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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Khachirova EA, Samoylenko LE, Shevchenko OP

The diagnosis and treatment of patients with angiographically normal or near normal coronary arteries remains a clinically relevant problem. The aim of this study was to assess diastolic function in patients with chest pain and normal/near normal coronary arteries (NECA) using ECG-gated SPECT/CT. The study recruited 49 patients presenting with chest pain, a positive cardiac stress test and normal coronary arteries, as demonstrated by coronary angiography. All patients were ordered a myocardial SPECT/CT scan, which was performed according to a two-day protocol. After the scan, the patients were divided into 3 groups. Group 1 consisted of 17 patients with microvascular angina. Group 2 was composed of 22 patients with borderline-high blood pressure or stage I hypertensive heart disease associated with secondary microvascular dysfunction. Ten seemingly healthy individuals constituted the control group. According to coronary angiography, the controls had no cardiovascular pathologies accompanied by coronary artery disorders or impaired myocardial perfusion (SPECT). The majority of patients from groups 1 and 2 were found to have impaired diastolic function. The impairments were more pronounced in group 2 tended to exacerbate with stress. The most sensitive parameter of diastolic function, MFR/3, was outside the reference range in almost all patients in groups 1 and 2. MFR/3 characterizes the mean filling rate of the left ventricle in the first third of diastole. The control group showed no symptoms of diastolic dysfunction. Thus, the patients with chest pain, a positive stress test and NECA had signs of left ventricular diastolic dysfunction exacerbated with stress. Such patients are at risk for heart failure with preserved ejection fraction.

Received: 2018-09-17

Published online: 2019-02-23

DOI: 10.24075/brsmu.2019.001

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VIEWS 4562

Shcherbo SN, Shcherbo DS

As public health systems are being modernized across the world, conventional medicine is undergoing a serious transformation and new medical models are emerging based on personalized, predictive, participatory, precision, mobile, and digital approaches. So far, there is no consensus in the literature and the medical community about the goals, objectives and applications of these models, particularly precision medicine, which is sometimes perceived as merely a fancier term for personalized medicine. The role of laboratory diagnostics in precision medicine is also a matter of intense debate. This review analyzes the currently available information about precision medicine and gives examples of how 5P approaches can be used in clinical practice.

Received: 2019-01-30

Published online: 2019-02-14

DOI: 10.24075/brsmu.2018.095

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VIEWS 5009

Merzlyak EM, Syrko DS, Musatkina EA, Israelson MA

Recently, monoclonal antibodies (MA) have gained popularity as therapeutic agents for the treatment of autoimmune disorders. These antibodies target proinflammatory cytokines, as well as T and B cells potentially involved in the pathogenesis of such conditions. In the present work we attempt to give a systematic description of available therapeutic MA, highlight their key mechanisms of action and pinpoint their adverse effects. We believe that MA that are capable of recognizing and eliminating pathogenic T- and B-cell clones hold the most promise for medical application as biologics. Detection and identification of autoreactive lymphocyte clones is one of the most serious challenges of contemporary medicine.

Received: 2018-12-06

Published online: 2019-01-01

DOI: 10.24075/brsmu.2018.094

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VIEWS 4640

Dubovoy AV, Bervitskiy AV, Spallone A

Modern management of intracranial aneurysms is matter of great debate between supporters of “traditional” microsurgical treatment and those of relatively new endovascular management. This paper briefly reports the experience of two experienced microvascular “traditional” neurosurgeons who shares the same management philosophy favouring open microsurgery in the modern era in which endovascular management is becoming fashionable. Difficult posterior circulation aneurysms are nowadays as a rule managed endovascularly, whilst anterior circulation aneurysms can be treated with both techniques, and MCA as well as distal ACA aneurysms are better treated microsurgically. Technical refinement and — hopefully- lower cost of endovascular devices will favour a trend of prevailing use of endovascular method in the future. However the need for well-prepared microvascular surgeon will always be there, and proper training of future generations of microvascular surgeons in a setting of decreasing number of patients and open surgical casuistics represents a big challenge for the neurosurgical community, to which an answer should be given.

Received: 2018-06-28

Published online: 2018-12-31

DOI: 10.24075/brsmu.2018.093

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VIEWS 4613

Melnikova EV, Goryachev DV, Chaplenko AA, Vodyakova MA, Sayfutdinova AR, Merkulov VA

The use of nanostructured components in drug manufacturing and, more specifically, targeted drug delivery has recently become a major trend in the pharmaceutical industry. Nanodrugs encompass a wide range of pharmaceutical agents containing dendrimers, nanocrystals, micelles, liposomes, and polymer nanoparticles. Liposomes are the most well-studied nanoparticles and effective drug carriers. However, the more complex their structure is, the more process controls are needed and the more quality attributes have to be monitored, including the chemical properties of the liposomal fraction such as the shape, size and charge of the nanoparticle, conjugation efficacy, and distribution of the active ingredient. We believe that quality control of key liposome characteristics should rely on dynamic and laser light scattering coupled with electrophoresis, differential scanning calorimetry, cryo-electron microscopy, nuclear magnetic resonance, laser diffraction analysis, and gel filtration chromatography.

