. A 7-day intragastric administration of the tripeptide LK-3 (11,5 mg/kg) to rats caused an increase in GM thickness and in the proportion of cells in the S-phase of the cell cycle.

15-23 18
Abstract

Introduction. The use of direct oral anticoagulants (DOACs) in elderly patients is associated with an increased risk of complications compared to the general population. First of all, this is due to the presence of risk factors – modifiable and nonmodifiable. The main modifiable risk factors for DOAC-related hemorrhagic complications are polypharmacy and adverse drug interactions. Consideration of renal function is also important. The study of these issues is extremely important for finding a balance in the benefit-harm ratio in the treatment of elderly patients.

Aim. Assessment of risk factors for the development of DOAC-related complications in elderly patients with polypharmacy.

Materials and methods . A retrospective single-center study involved 503 patients who were followed-up for April–September 2024. Patients were treated with DOACs for persistent atrial fibrillation, while they did not have severe hemorrhagic complications (exclusion criterion). A questionnaire survey was used, during which data on medications taken, the duration of anticoagulant treatment, and renal function were collected.

Results . The independent factors associated with DOAC-related complications in the study cohort were polypharmacy (concomitant use of over 6 medications) and a reduced glomerular filtration rate of less than 45 ml/min/1,73 m2. Furthermore, a correlation between an increased risk of hemorrhagic complications and the concomitant intake of DOACs with specific drugs that affect the anticoagulant’s pharmacokinetics was identified.

Conclusion. When prescribing DOACs to elderly patients with the risk factors described above, the benefit-harm ratio for the prescribed anticoagulant should be carefully evaluated, the risk of bleeding should be predicted, and adverse drug interactions should be avoided in patients with polypharmacy.

24-35 13
Abstract

Introduction. Coronary artery disease (CAD), and acute coronary syndrome (ACS) in particular, remains the leading cause of mortality in Russia, resulting in significant socioeconomic losses. Beyond traditional risk factors, proinflammatory cytokine-related systemic inflammation and increased vascular stiff ness play a key role in the pathogenesis of adverse outcomes. Therefore, investigating the relationship between the activity of these processes, the severity of CAD, and the course of ACS in young and middle-aged patients represents a relevant and pressing, and understudied problem.

Aim. To assess the features of clinical presentation, the nature of systemic inflammation and vascular stiff ness indices in young and middle-aged ACS patients depending on the grade of coronary artery lesion.

Materials and methods . The study included 84 patients (64 men, 20 women) aged 37–60 years, hospitalized for myocardial infarction (MI) (22,6%) or unstable angina (77,4%). Based on the results of coronary angiography, patients were divided into two groups: with hemodynamically significant (>70%) – group 1 and intermediate (50–70%) or non-obstructive (<50%) coronary artery (CA) stenosis – group 2. All participants underwent testing for plasma interleukins (IL-1β, IL-6, IL-8, IL-4, and IL-10); besides, arterial stiff ness was assessed by measuring pulse wave velocity (PWV), vascular age, and cardio-ankle vascular index (CAVI).

 Results. Patients with hemodynamically significant CA stenoses (group 1) had a more severe CAD course: myocardial infarction, multivessel CAD, and percutaneous coronary interventions were significantly more common. Obesity and chronic kidney disease were also more common in this group. Patients in group 2 had higher IL-8 concentrations, while those in group 1 had higher IL-6 concentrations. Vascular stiff ness indices (PWV and CAVI) did not diff er significantly between the groups; however, a trend toward a lower vascular age compared to the chronological age was revealed in group 2.

Conclusion. Specific markers associated with the severity of CA lesion were identified in young and middle-aged patients with ACS. Patients with hemodynamically significant stenoses had a relative increase in IL-6 levels, while those with intermediate and non-obstructive stenoses had significantly elevated IL-8 levels.

36-45 11
Abstract

Introduction. Pharmacokinetic (screening) studies are particularly relevant for the development of new substances and drugs. These studies investigate the basic processes such as absorption, distribution, metabolism and elimination (ADME) of a pharmaceutical substance. Pharmacokinetic parameters are of key importance to clinicians, as they provide data necessary for determining optimal dosages.

Aim. To study the pharmacokinetic characteristics of a new substance of the water-soluble sulfur-containing antioxidant potassium 3-(4-hydroxy-3,5-dimethylbenzylthio) propionate (TF-7).

