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Antibiot Khimioter = Antibiotics and Chemotherapy

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Vol 66, No 5-6 (2021)
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EXPERIMENTAL STUDIES

4-10 2050
Abstract

Introduction. The COVID-19 pandemic has stimulated the search for drugs with specific antiviral activity against the new pathogenic strain of the SARS-CoV-2 coronavirus. First of all, scientific search was aimed at studying drugs with already proven efficacy against influenza and ARVI. The aim of this work was to study the antiviral activity of Cytovir®-3 in vitro in relation to the cytopathogenic effect of the SARS-CoV-2 virus. Material and methods. The antiviral activity of the drug Cytovir®-3 against the SARS-CoV-2 virus was studied in experimental models in vitro on Vero CCL81 cell culture (ATCC). The maximum tolerated concentration and the 50% cytotoxic dose were determined using a quantitative microculture tetrazolium test assay to calculate the working range of the concentrations of the test drug. Results and discussion. As a result of the study, it was shown that the greatest activity of the drug was manifested when it was added to the cells 24 hours before and 1 hour and 24 hours after viral infection, the inhibition level reached 53% (>IC50) at the drug concentrations of 105, 55, and 85 µg/ml, respectively. Cytovir®-3 suppressed the viral activity of SARS-CoV-2 in the dose range from 10 µg/ml to 105 µg/ml under the indicated infection conditions. It was found that the drug did not exhibit cytotoxic effects on the Vero cell culture in the range of antiviral doses. Conclusion. The antiviral activity of Cytovir®-3 against the SARS-CoV-2 virus has been proven due to the achievement of IC50, which is below the maximum tolerated dose of 149 µg/ml.

11-16 3360
Abstract

On account of the COVID-19 pandemic, the global pharmaceutical industry has achieved impressive results in the development and introduction of various types of vaccines causing the formation of acquired immunity against the SARS-CoV-2 coronavirus into clinical practice. However, none of them currently show the declared one hundred percent guarantee of protection. In the case of the COVID-19 disease, patients with concomitant pathologies are the most vulnerable to the occurrence of severe complications. The aerosol route of transmission of SARS-CoV-2 contributes to the emergence of outbreaks of the new coronavirus infection in crowded places and closed rooms with poor ventilation. In this regard, an urgent problem is the search for drugs with local antiviral activity, which, together with restrictive measures and mask wearing policy, can potentially reduce the likelihood of contracting coronavirus. In this experimental in vitro study on Vero CCL81 cell culture (ATCC), the local antiviral activity of the drug Thymogen® spray against the SARS-CoV-2 virus was studied in comparison with the antiseptic Miramistin® solution. As a result of the experiment, no toxic effects on Vero cells were detected in the drugs in the studied concentrations. In a series of experiments, Thymogen® spray showed local antiviral activity against SARS-CoV-2 when the virus titer was 5,2 lg TCID50. Therefore, the drug Thymogen® dosed nasal spray has high potential as a topical drug for prevention and treatment of COVID-19 disease, which requires additional confirmation in relevant clinical studies.

17-22 903
Abstract

Aim. To assess the mechanisms of immunoadjuvant activity of marine bacteria exopolysaccharides (PS) in normal and immunosuppressive conditions in vivo. Material and methods. Experimental studies were carried out on male ВALB/c mice, immunized with compositions of PS or aluminum hydroxide and ovalbumin (OVA). Immunosuppression was induced by triple intraperitoneal administration of dexamethasone (2 mg/kg). Serum levels of specific antibodies (IgG, IgG1, and IgG2a) and cytokines (IFN-γ, IL-2, IL-10) were determined. Results. The inclusion of PS to the immune compositions led to the formation of an enhanced specific IgG, IgG1, and IgG2a to OVA, comparable to the effect of aluminum hydroxide. The studied PS also contributed to an increase in the level of both pro- and anti-inflammatory cytokines. Conclusion. PS from marine bacteria act as adjuvants in normal and immunosuppressive conditions, stimulating a mixed Th1 (IgG2a, INF-γ) and Th2 (IgG1, IL-10) immune response to OVA.

