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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Stetsenko IF, Krasnenko AYu, Stanoevich US, Mescheryakov AA, Vorotnikov IK, Druzhilovskaya OS, Belova VA, Churov AV

Breast cancer is one of the most widespread forms of solid tumors. By analyzing the traits of breast cancer pathogenesis at the molecular level using modern genetic analysis techniques and at different stages of the disease new data can be obtained to be further utilized in clinical practice. Molecular profiling based on next-generation sequencing is being increasingly applied as a clinical test to select target drugs for treating breast cancer patients with tumors highly resistant to therapy. In this study, we performed targeted sequencing of BRCA1 and BRCA2 oncogenes. In the total of 66 DNA samples from patients with breast tumors, BRCA1/2 mutations were found in 39 patients. There were 78 unique genetic variants, including 30 mutations in BRCA1 and 48 mutations in BRCA2. We identified 33 mutations affecting the sites of post-translational modification in proteins (PMT mutations).

Received: 2018-12-03

Published online: 2018-12-25

DOI: 10.24075/brsmu.2018.074

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VIEWS 3552

Istomina MS, Pechnikova NA, Korolev DV, Pochkayeva EI, Mazing DS, Galagudza MM, Moshnikov VA, Shlyakhto EV

In recent years there has been an increase in interest in the use of colloidal quantum dots (QDs) in biology and medicine. In particular, QDs can be a perspective nanoscale object for theranostics, in which due to the specific accumulation of drug-loaded QDs in the pathological focus, its simultaneous visualization and targeted therapeutic influence occur. One of the serious limitations of the use of QDs in medicine is their potential toxicity, especially when the nanocrystal material contains elements such as cadmium or plumbum. Therefore, it is promising to develop labels based on QDs of relatively less toxic semiconductors of group I-III-VI, such as CuInS2 and AgInS2. In this study, biodistribution and biocompatibility of QDs based on the AgInS2 compound with a ZnS shell (ZAIS) are considered. In the study of biodistribution, the accumulation of QDs in organs such as liver, lungs, heart and kidneys was revealed. It was shown that QDs in the dose range from 2 • 10–7 to 4 • 10–6 M/L at intravenous administration in rats does not have a significant effect on body mass dynamics and basic hematological parameters for 30 days. Thus, ZAIS QDs can be used to visualize tissues and organs in various pathological processes, and immobilization of the drugs on their surface will allow to approach their application for theranostics.

Received: 2018-07-28

Published online: 2018-12-24

DOI: 10.24075/brsmu.2018.073

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VIEWS 3567

Kapitonova MYu, Alyautdin RN, Wan-Syazli RWAL, Nor-Ashikin MNK, Ahmad A, Norita S, Dydykin SS

Parkinson disease is one of the common age-related motor neurodegenerative diseases, in which dopamine neurons degeneration is considered to be pathognomic for the development of motor disfunction. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which is considered to be a key regulator of neuronal plasticity. BDNF, being a large molecule, does not pass through the blood-brain barrier (BBB). Synthetic polymer nanoparticles (NP), covered by surfactant, provide the phenomenon of “Trojan hoarse” and enable BDNF to penetrate into the brain tissue. For modelling of parkinsonism we used an intraperitoneal (i.p.) injection of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which was injected to the C57BL/6 mice with subsequest treatment with normal saline (group 1), BDNF (group 2), nanoparticulate BDNF (group 3) and surfactant-coated nanoparticulate BDNF (group 4). After 90 min, 24 hours, 72 hours and 7 days manifestations of parkinsonism were evaluated using behavioural tests of open field, rota-rod, assessment of the tremor, length of the body and pace. At the end of experiment the brain was sampled for histological evaluation of changes in the striatum and midbrain and concentration of BDNF in the brain tissues. The results of the experiments demonstrated that nanoparticulate BDNF covered with surfactant significanltly reduced rigidity of the skeletal muscles, oligokinesia and tremor, and also significantly increased BDNF concentration in the brain tissues.

Received: 2018-07-09

Published online: 2018-12-23

DOI: 10.24075/brsmu.2018.072

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VIEWS 3511

Shibaeva AV, Pozdniakova NV, Spiridonov VV, Smirnova MS, Korman DB, Ostrovskaya LA, Abzaeva KA, Belyakova AV, Biryukova YuK, Zylkova MV, Ivanov KP, Shevelev AB, Kuzmin VA

Aurumacryl is an incomplete metal salt of poly(acrylic acid) that exhibits hemostatic activity and inhibits the growth of transplantable carcinomas in vivo. The samples of aurumacryl synthesized following the original technique are insufficiently soluble, which complicates the study of the mechanisms involved in their synthesis and underlying their cytotoxic effect. The aim of this work was to study the impact of the following factors on aurumacryl properties: the molecular weight of the polyacrylate polymer in a range between 2 and 1,000 kDa, the presence of a counterion H+ or Na+, the molar ratio of AuCl– to the polyacrylate polymer (1 : 5 and 1 : 10), the total concentration of the polyacrylate polymer during synthesis (0.1 and 3%), and the type of drying (lyophilization). By comparing the cytotoxicity of aurumacryl samples with significantly different molar ratio of gold ions to the polyacrylate polymer against human breast carcinoma cells (MCF-7), we established that the proportion of the polymer and its molecular weight in the sample do not affect the biological properties of the synthesized substance. Using UV spectroscopy, we revealed that the concentration of Au (III) ions in aurumacryl determines its cytotoxicity.