Received: 2018-06-29

Published online: 2018-12-31

DOI: 10.24075/brsmu.2018.092

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VIEWS 4632

Kravchenko YuE, Gagarinskaya DI, Frolova EI, Chumakov SP

Cancer immunotherapy with T-cells that carry chimeric antigen receptors is currently on cutting edge of modern oncology. Autotransplantation of T-lymphocytes with chimeric receptor specific for certain tumor antigen proves to be clinically effective, but costly. Linear carriers of chimeric antigen receptors based on natural killer NK-92 cell culture may be an affordable alternative, however, this culture is resistant to lentiviral transduction. Recently, lentiviral vectors, pseudotyped with surface glycoproteins of the measles virus vaccine strain, have recently been successfully applied for transduction of primary immune cells. The aim of the work was to assess the efficiency of transduction of NK-92 cells with lentivirus vectors, pseudotyped with measles F and H surface glycoproteins, as well as to establish optimal conditions for selection of NK-92 transduced with the chimeric receptor against CD20 and to evaluate the culture’s cytotoxic potential. The results showed that the maximum infectious titer is achieved using the H∆18 variant in combination with F∆30, and the use of the TBK1/IKKɛ inhibitor BX795 results in additional 3-fold increase in the infectious titer. CAR-expressing NK-92 were able to suppress the proliferation of CD20+ cell line Raji in lower effector-to-target ratios than unmodified NK-92.

Received: 2018-11-27

Published online: 2018-12-31

DOI: 10.24075/brsmu.2018.091

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VIEWS 4861

Kurapov PB, Bakhtenko EYu

Due to chemical stability, low toxicity, and relative simplicity of synthesis/modification techniques, gold nanoparticles (NP) enjoy a wide range of biomedical applications, including in vitro diagnostics, targeted drug delivery, contrast-enhanced radiation therapy, and photothermal therapy. The high ratio of the gold NP surface area to their volume facilitates design of complex nanoplatforms for various therapeutic and diagnostic purposes. Unique electrical and optical properties of gold NP known as surface plasmon resonance assist medical diagnosis. In this work we look at the basic methods for gold NP synthesis and modification, including the so-called green chemistry, talk about the pharmacological aspects of their application and highlight their potential as diagnostic agents. We believe that due to their unique properties, gold-based nanoplatforms for targeted drug delivery and theranostics have indisputable advantages over other nanoparticles.

Received: 2018-11-29

Published online: 2018-12-31

DOI: 10.24075/brsmu.2018.090

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VIEWS 4788

Stukalov YuV, Grigorieva EYu, Smirnova AV, Lipengolts AA, Kubasova IYu, Pozdniakova NV, Lukashina MI

Radionuclide therapy (RNT) is an effective modality for treating multiple metastases in patients with cancer. The list of malignancies that can be managed with RNT expands with the arrival of novel tumoritropic radiopharmaceuticals (RP). A versatile delivery platform capable of carrying various therapeutic and diagnostic radionuclides, as well as vector molecules needed to achieve sufficient specificity to tumor cells and ensure therapeutic efficacy may hold great promise for radiation therapy. The aim of this work was to assess the performance of a delivery system based on the original dendrimer. The dendrimer demonstrated low toxicity in mice (LD50 was 779 ± 111 mg/kg). To study the specificity of the dendrimer to tumor cells and its therapeutic efficacy, we used a nanostructure (NS) composed of the dendrimer itself, the RGD peptide and 188Re (188Re-NS). Lewis lung carcinoma LLC1 was used as a tumor model. The biodistribution analysis revealed that the compound effectively accumulated in the tumor demonstrating a tumor-to-normal ratio >1 (relative to healthy organs and tissues) and retention time of at least 6 hours. Injections of 185 MBq/kg 188Re-NS caused a statistically significant inhibition of tumor growth (p < 0.05) by day 7 following the injection (Т/С = 5%), which remained stable for 6 days. Our findings suggest that the proposed dendrimer is a promising platform for RP delivery.

Received: 2018-09-12

Published online: 2018-12-31

DOI: 10.24075/brsmu.2018.089

Comments 0

VIEWS 4704