Bulletin of Russian State Medical University

Multiple drug resistance of nosocomial bacterial strains provoked by the unwise and uncontrolled use of antibiotics in medicine and agriculture seriously threatens modern healthcare: minor and trivial infections are about to kill again. A solution may lie in the development of new alternatives to antibiotics. This review highlights the most interesting approaches to the development of antibacterial drugs focusing on the most promising ones, such as phage therapy and phage lytic enzymes (lysins).

Ключевые слова

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.

Ключевые слова

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.

Ключевые слова

Photodynamic therapy (PDT) is an alternative to conventional therapies of infections. It can kill drug-resistant bacteria without damaging host tissues. In the present work we use the multiresistant strain PA21 of Pseudomonas aeruginosa to model a wound infection in mice and study the effect of PTD mediated by aqueous solutions of the anionic photosensitizer merocyanine 540 (solubilized in water and in 0.25 M sodium chloride) on bacterial decontamination and wound healing. To assess a therapeutic effect of PDT, we monitored bacterial contamination of the wound, measured the wound size in two planes using a caliper and carried out a histopathological examination of infected tissue sections. Our study reveals that PDT mediated by MC540 in the sodium chloride solution can induce bacterial death, inhibit bacterial re-growth and accelerate wound healing.

Ключевые слова

Perioperative antimicrobial prophylaxis (PAP) involves administration of antimicrobial agents (AMA) to patients undergoing a surgical intervention and aims to reduce the risk of postoperative infectious complications, especially at surgical sites. In the present work we assess efficiency and safety of AMA used for prevention of postoperative infectious complications. In the course of our study we pre-analyzed 576 medical histories of post-op patients aged 18 to 87 years (mean age М ± SD was 57.4 ± 14.5 years), of which 347 (60.2%) were male and 229 (39.8%) female. Only 481 histories were selected for final analysis. We assessed the choice of antibacterial therapy, the frequency of adverse reactions (AR) and infectious complications and the type of the latter. PAP regimens were consistent with the official guidelines in 207 (43.04%) cases. PAP recommendations were ignored in 274 cases (56.96%), and the timing was wrong in 364 cases (75.7%). Incorrect dosages were administered in 225 cases (46.8%). We also discovered an association between irrational PAP regimens and 1) the length of patient’s stay in the intensive care unit (р = 0.003 and р < 0.005), 2) the frequency of reoperations associated with infection (р = 0.001), 3) mortality rates (р = 0.002), and 4) isolation of strains with multidrug resistance (р = 0.016). We conclude that PAP regimens for the inpatients of surgical wards are often compromised by failure to comply with the official guidelines, wrong timing and incorrect dosage, which negatively affects hospital statistics.

Ключевые слова

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 alanine aminotransferase (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.

Ключевые слова

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. Keywords: ichthyosis vulgaris, mutations R501X and 2282del4, FLG gene, prevalence rates, Rostov region

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.

Ключевые слова

A molecular marker for the risk of endometriosis recurrence can help to customize a post-operative treatment plan for an individual patient. The aim of this study was to compare the expression of genes coding for estradiol (mER, ERα, ERβ) and progesterone (PGRmC1, mPR, РR-А, PR-B) receptors in first-time and relapsing patients with ovarian endometriosis. Our study included 94 women of reproductive age with ovarian endometriosis: 82 first-time and 12 relapsing patients. The expression of genes coding for steroid receptors was measured using reverse transcription polymerase chain reaction. Recurrent conditions were characterized by a change in the expression of estrogen receptors and unchanged expression of progesterone receptors. Expression of mER in the tissue of patients with first-time endometriosis was 15.09 ± 1.18. Patients undergoing recurrence demonstrated a 3-fold increase in mER expression (from 15.09 ± 1.18 to 44.45 ± 9.1). Also, in such patients ERβ expression was 5 times higher increasing from 11.71 ± 0.22, which is an average value for first-time patients, to 10.02 ± 3.81, while ERα expression surged 7-fold from 10.47 ± 1.05 to 1.68 ± 0.55 (p < 0.05). Transcription of the studied receptors in the pathological tissue depended on the stage of the disease: in relapsing patients expression of estradiol receptors underwent some changes, while expression profile of progesterone receptors remained unchanged. Sensitivity of endometrial tissue to gestogens is clinically important and serves as a basis for a successful hormone-based relapse prevention.

Ключевые слова

Recent studies of T-cell clonal repertoires of patients with ankylosing spondylitis (AS) have led to the discovery of AS-associated T-cell clones with a highly homologous T-cell receptor structure. The role of T-lymphocytes in the disease progression cannot be elucidated without analyzing the diversity and abundance of functionally different T-cell clones found in patient with AS. Using a state-of-the-art technique for T-cell repertoire profiling based on massively parallel sequencing, we, for the first time, studied the T-cell repertoire of activated T-cells from the peripheral blood of a patient with AS. We have demonstrated that a subpopulation of CD38+HLA-DR+ T-lymphocytes is highly diverse both in terms of clonal diversity and abundance of the identified clonotypes, suggesting diverse antigen specificity of the activated peripheral blood T-cells. Most of the activated T-cell clonotypes had low abundance in total population of peripheral blood T-cells. In the repertoire of activated T-cells we have found the clonotype TRBV9_CASSVGVYSTDTQYF_TRBJ2-3, previously discovered in AS and reactive arthritis, and a few other clonotypes of cytotoxic and helper T-cells that may have a role in promoting inflammation in AS patients. Presence of the AS-associated clonotypes in activated T-cell subset suggests that the T-cells might play an active role in ongoing inflammation during the disease progression. This provides rationale for further research of their antigen specificity and role in triggering or maintaining AS.

Ключевые слова

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.

Ключевые слова

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.

Ключевые слова

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.

Ключевые слова

Dislocation of the lateral end of the clavicle (LEC) constitutes over 26% of all dislocations, 11% of sports injuries and over 10% of acute injuries to the shoulder girdle, ranking 3rd after elbow and wrist joints dislocations. The majority of surgical techniques used to repair fresh injuries to the acromioclavicular joint (ACJ) do not account for its anatomy and biomechanics, resulting in postoperative instability of the joint in both vertical and horizontal planes. The aim of this study was to propose a highly effective technique for the surgical treatment of acute injuries to ACJ ensuring a better recovery of its function. Below we present the results of 112 patients who underwent minimally invasive acromioclavicular joint reconstruction. The outcome was very good in 111 patients (99.1%). The proposed technique helps to avoid damage to the biomechanics of the joint and to fully restore its anatomy within short time.

Ключевые слова