Influence of the NAT2 gene polymorphic markers on the effectiveness and safety of treatment in patients with newly diagnosed pulmonary tuberculosis based on peripheral red blood cell dynamics

Background. Individual sensitivity to isoniazid in tuberculosis patients is determined by the presence of N-acetyltransferase 2 (NAT2) enzyme gene allelic variants in genome. Evaluation of quantitative and qualitative alterations in peripheral blood can be used for diagnosis, disease severity estimation, or as a clue for estimation of anti-tuberculosis chemotherapy effectiveness and safety.Aim: Find associations between acetylation type and peripheral red blood cell (RBC) dynamics; determine the effect of NAT2 acetylation rate on the effectiveness and safety of treatment in patients with newly identified pulmonary tuberculosis (TB) residing in the Sakha Republic (Yakutia).Methods. This study included 146 patients with various clinical forms of newly diagnosed pulmonary TB. Oral isoniazid, rifampicin, pyrazinamide, and ethambutol were administered patients. Genotyping was performed via real time PCR.Results. Rapid and intermediate acetylators showed an increase in hemoglobin concentrations and RBC erythrocyte hemoglobin content by the end of chemotherapy (P<0.05). Incidence of anemia was lower in intermediate acetylators, compared to rapid or slow acetylators (P=0.013). Negative correlation was established between absolute RBC count and slow acetylation type (P=0.017). Patients with rapid acetylation type showed increased RBC distribution width indexes RDW-CV and RDW-SD (P<0.05).Conclusions. An adequate therapeutic effect was achieved with standard doses of anti-TB medications in patients with intermediate acetylation type. Rapid and slow acetylators required anti-TB medication dose correction. Genotyping for NAT2 gene in patients with pulmonary TB enables clinicians to choose the optimal dose of anti-TB medications, specifically, isoniazid dose.

Nonmedical correction of lipid metabolism disorders in patients with chronic cerebral ischemia

The authors evaluated the effectiveness of the isolated use of iodine-bromine baths and ozone therapy, as well as their complex application in the correction of lipid metabolism disorders in chronic cerebral ischemia. Statistical analysis of biochemical parameters after the treatment made it possible to come to the conclusion about the sufficient effectiveness and feasibility of using the proposed methods.

Combination of nanosomal form of doxorubicin, interferon alpha, and nitroglycerin in the threatment of 101.8 glioblastoma in Wistar rats

The search for effective approaches to the treatment of patients with glioblastoma is one of the difficult tasks of neurooncology; standard methods of therapy show limited results. Combined therapy, which includes different antitumor mechanisms, can increase its effectiveness. The combination of PLGA nanoform of doxorubicin (Dox-PLGA), antitumor cytokine — interferon alfa (IFN-α), and nitrogen oxide (NO) donor nitroglycerin (NG) was investigated in this work both in vitro (rat C6 glioma) and in vivo (rat 101.8 glioblastoma). MTT assay in the C6 cell line showed great cytotoxicity and antiproliferative effect of the combination of IFN-α with Dox-PLGA and NG. The lowest tumour cell survival was observed when using a high dose of IFN-α (10 ng/ml) in mono-mode. In the in vivo experiment, 32 female Wistar rats with 101.8 glioblastoma received therapy in the following modes: Dox-PLGA + NG; Dox-PLGA + IFN-α; Dox- PLGA + IFN-α + NG. There was a significant increase in median survival and life expectancy (ILE) in all groups receiving therapy compared to the group that did not undergo treatment. The longest median lifespan (27 days), survival up to 100 days (1 animal), ILE (131%) were observed in animals that received the combination Dox-PLGA + IFN-α+ NG, compared to the group without treatment, in which the median lifespan was 15 days. Thus, the therapy of experimental glioblastoma both in vivo and in vitro with the combination of Dox-PLGA + IFN-α + NG has the most pronounced therapeutic and antitumor effect, which must be taken into account when developing new more effective methods of treating human glioblastomas.