Material s and methods . A TF-7 solution was administered to rats intragastrically at a dose of 500 mg/kg. Blood samples were collected 1,5, 3, 5, 8, and 12 h after administration of the substance. The TF-7 concentration was measured using stripping voltammetry. Calculations of pharmacokinetic parameters were performed using the single-compartment pharmacokinetic model – by the classical method according to Kholodov and using the Borgia 1.03 program.

Results . The main pharmacokinetic parameters of the new TF-7 substance were calculated including half-life (t1/2), elimination rate constant (kel), total clearance (Clt), effective concentration (Ceff ), and volume of distribution (Vd).

Conclusion. The study showed rapid (t1/2) and effective distribution (Ceff , Vd) of TF-7 in the body, which ensures its ability to interact with all cellular and tissue structures. The half-life of TF-7 ranges from 1 to 1,5 h, indicating both a rapid onset of pharmacological effect and quite rapid elimination from the body.

46-60 9
Abstract

Introduction. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder of sweat glands marked by alternating periods of improvement and flare-ups. It is a serious skin condition that profoundly affects well-being of individuals with HS.

Aim. To analyze demographic and clinical profiles of patients with HS.

Materials and methods . The demographic and clinical profiles of 200 HS patients were analyzed, potential key risk factors were identified, and treatment patterns, including medical, surgical, and combination therapies, were examined. Using a quantitative approach and SPSS version 27, statistical analyses (correlation, frequency, regression, and ANOVA) of data obtained during a standard survey were conducted.

Results . A strong association between the HS severity and clinical characteristics (HS duration, hospitalization and comorbidities), as well as potential risk factors (psychological, genetic and lifestyle influences) were determined. Also, it was shown that patterns of treatment significantly affect the symptom management and quality of life.

Conclusion. The findings underscore the need for a comprehensive understanding of demographics and clinical profiles in HS and using tailored treatment approaches to improve outcomes and quality of life of HS patients.

61-79 10
Abstract

Introduction. Tick-borne encephalitis (TBE) is a transmissible disease endemic for the Novosibirsk region (NR). The incidence of TBE in the NR is 2,7–5,8 times higher than the Russian average. Despite the fact that the infection is vaccine-preventable, fatal cases are recorded in the NR year after year. Western Siberia is characterized by the circulation of the Siberian subtype of the virus, which affects the central nervous system (CNS) in two-thirds of cases, and in 20–30% of cases, manifestations are focal, with a high risk of mortality or permanent disability.

Aim. To analyze cases of TBE in patients of Novosibirsk City Infectious Diseases Clinical Hospital No. 1 (CIDCH) and to establish factors influencing the form and severity of the disease in unvaccinated patients, as well as predictors of the early prognosis of unfavorable severe TBE.

Materials and methods . Clinical, epidemiological, and laboratory data were analyzed in 68 patients diagnosed with TBE, hospitalized at CIDCH in 2024. Febrile TBE was recorded in 32% of patients, meningeal TBE – in 41,5%, and focal TBE – in 26,5%. The diagnosis of TBE was verified by detecting immunoglobulin M and G antibodies to the TBE virus using enzyme-linked immunosorbent assay. The results of a complete blood count (CBC), biochemistry for inflammatory markers, and cerebrospinal fluid analysis were estimated in all patients, as well as levels of serum and cerebrospinal fluid of interleukin-6 (IL-6) and ferritin were measured.

Results . The average age of patients with the febrile form of TBE was 48 ± 4,2 years. All patients had fever and intoxication. The CBC showed leukocytosis in 27,3% of patients, and absolute lymphopenia in 36,3%. Elevated C-reactive protein (CRP) levels were found in more than half of patients (54,5%). The average age of patients with the meningeal form of TBE was 50,3 ± 5,4 years. The majority of patients (86%) had high fever, while low fever was observed in 4 patients. Severe intoxication and general cerebral syndromes were detected in 93% of cases; the cerebrospinal fluid analysis revealed lymphocytic pleocytosis in 83,3% of patients – from 16 to 648 cells/ml. Leukocytosis was found in 57% of cases, and absolute lymphopenia – in only 14,3% of patients. An increase in CRP values   was observed in 13 people, and ferritin – in only 4 people. Among patients with focal forms of TBE, men predominated (77,8%); the average age was 49,7 ± 5,1 years. The meningoencephalo-poliomyelitic form of TBE was diagnosed in 61,1% of patients, while the rest had the meningoencephalitic form of TBE. A fatal outcome was recorded in 3 patients. The CBC revealed leukocytosis in 89% of cases, and absolute lymphopenia in 33%. CRP and ferritin levels were elevated in only half of the patients. Lumbar puncture results revealed pleocytosis – from 100 to 537 cells/μl, neutrophilic in 27,8%. Cerebrospinal fluid IL-6 was significantly elevated – up to 600–800 pg/ml.