GUIDELINES FOR PRACTITIONERS

23-29 673
Abstract

The expression level of estrogen receptors (ERα and ERβ) in surgical tumor biopsy specimens from 167 patients with non-small cell lung cancer (NSCLC) was quantified by flow cytometry-based immunofluorescence analysis. ERα and ERβ expression was revealed in all the tumor samples investigated. The level of ERα expression in the tumors varied from 10 to 58% and ERβ — 12% to 80%, indicating significant heterogeneity of estrogen receptor expression in tumors of different patients. The mean ERβ expression level was approximately 2-times higher compared to ERα (42.1±15.3% vs 21.4±11.3%; p<0.001). It allows to consider ER>β as a major estrogen target in NSCLC tissue. The level of ERα and ERβ expression in NSCLC tissue is independent of gender, smoking status, and the histological type of the tumor. Increased ERβ expression was detected only in male patients with lung adenocarcinoma in comparison with squamous cell carcinoma (p=0.02). The assessment of the correlation between ERα and ERβ in both the whole cohort of patients and subgroups with clinically relevant disease parameters revealed that the level of one marker does not predict the other one’s expression. The coefficient of determination, which characterizes how differences in one variable can be explained by the difference in a second variable, was less than 25% in any comparison group. The authors consider that the high level of ERβ expression and ERα coexpression in NSCLC tissue substantiates the clinical perceptiveness of a new treatment option for the disease, namely, adjuvant hormone (antiestrogen) therapy.

30-34 500
Abstract

The problem of infectious endocarditis currently deserves special attention. According to the data, intrahospital mortality caused by this pathology reaches 20%, which is largely due to the development of potential complications, the most common among which are the development and progression of heart failure, as well as thromboembolic manifestations with the damage to target organs of various localization. The article presents the results of a multicenter study establishing the features of antimicrobial therapy in patients with infectious endocarditis under the conditions of the dominance of gram-positive microorganisms in the etiological structure in the Russian Federation. 440 cases of definite and probable infectious endocarditis in the period from September 2006 to December 2020 were analyzed.

35-39 564
Abstract

The study of the concentration of the main pro-inflammatory cytokines (IL-1β, IL-6 and TNF) in the blood serum of 48 patients with recurrent chronic herpesvirus infection was carried out. A significant increase of cytokine levels with the maximum values during the height of the disease was established. During the period of clinical symptoms’ subsidence, a decrease in their concentration with incomplete normalization is observed during the period of convalescence. Changes in the level of IL-1β, IL-6 and TNF in the blood serum of patients with recurrent herpesvirus infection depended on the period of the disease and the severity of the pathological process.

40-47 505
Abstract

The aim of the study was to evaluate the effectiveness of psychological (adherence to treatment) and accompanying drug therapy depending on the form of pulmonary tuberculosis. The results of complex therapy of 326 patients with various forms of pulmonary tuberculosis are considered. All patients received etiotropic treatment, taking into account the sensitivity of the pathogen to anti-tuberculosis drugs, as well as support therapy, including psychological support and, if indicated, hepatoprotective therapy with Remaxol. When analyzing the dependence of the psychoemotional state of patients on the form of the tuberculous process in the lungs, it was noted that high adherence to therapy was observed in one third of patients in all groups (DTL — 26.1%, ITL — 28.6%, FCTL — 32.8% and ATL — 31.8%, respectively, P>0.05). The results obtained may be associated with a high level of resistance of mycobacterium tuberculosis excreted from pa tients: out of 232 patients with low adherence to treatment (NUP and UUP), 97 (36.2%) showed drug resistance of the pathogen to two or more etiotropic drugs, which, in turn, caused prescription of reserve drugs. Thus, the determination of the level of adherence to treatment is justified and is aimed at correcting the psychological support of patients with pulmonary tuberculosis, which makes it possible to increase the effectiveness of therapy in these patients. The appointment of the latter in a number of patients led to the development of hepatotoxic reactions, which served as the basis for the inclusion in the therapy regimens of the accompaniment of Remaxol (intravenous drip of 400 ml, course No. 5–7). Pronounced hepatoprotective (improved transaminase parameters) and insignificant immunoprotective (positive dynamics of the cytokine profile) effects were noted during treatment. The noted changes in the immunogram can be associated with the proven antioxidant and membrane stabilizing effect of succinic acid, which is part of Remaxol. These changes require further research.