Isolation of rare Genera of actinomycetes — antibiotic producers from soils using Aloe Arborescens juice

The search for new antibiotics is an urgent problem due to the spread of resistance to existing antibacterial drugs in pathogenic microorganisms. Actinomycetes are producers of a large number of antibiotics used in medicine. Most antibiotics are isolated from actinomycetes of the Streptomyces genus, while rare genera of actinomycetes can be the producers of new antibiotics.The aim of the study is to investigate the effect of the biological substances complex present in aloe juice on the growth stimulation of rare genera of actinomycetes.Material and methods. Objects: samples of sod-podzolic soil and chernozem. The standard method of sowing soil suspensions on oat agar and Gause medium No. 2 was used to isolate actinomycetes. Chemotaxonomic properties were determined using the methods of ascending thin-layer chromatography on a cellulose layer. The generic identity of cultures was determined using Bergey’s manual and materials comparing the composition of cell walls of actinobacteria. DNA PCR with standard 27f and 1492r primers, as well as Sanger sequencing, were performed to study genosystematic features. Antibiotic activity was determined against the test microorganisms: Staphylococcus aureus ИНА 00985 (FDA 209P), Staphylococcus aureus ИНА 00761 (MRSA), Staphylococcus aureus ИНА 00762 (УФ- 2), Micrococcus luteus ATCC 9341, Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Saccharomyces cerevisiae ИНА 01042.Results. A total of 527 actinomycete cultures were isolated from samples of sod-podzolic soil and chernozem with the addition of aloe juice; their phylogenetic position was determined. The dominant actinomycetes in the studied soil samples are the representatives of the genus Streptomyces. Bacteria of the genus Micromonospora take the second place by the number of isolated cultures. Rare genera of actinomycetes have also been identified: Nonomuraea, Streptosporangium, Nocardia, Actinomadura, Actinocorallia, Pseudonocardia, Amycolatopsis, Saccharomonospora, Saccharopolyspora, Promicromonospora, Kribbella. It was determined that the isolated cultures possess antibiotic activity against test microorganisms.Conclusion. It is advisable to use aloe juice after subjecting the leaves to biostimulation to isolate actinomycetes from the soil and identify their biodiversity.

Antimicrobial Resistance in Enterococci

Background. Enterococcus spp. are opportunistic agents of community-acquired and in-hospital infections, which have been considered a threat to public health due to their antimicrobial resistance, primarily to glycopeptides, in recent years.The aim of the study is to determine the prevalence of various Enterococcus species causing infections in hospitalized patients and their antimicrobial resistance.Methods included identification by MALDI-TOF mass spectrometry and antimicrobial susceptibility testing in accordance with the EUCAST or, in their absence, CLSI guidelines.Results. Antimicrobial resistance in 1562 consecutive Enterococcus strains isolated from hospitalized patients was determined in a major medical center admitting patients from various regions of the Russian Federation in 2019. The predominance of E.faecalis and E.faecium (99.5%) was revealed; the frequency of isolation of the former was 56% higher than that of the latter. E.avium, E.casseliflavus, E.gallinarum, E.durans were isolated from 0.5% of biological samples. The highest level of resistance of enterococci was observed to erythromycin (84.8%), tetracycline (75.0%), and rifampicin (68.2%). Multidrug, as well as vancomycin resistance, prevailed in E.faecium. All E.faecium strains isolated from blood were multidrug resistant. Resistance to vancomycin in enterococci, causing bloodstream infections, was observed solely in 19.5% of E.faecium; all vancomycin-resistant isolates were also resistant to teicoplanin. Linezolid resistance was detected in 2 community-acquired strains of E.faecalis (0.1%). Rare enterococci have shown diverse patterns of antimicrobial resistance.Conclusions. E.faecalis and E.faecium prevailed among Enterococcus spp. causing infections in hospitalized patients. Multidrug resistance and vancomycin resistance were observed predominantly in E.faecium, especially in strains causing blood-stream infections. Further monitoring of the spread and antimicrobial resistance of various Enterococcus spp. in hospital and community-acquired infections is needed.

Lyme disease: modern approaches to treatment and prevention (based on international recommendations of 2020)

Lyme disease (LD) or tick-borne borreliosis affects thousands of people every year in different regions of the world, primarily in the United States and Europe. Given the great social and medical importance of this problem, an updated version of the clinical guidelines for the prevention, diagnosis and treatment of PD was published in November 2020 by a committee of experts of the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN) and the American College of Rheumatology (ACR). This article discusses the main issues of the use of antibacterial drugs in LD. The most commonly used medications are doxycycline, amoxicillin, cefuroxime axetil, and ceftriaxone. Patients with erythema migrans receive appropriate antibiotics for 7–14 days, depending on the medication used. In case of other clinical manifestations of LD, the duration of treatment is extended to 14–28 days. Antibiotic prophylaxis is carried out using a single oral dose of 200 mg doxycycline for adults and 4.4 mg/kg (with a maximum of 200 mg) for children. This treatment scheme is highly efficient, easy to administer, and has a relatively low risk of adverse events.

