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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Maslyakov VV, Krjukov EV, Barsukov VG, Kurkin KG, Dorzhiev PA, Gorbelik VR

Injuries to the heart are uncommon in peacetime, yet they result in life-threatening conditions, which makes timely diagnostics a crucial factor in saving patients' lives. In this connection, it is important to define the main signs of heart injuries. This study aimed to analyze the basic clinical symptoms associated with various wounds to the heart. We have retrospectively analyzed such symptoms registered in 86 patients with varying chest injuries that affect the heart. All patients were treated in the emergency surgery unit of the Engels Town Hospital from 1991 to 2017. 41 (47.6%) patient had stab wounds, and there were 45 (52.3%) cases of gunshot wounds. 23 (26.7%) patients had chest injuries affecting heart exclusively, while for 63 (73.2%) the consequences were wounds to other organs. We found that the clinical picture depends on the kind of injury to the heart: stab and slash wounds translate into more pronounced symptoms, while gunshot wounds do not produce such an effect. Accepting patients, practitioners should take this fact into account. The misdiagnosis rate for stab and slash heart wounds is 9.7%, that for gunshot wounds — 17.7%, the latter being the result of vagueness of the clinical picture. The clinical signs are most pronounced in the cases of stab and slash wounds to the heart.

Received: 2018-07-03

Published online: 2019-02-28

DOI: 10.24075/brsmu.2019.003

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VIEWS 3487

Kravchenko YuE, Ivanov SV, Kravchenko DS, Frolova EI, Chumakov SP

Selection of antibodies using phage display involves the preliminary cloning of the repertoire of sequences encoding antigen-binding domains into phagemid, which is considered the bottleneck of the method, limiting the resulting diversity of libraries and leading to the loss of poorly represented variants before the start of the selection procedure. Selection in cell-free conditions using a ribosomal display is devoid from this drawback, however is highly sensitive to PCR artifacts and the RNase contamination. The aim of the study was to test the efficiency of a combination of both methods, including pre-selection in a cell-free system to enrich the source library, followed by cloning and final selection using phage display. This approach may eliminate the shortcomings of each method and increase the efficiency of selection. For selection, alpaca VHH antibody sequences suitable for building an immune library were used due to the lack of VL domains. Analysis of immune libraries from the genes of the VH3, VHH3 and VH4 families showed that the VHH antibodies share in the VH3 and VH4 gene groups is insignificant, and selection from the combined library is less effective than from the VHH3 family of sequences. We found that the combination of ribosomal and phage displays leads to a higher enrichment of high-affinity fragments and avoids the loss of the original diversity during cloning. The combined method allowed us to obtain a greater number of different high-affinity sequences, and all the tested VHH fragments were able to specifically recognize the target, including the total protein extracts of cell cultures.

Received: 2018-12-08

Published online: 2019-02-25

DOI: 10.24075/brsmu.2019.002

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VIEWS 3632

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 3375

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 3757

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 3396

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 3536

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 3435

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

Comments 0

VIEWS 3589