Conclusion. In unvaccinated patients with TBE, age, time limits for seeking medical care, leukocyte count, lymphopenia, peripheral blood hematocrit, and CRP levels did not correlate with disease severity. Duration and grade of fever, as well as leukocytosis and blood IL-6 levels differed significantly between patients without and with CNS involvement. Pleocytosis levels   were significantly higher in patients with focal TBE. Increased cerebrospinal fluid IL-6 levels were observed in severe cases, as well as a direct correlation with pleocytosis levels, which most reliably reflects the severity of CNS involvement in TBE and may predict an unfavorable course of TBE. The identified predominance of males among patients with focal TBE, as well as late seroconversion in a significant proportion of patients, require further study in a larger patient population.

80-90 7
Abstract

Introduction. Multiple sclerosis (MS) is a major cause of disability among young people after traumatic injuries. Many studies indicate changes in the clinical picture of MS over time, which is partly attributed to the use of pathogenetic therapy.

Aim. To study the changes in the clinical picture of MS between 01.01.2003 and 31.12.2022 in Novosibirsk.

Materials and methods . 1783 patients with MS diagnosed in the period from 01.01.2003 to 31.12.2022, who lived in Novosibirsk, were included in the study. The clinical picture was described (symptoms grouped by functional systems of the Kurtzke Expanded Disability Status Scale (EDSS)); besides, the MS phenotype, EEDSS score, and whether MS disease-modifying therapies (MSDMTs) were prescribed indicating their duration, were determined. The number of symptoms at the onset (mono- and polysymptomatic) and the grade of recovery of neurological disorders were assessed. The achievement of EDSS 3,0 and EDSS 6,0 in the group of “controlled” MS was also analyzed, considering the following indices: duration of the disease (time from the onset of the clinical phase of MS to 12.31.2022), the interval “onset – EDSS 3,0”, the interval “onset – EDSS 6,0”. This group included 1494 patients who met two criteria: MSDMTs for at least 6 months, and the duration of the MS clinical phase for at least 2 years.

Results . Pathogenetic therapy of MS changed the course of the disease. The clinical picture of MS was characterized by an increase in the proportion of patients with a remitting course (from 52 to 75%, p < 0,05). The role of the gender of patients in achieving permanent disability has decreased. The onset symptoms were found to be of great importance in the long-term prognosis of persistent disability (p < 0,05).

Conclusion. Gender, age, symptoms at the MS onset, and the use of pathogenetic therapy correlate with the risk and likelihood of achieving permanent disability (p < 0,05).

91-104 10
Abstract

Introduction. Currently, the search for alternatives to conventional antibiotics, as well as for materials that do not exert an irritating effect on the body but can serve as a depot for antimicrobial substances, is highly relevant. The idea of developing a composition of a modified polyethylene glycol-based gel and an antimicrobial peptidomimetic is considered promising.

Aim. To study the physico-chemical processes of electron beam crosslinking of polyethylene glycol (PEG) in order to obtain a hydrogel with required properties and develop a depot-matrix for an antimicrobial peptidomimetic based on this technology.

Materials and methods . PEGs with a molecular weight of 400–40 000 Da was exposed to radiation, which involves polymer degradation and crosslinking. Their properties were studied, and a composition based on PEG and the antimicrobial peptidomimetic CAMP-1 (tripeptide H-Arg-Tbt-Arg-NH-C2H4-Ph) was developed.

Results . The gel was obtained using low-molecular-weight PEG and a radiation dose of 1,5–3 Mrad or high-molecular-weight PEG (over 4000 Da) and a radiation dose of 0,25 Mrad. To achieve gel formation by crosslinking, we used low-molecular-weight PEG (1,500 Da) and a radiation dose of 2 Mrad. The antibacterial peptidomimetic CAMP-1 was implanted into the gel obtained without technological complexity using a rotary homogenizer. An increase in the radiation dose led to a proportional decrease in gel flowability.

