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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Antonova NP, Balabanyan VYu, Tkachuk AP, Makarov VV, Gushchin VA

One of the most promising approaches to combatting multiple drug resistance is based on the use of recombinant endolysins. In this work we study physical, chemical and lytic properties of phage KPP10, a recombinant endolysin effective against Pseudomonas aeruginosa at concentrations of 3 μg/ml. Fused with a fragment of positively charged SMAP-29 peptide into one reading frame, artilysin KPP10 is effective against laboratory strains and clinical isolates of Pseudomonas aeruginosa in the absence of permeabilizers. Our findings encourage preclinical trials of this artilysin in infectious models

Received: 2018-02-02

Published online: 2018-04-27

DOI: 10.24075/brsmu.2018.010

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VIEWS 4253

Amelina SS, Degtereva EV, Petrova NV, Marakhonov AV, Temnikov VE, Petrina NE, Amelina MA, Vetrova NV, Ponomareva TI, Zinchenko RA

Ichthyosis vulgaris (IV), a serious skin condition that runs in families, is actively studied worldwide. In this work we aimed to evaluate the prevalence of IV and frequency of two FLG mutations R501X and 2282del4 in the population of the Rostov region. Our genetic epidemiology study of hereditary monogenic disorders covered a total of 497,460 residents of 12 districts to identify 230 separate nosological entities. In the course of the analysis, we calculated the prevalence of IV per district and in the entire region and compared our findings with the results of earlier studies. The average prevalence of IV in the Rostov region was 1:5,025, which is consistent with the average prevalence of the disease across Russia (1:5,151). Tselinsky and Millerovsky districts demonstrated the highest prevalence rates (1:1,942 and 1:2,032, respectively). To evaluate the frequency of two FLG mutations R501X and 2282del4, we assayed the samples of 58 patients with IV and 127 healthy unelated controls by PCR followed by the restriction fragment length polymorphism analysis. In patients with IV, the frequency of the 2282del4 mutation was 48.28%, which is in line with European figures and also 30 times higher than in the controls (1.58%), suggesting the pathogenicity of the mutation. The R501X mutation was not identified both in patients with IV and healthy controls.

Received: 2017-11-17

Published online: 2018-04-16

DOI: 10.24075/brsmu.2018.009

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VIEWS 3540

Topchieva LV, Kurbatova IV, Dudaniva OP, Shipovskaya AA

Poor diet, sedentary behavior and genetic background are major factors contributing to the etiology and pathogenesis of non-alcoholic fatty liver disease (NAFLD). It is hypothesized that polymorphisms of the TNFRI and TNFRII genes coding for the receptors that bind the proinflammatory cytokine tumor necrosis factor alpha (TNFα) can be implicated in the susceptibility to NAFLD, but not much data is available in the literature. In the present work we aimed to investigate a possible association between the rs767455 T>C TNFRSF1A and rs1061622 T>G TNFRSF1B polymorphisms and one of NAFLD forms, nonalcoholic steatohepatitis (NASH), and to assess their effect on blood biochemistry. Samples of DNA isolated from the venous blood of 151 healthy donors and 242 patients with NASH were genotyped using PCR-RFLP. TNFα concentrations were measured by ELISA. We have not found any association between the rs767455 T>C TNFRSF1A polymorphism and the development of NASH in the residents of Karelia. However, we have discovered an association between NASH and the T>G TNFRSF1B rs1061622 polymorphism. Carriers of the G allele have a higher risk of developing NASH (OR = 4.83; 95% CI: 2.72–8.57). The rs1061622 T>G genotype of the TNFRSF1B gene appears to have no effect on TNFα concentrations and the activity of alanineaminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Our findings suggest a possible association between the rs1061622 T>G TNFRSF1B polymorphism and a risk of developing NASH in the residents of Karelia.

Received: 2017-10-31

Published online: 2018-04-15

DOI: 10.24075/brsmu.2018.008

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VIEWS 3799

Kopetskiy IS, Eremin DA, Polunina NV, Polunin VS, Buslaeva GN, Khetagurova AK

Mandibular fractures are a common type of injuries of the facial bones. Most of them affect the angle and body of the mandible in the areas innervated by the inferior alveolar nerve (IAN). Inpatients of maxillofacial units often lack health literacy; therefore, the aim of our study was to improve the effect of treatment in patients with mandibular fractures and IAN injuries by motivating patients toward a healthy lifestyle and by pioneering the use of therapeutic agents Mexicor and Combilipen in the standard regimen.

