Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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Popova ES, Agbalyan AN, Titov VD, Moiseeva VP, Mashin SV, Anfimiadi VA, Zhukov GM, Bondarevskaya AO, Gavrilyuk LM

Currently, the occurrence of multiple primary malignant tumors is one of the complex and poorly understood issues of oncology. After the diagnosis of malignant neoplasm is established, the risk of a new primary, non-metastatic tumor increases in a patient. The paper presents a case report of the patient with four multiple primary malignant tumors in the duodenum and colon. Synchronous cancer of the cecum and rectosigmoid junction occurred after 9 months of the duodenal cancer pancreatoduodenal resection, photodynamic therapy, and 12 multiagent chemotherapy courses. The patient received 8 courses of chemotherapy with capecitabine, during which cancer progression was reported, and 16 multiagent chemotherapy courses. Two years later rectal cancer occurred, due to which rectal re-resection was conducted, along with 4 multiagent chemotherapy courses and target therapy. This clinical case emphasizes that it is necessary to perform additional assessment when treating patients with synchronous or metachronous multiple primary tumors to ensure the timely diagnosis and multidisciplinary approach to treatment of cancer patients.

Received: 2025-04-07

Published online: 2025-05-27

DOI: 10.24075/brsmu.2025.028

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VIEWS 496

Kiseleva VV, Vishnyakova PA, Kosyreva AM, Kananykhina EYu, Emelianov II, Elchaninov AV, Fatkhudinov TH

High fatality rate and the lack of pathophysiological therapy are typical for acute respiratory distress syndrome (ARDS). Intratracheal lipopolysaccharide (LPS) administration is used to model ARDS in animals. The method has the limitation of requiring the use of equipment to perform intubation and control the animal’s state. The study aimed to assess the possibility of using intranasal LPS administration instead of intratracheal and determine the LPS optimal dose. A total of 150 mL of the E. coli O111:B4 LPS (7.5 mg/kg or 15 mg/kg) or 0.9% NaCl was administered to 21 Sprague-Dawley rats. After 48 h blood was collected from the tail vein to determine the white blood cell count and TNFa concentration. The lungs were retrieved to assess dry weight (wet/dry ratio) and to determine the expression of the genes encoding pro- and anti-inflammatory cytokines using real-time PCR. The relative counts of CD68-, CD86-, and MHC II-positive cells in the lung tissue were also evaluated using flow cytometry. The w/d ratio was higher when the dose of 15 mg/kg of body weight was used (p = 0.0228, ordinary one-way Anova). Вlood lymphocyte counts were decreased (p = 0.0019, ordinary one-way Anova), and neutrophil counts were increased (p = 0.0021, ordinary one-way Anova) upon administration of both doses. The counts of CD86- (p = 0.0014, ordinary one-way Anova) and MHC II-positive cells (p = 0.0050, ordinary one-way Anova) increased after LPS administration. The IL10 gene expression was significantly increased upon administration of the dose of 15 mg/kg (p = 0.0024, ordinary oneway Anova), while the IL4 expression (p = 0.0194, ordinary one-way Anova) was decreased upon administration of the dose of 7.5 mg/kg. Thus, intranasal LPS administration can be used to model ARDS in the Sprague-Dawley rats. Administration of the high dose leads to the rapid development of inflammation in the lung.

Received: 2025-04-21

Published online: 2025-05-20

DOI: 10.24075/brsmu.2025.027

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VIEWS 580

Popov NS, Terekhov VM, Baranov MS, Balabanyan VYu, Kaurova DE, Myasnyanko IN, Terekhova EA

Assessment of pharmacologically active molecule biotransformation represents the most important phase of drug development, the results of which make it possible to identify active and toxic metabolites and provide a fundamental basis for the targeted design of new candidate drug molecules. The liver is the main organ involved in biotransformation of drugs. The currently widely used in vitro metabolism assessment methods do not allow one to identify products of extrahepatic drug molecule biotransformation. The study aimed to develop an in vivo approach to determination of the role of the liver in biotransformation of candidate drug molecules. The approach proposed is based on the vascular liver isolation performed surgically in laboratory rats. The organ involvement in biotransformation of pharmacologically active molecules is exemplified by the leader compound of the sydnone imine group possessing vasodilatory activity. It has been shown that elimination of the liver from systemic blood flow does not result in generation of the test compound metabolites identified by chromatography–mass spectrometry. The findings can provide the basis for prediction of drug pharmacokinetics, efficacy, and safety.

Received: 2025-04-16

Published online: 2025-05-15

DOI: 10.24075/brsmu.2025.026

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VIEWS 517

Rebrikov DV, Degtyareva AV, Yanushevich YuG, Gautier MS, Gorodnicheva TV, Bavykin AS, Ushakova LV, Filippova EA, Degtyarev DN, Sukhikh GT

Crigler–Najjar syndrome type I, an orphan UTG1A1 enzyme deficiency, manifests at birth with severe unconjugated hyperbilirubinemia. Here we describe sustained clinical response in a pediatric patient with Crigler–Najjar syndrome type I treated with two consecutive doses of AAV8 delivering the UTG1A1 coding sequence. Infusion I (6 × 1012 vg/kg) afforded sustained decrease in serum bilirubin, allowing substantial relaxation of the phototherapy from 12 h to 4 h daily. Infusion II at a double dose was made in 6 months; the decision was intended at complete elimination of phototherapy. However, the elimination led to a sharp increase in bilirubin levels necessitating resumption of phototherapy. The patient is currently stable on 4 h daily phototherapy for 80 weeks since the resumption and 107 weeks since the AAV8 therapy initiation. No toxic side effects were encountered. A slow incremental dynamics in serum bilirubin opens the issue of clinical advisability for subsequent infusions of the drug.