48-57 1066
Abstract

The aim of the study was to carry out meta-analysis of randomized controlled trials in order to combine the results of clinical trials on Triazavirin® (Riamilovir) efficacy in the etiotropic therapy of acute respiratory viral infection. Materials and methods. The studies included 435 patients with a confirmed diagnosis of acute respiratory viral infection or ARVI (with laboratory confirmed absence of influenza virus antigens). The research was carried out in 27 centers. In studies, patients were divided into 3 groups in a 1:1:1 ratio (a total of 145 people per group). Each study included a group taking 100 mg of the medication 5 times a day, a group taking 250 mg of the medication 3 times a day and a placebo 2 times a day, as well as a group taking a placebo 5 times a day. The analysis was carried out in accordance with the PRISMA principles regarding the quality of information presentation on the results of systematic reviews and meta-analyzes of works evaluating the effects of medical interventions. Results. The conducted meta-analysis showed that the use of Triazavirin® (Riamilovir) has a statistically significantly effects on the severity of clinical symptoms in patients with ARVI. The performed meta-analysis confirmed reliable associations between the use of Triazavirin® (Riamilovir) in both doses and the chance of a persistent improvement in clinical symptoms on the 5th day of therapy. The meta-analysis also confirmed the statistical significance of the clinical effects of Riamilovir by such indicators as the area under the curve «point on the scale showing the severity of the condition in a patient with ARVI in relation to time», the proportion of patients with complete alleviation of all symptoms by the end of the 5th day from the start of therapy. Conclusion. The clinical trials proved that the use of Triazavirin® (Riamilovir) is effective both in the initial and in the late stages of the disease, therefore, the drug can be used in the initial therapy of adult patients with respiratory diseases of viral etiology.

58-71 991
Abstract

The aim of the study was to carry out a meta-analysis of randomized clinical trials in order to combine the results of clinical trials on Triazavirin® (Riamilovir) efficacy in etiotropic therapy of influenza.

Materials and methods. The analysis was carried out in accordance with the PRISMA principles regarding the quality of information presentation on the results of systematic reviews and meta-analyzes of works assessing medical interventions. The study included 471 patients with a confirmed diagnosis of influenza (with laboratory confirmed presence of influenza virus antigens).

Results. The conducted meta-analysis showed that the use of Triazavirin® (Riamilovir) has a statistically significant effect on the severity of clinical symptoms in patients with influenza, therefore Riamilovir can be used in the initial therapy of adult patients with influenza.

Conclusion. Clinical studies have shown that the use of Triazavirin® (Riamilovir) is effective both in the initial and late stages of the disease, and therefore Riamilovir can be used in the treatment of adult patients with respiratory diseases of viral etiology, in particular, those diagnosed with influenza. The meta-analysis of the collected data showed that therapy with Triazavirin® (Riamilovir) has statistically significant advantages in various aspects both in comparison with the placebo group and with the Tamiflu® (Oseltamivir) group.

REVIEWS

72-77 761
Abstract

The study of microbial DNA from paleontological and archaeological samples is a powerful tool for estimating the molecular evolution of human pathogens. The paper is a retrospective review of the most significant achievements in medical paleomicrobiology. The subject of the discussion is the genetic diversity of ancient microbiomes including pathogenicity and antibiotic resistance genes. Paleomicrobiological studies of permafrost as a repository of pathogenic microbiota are highly promising.

78-85 997
Abstract

The review article presents an analysis of literature data on the necessity to expand the range of medications possessing anti-tuberculosis activity for the treatment of the most severe forms of drug-resistant tuberculosis through the use of beta-lactam antibiotics in chemotherapy regimens. The mechanism of action of beta- lactam antibiotics on mycobacterium tuberculosis is shown, and the results of in vitro studies to assess their anti-tuberculosis activity are presented. Clinical studies on the use of carbapenems prove the feasibility of their use for the treatment of patients with tuberculosis with multiple and extensive drug resistance of the pathogen.

135
Abstract

The study of microbial DNA from paleontological and archaeological samples is a powerful tool for estimating the molecular evolution of human pathogens.

The paper is a retrospective of the most significant achievements in medical paleomicrobiology. The subject of discussion is the genetic diversity of ancient microbiomes including pathogenicity and antibiotic resistance genes. Paleomicrobiological studies of permafrost as a repository of pathogenic microbiota are highly promising.

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ISSN 0235-2990 (Print)