Received: 2017-11-17

Published online: 2018-04-14

DOI: 10.24075/brsmu.2018.007

Comments 0

VIEWS 3484

Udzhukhu VYu, Sharova NM, Korotkiy NG, Davtyan EV, Kukalo SV

Being a relatively common chronic skin condition with understudied pathogenesis, nummular eczema captures attention of medical researchers. The aim of this wok was to describe clinical manifestations of the disease, revise criteria for its accurate diagnosis and understand the role of malfunctioning components of the adaptive and innate immunities in triggering the inflammatory response. Using high-sensitivity ELISA assays, we assessed the cytokine profiles, determined the levels of adhesion molecules and the affinity of serum antibodies in 51 patients with nummular eczema. The immune profiles of the patients were dominated by proinflammatory interleukins, being deficient in regulatory cytokines. The relative abundance of mononuclear CD50+ and CD54+ cells was increased. Natural antibacterial immunity was weakened by the production of lowaffinity serum antibodies. Based on our findings, we have established criteria for the differential diagnosis of nummular eczema and described a contribution of both regulatory and effector immunity components to the abnormal immune homeostasis. We conclude that the discovered defects of the humoral regulation and non-specific resistance in patients with nummular eczema are pathogenic and determine the course of the disease.

Received: 2018-02-05

Published online: 2018-04-12

DOI: 10.24075/brsmu.2018.006

Comments 0

VIEWS 3313

Bilan DS, Shokhina AG, Panova AS, Belousov VV

The zebrafish Danio rerio is a popular model species for biomedical research focusing on modeling human diseases and screening of therapeutic drugs. Genetically encoded biosensors based on fluorescent proteins are widely used in many laboratories worldwide to study the biology of living systems of various complexity in vivo. The main advantage of these molecular tools is that they allow observing biological processes in intact systems in real time. In the present work we study the dynamics of the intracellular ratio of NAD+ to NADP in the yolk sac and tissues of D. rerio larvae using the SoNar biosensor following the injection of glycolisis end products, lactate and pyruvate.

Received: 2017-12-05

Published online: 2018-03-14

DOI: 10.24075/brsmu.2018.005

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VIEWS 4306

Osipova ZM, Shcheglov AS, Yampolsky IV

Bioluminescence is chemical oxidation of a small luciferin molecule by air catalyzed by luciferase and accompanied by the emission of photons in the visible spectrum. This reaction is used in bioluminescent bioimaging, the method for the visualization of organism’s interior. Bioimaging is a popular tool used in medical research. However, it has an unfortunate drawback: it requires introduction of external luciferin to the system before every experiment. In this work we discuss a possibility of developing an autonomous luminescent system in eukaryotes based on the bioluminescent system of higher fungi.

Received: 2017-12-15

Published online: 2018-03-05

DOI: 10.24075/brsmu.2018.004

Comments 0

VIEWS 3862

Pinto TCA, Banerjee A, Nazarov PA

There is an urgent need for new antimicrobial and therapeutic strategies to deal with the ever evolving antimicrobial resistance among the most prevalent bacterial pathogens. Infections due to virulent bacteria remain significant causes of morbidity and mortality despite progress in antimicrobial therapy, primarily because of the increasing of antimicrobial resistance levels among such group of bacteria. Despite significant advances in the understanding of the pathogenesis of infection due to these organisms, there are only limited strategies to prevent infection. Recently it was reported that SkQ1, triphenyl phosphonium-based mitochondria-targeted antioxidant and antibiotic, effectively kills all tested Gram-positive laboratory strains including of Bacillus subtilis, Staphylococcus aureus and Mycobacterium sp. Moreover, SkQ1 demonstrated effectiveness towards Gram-negative strains too, except Escherichia coli. The mechanism of the bactericidal action of TPP-based antibiotics could be also described by its ability to suppress bacterial bioenergetics by collapsing membrane potential through activation of protonophorous uncoupling. To this date, there are no reports of resistance to SkQ1 among Gram-positive strains; therefore, triphenyl phosphonium-based antibacterial agents would be effective towards planktonic and sessile cells of clinical resistant strains.

Received: 2018-01-23

Published online: 2018-03-05

DOI: 10.24075/brsmu.2018.003

Comments 0

VIEWS 4546