Received: 2018-09-28

Published online: 2018-12-16

DOI: 10.24075/brsmu.2018.071

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VIEWS 3450

Kopetskiy IS, Virgilyev PS, Pobozhieva LV, Stupakov IN

Today, a dentist can make use of any of the multitude of methods to forecast treatment effectiveness, restoration lifetime, new caries lesions development risks. However, at the national level we see no studies dedicated to evaluation of clinical effectiveness of the majority of those methods. Having analyzed the available literature, we selected CAMBRA caries development risk assessment method and made it a goal of this study to evaluate its effectiveness while also seeking to develop the most effective treatment plan. We examined 126 young adults without concomitant somatic pathologies and divided them into treatment and control groups; treatment group was then further subdivided into 3 groups depending on the risk of caries development. All patients had their teeth and tissues of the oral cavity treated following the developed and the classic plans, accordingly. After 12 months, follow-up examinations of the treatment group revealed new caries lesions in 34 (43.5%) patients, while 40 (51.3%) were diagnosed with periodontal diseases. In the control group, we found new cavities on the teeth of 25 (52.1%) patients and periodontal pathologies in 28 (58.3%) study participants. This research shows that CAMBRA and the developed treatment plan can decrease the rate of caries development in young adults.

Received: 2018-07-04

Published online: 2018-12-16

DOI: 10.24075/brsmu.2018.070

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VIEWS 3484

Solodova RF, Tolstykh MP, Isaev TK, Trushkin RN, Vtorenko VI, Staroverov VM, Sokolov ME

Palpation is one of the classic examination methods in open surgeries. In minimally invasive surgery, intra-operational manual palpation is impossible to use for assessing tactile characteristics of tissues. In Russia, the only available instrument for intra-operational assessment and objective registration of tissue visco-elastic properties is the Medical Tactile Endosurgical Complex (MTEC). The aim of this work was to study the performance of MTEC in renal surgery. The study was performed during nine elective laparoscopic surgeries for clear cell renal carcinoma and simple renal cysts. We have found several differences in the use of MTEC in renal surgery, as compared to its use in gastrointestinal or lung surgeries. The key factor determining these differences was the inverse relations between tissue visco-elastic properties: the studied tumors were softer than the surrounding tissue. Detection of intraparenchymal tumors by tactile methods was impossible. For surface tumors, in one case out of nine it was possible to strictly locate the border of the tumor by tactile examination. We were able to quantitatively assess and determine the difference in hardness of tumors and intact tissue using MTEC. This allows studying the prognostic value of objectively registered tactile characteristics of renal tumors.

Received: 2018-07-26

Published online: 2018-12-16

DOI: 10.24075/brsmu.2018.069

Comments 0

VIEWS 3415

Sychev DA, Minnigulov RM, Ryzhikova KA, Yudina IYu, Lychagin AV, Morozova TE

Rivaroxaban is a safer and more effective alternative to warfarin. However, there are reports of some cases of major hemorrhagic complications associated with rivaroxaban that significantly impair the patients' quality of life and can lead to a fatality. Personalized therapy, including pharmacogenetic testing, may help prevent such adverse events. This study aimed to investigate how ABCB1 3435C>T (rs1045642) and CYP3A5 6986A>G (rs776746) gene polymorphisms, when carried by a patient taking rivaroxaban to prevent thrombosis after total hip or knee replacement surgery, affect prothrombin time (PT). Sixty-five patients participated in the study. Their genotypes were identified by PCR in real time. To learn PT peculiar to each patient, we collected venous blood on the 5th day of their anticoagulation therapy, 1 hour before they took rivaroxaban and 3 hours after. Having calculated %ΔPT, we divided the patients into 2 groups: 1) %ΔPT ≤ 0 (n = 7; 10.8%); 2) %ΔPT > 0 (n = 58; 89.2%). Regarding the distribution of rs1045642 polymorphism, we determined the difference between the groups to be statistically significant (χ2 = 6.64; p = 0.027). As for rs776746 polymorphism, the difference was insignificant (χ2 = 0.101; p = 1.0). We discovered that rs1045642 polymorphism has a significant effect on PT variance in patients taking rivaroxaban to prevent thrombosis after total hip or knee replacement surgery.

Received: 2018-10-08

Published online: 2018-12-15

DOI: 10.24075/brsmu.2018.068

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VIEWS 3808

Moiseev AB, Mironov AA, Kolbe OB, Vartapetova EE, Polunina VV, Al Sabunchi AA, Polunin VS, Buslaeva GN

Pediatric urinary disorders manifested as urinary incontinence, compelling urges to urinate, etc. remain an important problem of contemporary healthcare. In spite of being extensively covered in the literature, urinary disorders, including enuresis, still present a diagnostic challenge to the physicians of primary healthcare facilities. Based on the findings of our retrospective study that revealed discrepancies between referral and final diagnoses of pediatric urinary disorders, we give recommendations to both physicians of primary healthcare facilities and their inpatient care colleagues that will help them to arrive at the correct diagnosis of a urinary disorder or concomitant bladder-bowel dysfunction using the proposed diagnostic algorithm.

Received: 2018-06-19

Published online: 2018-12-12

DOI: 10.24075/brsmu.2018.067

Comments 0

VIEWS 3615