Received: 2025-04-25

Published online: 2025-04-30

DOI: 10.24075/brsmu.2025.025

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VIEWS 561

Minasov BSh, Yakupov RR, Akbashev VN, Shchekin VS, Vlasova AO, Minasov TB, Karimov KK, Akhmeldinova AA

Morphological subchondral bone tissue alterations associated with knee osteoarthritis represent a key pathogenesis link and can precede articular cartilage destruction. The study aimed to identify typical morphological and morphometric signs of osteosclerosis and osteoporosis in the subchondral zone of the femur and tibia. Analysis of 40 bone tissue fragments collected when performing knee replacement surgery in 20 patients (12 females and 8 males) aged 58–75 years with stage III–IV osteoarthritis was performed. Histological and morphometric assessment involving the use of light microscopy and microfracture index (MFI) calculation revealed significant differences in trabecular thickness, intertrabecular distance, and the degree of microdamage between the sites of sclerosis and osteoporosis. High MFI values in the zones of osteoporosis can reflect reduced subchondral bone strength. The findings confirm the diagnostic value of the subchondral zone morphometry and the prospects of using MFI as a quantitative risk criterion when planning orthopedic treatment.

Received: 2025-04-06

Published online: 2025-04-30

DOI: 10.24075/brsmu.2025.024

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VIEWS 572

Kildyushevsky AV, Kotov SV, Sidorova OP, Borodin AV, Bunak MS

Multiple sclerosis is an autoimmune disorder, the development of which involves humoral and cellular immunity. The disease-modifying drugs (DMDs) for multiple sclerosis slow down the disease progression, but the therapy prescribed is not always well tolerated by patients; allergy and other side effects are possible. In this regard, the development of new methods, including non-pharmacological ones, is relevant. These methods include extracorporeal photopheresis involving UV exposure of peripheral blood lymphocytes and its modification — transimmunization (involving incubation of lymphocytes after UV exposure). The study aimed to compare and within a year assess the transimmunization and glatiramer acetate efficacy in patients with relapsing-remitting multiple sclerosis. A total of 19 adult patients with relapsing-remitting multiple sclerosis, who had been prescribed transimmunization, were assessed. Patients over the age of 18, who did not receive treatment by other methods (DMDs for multiple sclerosis, etc.), were included in the study. The comparison group consisted of 48 adult patients with relapsing-remitting multiple sclerosis, who were prescribed subcutaneous glatiramer acetate 20 mg daily. Clinical assessment was performed using EDSS. Brain and spinal cord MRI was performed in the 3.0 and 1.5 T scanners. When performing transimmunization, the decrease in the median overall EDSS score from 2 to 1.5 points was reported. In the comparison group of patients receiving glatiramer acetate, the median EDSS score changed from 1.75 to 2 points. Therefore, transimmunization is comparable with first-line DMDs for multiple sclerosis and can be used to stabilize the disease course.

Received: 2025-04-02

Published online: 2025-04-29

DOI: 10.24075/brsmu.2025.023

Comments 0

VIEWS 523

Ivanenko AV, Starodubova VD, Shokhina AG

Wilson’s disease is a rare hereditary disorder caused by the ATP7B gene mutations that leads to copper metabolism disturbances and toxic copper accumulation in the liver, brain, and other organs. The main manifestations include liver damage, neurological and psychiatric symptoms. The use of advanced treatment methods (D-penicillamine, trientine, zinc salts) improves the outcome, but is limited by side effects and complexity of adherence to therapy. Liver transplantation is used in severe forms, but it is limited by the donor shortage and the need for immunosuppression. In our opinion, promising areas include gene therapy involving the use of AAV vectors and CRISPR/Cas9, mRNA platforms, and cell technologies. However, these approaches require further research for the efficacy, safety, and accessibility improvement.

Received: 2025-04-02

Published online: 2025-04-28

DOI: 10.24075/brsmu.2025.022

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VIEWS 510

Nikishina VB, Petrash EA, Chausov AS, Kanimetov KK

The relevance of the study provided results from the need to search for the objectifying methods to assess self-identification phenomenon in early childhood. The study aimed to evaluate the diagnostic potential of the software-hardware complex for analysis of self-identification phenomenon in young children. The sample consisted of 136 subjects of early age (12–36 months): 57 boys and 79 girls. Assessment methods: functional neuropsychological tests for evaluation of facial and optical-spatial gnosis; test 22 — mirror image series of the Bayley-III cognitive scale; self-recognition mirror test; the developed software-hardware complex for analysis of self-identification phenomenon in early childhood (SHC). The study conducted has shown that self-identification emerges at the age of 18 months, which has been also confirmed by the earlier research. However, the response to one’s own reflection in the mirror as one sign of self-identification manifests itself in children at an earlier age and in some children turns out to be shaped by the age of 12 months, which is suggested by the facts of successful test execution in the group aged 12–17 months and low specificity of the method for self-identification. Thus, high SHC specificity for self-identification in early childhood is reported based on the findings.

Received: 2025-03-28

Published online: 2025-04-25

DOI: 10.24075/brsmu.2025.021

Comments 0

VIEWS 468