Conclusion. Varying the electron beam exposure parameters and PEG concentration allows to obtain hydrogels with the required properties for a depot-matrix intended to implant pharmacologically active agents. CAMP-1 is retained in a gel-like depot-matrix, and the diffusion of this peptidomimetic into the aqueous phase occurs at low intensity. Developing this technology of an antimicrobial drug makes it possible to produce prototypes of finished dosage forms for topical use.

105-120 7
Abstract

Introduction. Mild traumatic brain injury (mTBI) represents a critical risk factor for disrupted neurodevelopment during adolescence, particularly affecting brain regions involved in cognition and motor function. Current treatments, which are mostly derived from adult studies, highlight a gap in addressing adolescent needs, warranting the need for targeted therapeutic strategies.

Aim. This study explores the potential neuroprotective effects of tetracycline in adolescent Wistar rats following mTBI, focusing on damage to the hippocampus and cerebellar cortex. mTBI poses a significant risk to brain development in adolescents.

 Materials and methods . Fifteen rats were divided into three groups: a control group, an injury group only, and an injury group treated with tetracycline at a daily dose of 44,3 mg/kg body weight. mTBI was induced using a weight-drop method, and cognitive and motor functions were assessed through T-maze and beam-walking tests.

Results . Histological analysis using hematoxylin and eosin staining revealed that untreated rats with mTBI showed significant neural degeneration and disrupted brain architecture, alongside impaired cognitive and motor performance. In contrast, rats treated with tetracycline exhibited reduced neuronal damage and improved performance, although not fully restored to control levels. The treatment also appeared to lower inflammation and oxidative stress in the brain.

Conclusion. These findings suggest that tetracycline has neuroprotective potential in adolescent rats with mTBI, supporting its consideration as a therapeutic target for drug repurposing.

REVIEW

121-132 10
Abstract

Uterine fibroids are the most common benign monoclonal tumors in gynecological patients. This disease has a high social and economic significance, as it reduces quality of life, work capacity, and reproductive potential in women, and is the most common cause of hysterectomy worldwide. Currently, ongoing research is aimed at identifying new factors influencing the tumorigenesis and growth of fibroid nodules. However, the pathogenesis of uterine fibroids and the full range of causes underlying the variability in tumor growth remain insufficiently understood. In recent years, increasing evidence has highlighted the significant role of adipose tissue and the adipokines it produces in the development of uterine fibroids. The search for such correlations is particularly relevant in the context of the obesity epidemic in developed countries. In this context, we reviewed existing studies available on platforms such as PubMed, Scopus, eLIBRARY, and Cyberleninka, which reflect current understanding of the influence of obesity on the formation and growth of uterine fibroids.

133-144 12
Abstract

Introducing expanded neonatal screening (ENS) into medical practice in the Russian Federation (RF), in accordance with the Order of the Ministry of Health of the RF No. 274n dated 21.04.2022 “On approval of the procedure for providing medical care to patients with congenital and (or) hereditary diseases”, significantly increased the detection of hereditary metabolic diseases (HMDs) in children. However, due to several reasons, the diagnosis of orphan diseases is still fraught with great difficulties.

In this review, we present the currently available data on isovaleric acidemia/aciduria (IVA), one of the HMDs from the ENS group of diseases. The issues of epidemiology, etiopathogenesis, clinical manifestation, diagnosis and treatment of this orphan disease are considered. As an illustration of the features of medical supportive care for pediatric patients with a preliminary positive ENS for IVA, and the difficulties at the stage of verifying the diagnosis, we present a case from our own practice.

145-155 11
Abstract

Listeria (L.) monocytogenes is a Gram-positive facultative intracellular pathogen that can cause severe infections through consumption of contaminated food. The risk of developing and poor outcomes of listeriosis in pregnant women is higher than in the general population. The course and outcome of the disease are influenced not only by the host’s immune status but also by the genetic variant of L. monocytogenes and an infective dose. This article presents a brief review of the literature on listeriosis in pregnant women and a clinical case of fetal death associated with a full-blown listeriosis infection in a woman in the second trimester of pregnancy. The patient’s clinical manifestations and management are described. Symptoms of L. monocytogenes infection during pregnancy were nonspecific. Laboratory findings confirmed the infectious origin of the obstetric pathology and the severity of the infection.



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ISSN 2542-1174 (Print)