A new generation of probiotics — psychobiotics, their purpose and functions

A review of the literature on the etiological role of the microbiome in the treatment of depressive disorders is presented based on an analysis of 98 literature sources for 2000–2020, of which 35 are domestic and 63 are foreign. Evidence is substantiated that the gut microbiome may represent a new potential target of antidepressant therapy. The emergence of a new class of probiotics (psychobiotics), as well as possible psychobiotic treatments, could be a promising strategy for improving the quality of life of people suffering from neurodegenerative diseases and developmental disorders of the nervous system.

Meta-analytical evaluation of the clinical efficacy of a complex metabolic neuroprotector in patients with chronic cerebral ischemia

The aim of the study is to evaluate the clinical efficacy, safety, and impact of the complex metabolic neuroprotector on the patients’ quality of life (CMN) Cytoflavin in tablets, as well as in the course of stepwise pharmacotherapy of patients with chronic cerebral ischemia (CCI) of various etiologies, followed by meta-analysis, on the basis of a systematic review of published clinical studies.Material and methods. A selection of randomized controlled trials was carried out over the past 15 years, in which CMN Cytoflavin was used in the tablet dosage form or in a stepwise course of therapy in at least 25 patients diagnosed with chronic cerebral ischemia with a total course of therapy of at least 25 days. The assessment of CMP clinical efficacy and the analysis of formalized indicators of clinical efficacy (relative risk, odds ratio, frequency of outcomes, values of absolute and relative benefits, etc.) was carried out.Results and conclusion. 403 publications for 2000–2017 describing the use of CMN Cytoflavin were analyzed. 16 studies were selected for the systematic review, the meta-analysis included 6 randomized clinical trials and one non-randomized study of the use of CMN in patients with CCI. The data of the systematic review and meta-analysis showed a sufficient efficacy of complex metabolic neuroprotector use in patients with chronic cerebral ischemia. However, the meta-analysis revealed significant heterogeneity between the studies. The drug has a beneficial effect on the quality of life of patients, increases the likelihood of a positive outcome in relation to the relief of asthenic and vestibular-atactic syndromes, in relation to complaints of increased fatigue, headache, dizziness, noise in the head, impaired coordination. It improves cognitive functions, exhibits sufficiently high tolerance and safety.

Genetic differences between Helicobacter pylori strains isolated from patients with chronic mild and severe gastritis

Background. Helicobacter pylori-associated chronic gastritis (CG), being a very heterogeneous group, still does not have a divisin based on Helicobacter pylori (Hp) genotyping data, which could predict the clinical form of CG.The aim of the study is to search for the prevalence of the cagA gene or any allelic combination of the vacA gene, or stable combinations of cagA and any allelic combination of vacA genes in Hp isolates from patients with mild and severe CG, as well as patients with peptic ulcer disease (PUD).Methods. Hp isolates from gastrobiopsy specimens were genotyped for cagA and vacA allelic combinations (s1m1, s2m1, s1m2, s2m2). The difference in the occurrence of vacA allelic combinations was assessed by Mann–Whitney U test; the conjunction of cagA and vacA allelic combinations was assessed by the Spearman's rank correlation coefficient (rs).Results. The cagA gene was found in more than half of all cases, both in patients with ulcer and in patients with CG (mild and severe). The incidence of vacAs1m1 (the most virulent allelic combination) showed no significant differences in all forms of gastritis and in PUD; the correlation between cagA and vacAs1m1 was significant in all groups of patients, rs ranged from 0.57 to 0.72. In patients with mild CG, an abundance of non-virulent allelic combination vacAs2m2 was observed, which was significantly different from its occurrence both in patients with severe CG and in patients with ulcer; the joint occurrence of vacAs2m2 and cagA in patients with mild CG was chaotic (rs=-0.13; P=0.40).Conclusion. In mild CG, despite the absence of significant differences in cagA and vacAs1m1 (when compared with severe CG and ulcer disease), strains with a non-virulent allelic combination vacAs2m2 were significantly dominant; therefore, the detection of this particular allelic combination of vacA speaks in favor of a mild course of CG.

Effect of Differences in the CLSI and EUCAST Criteria on the Interpretation of Enterobacteriaceae Sensitivity to Carbapenems

Relevance: The two systems for determining the susceptibility of bacteria to antimicrobial drugs, CLSI and EUCAST, are recommended for use in the global system of epidemiological surveillance of antimicrobial resistance of the World Health Organization. However, they differ in the methodology of setting an antimicrobial susceptibility testing, threshold values of cut-off points, as well as interpretation of results. The true significance of methodological differences between these systems for global microbiological monitoring is unclear.The aim of the study was to evaluate the influence of differences in the cut-off points of CLSI and EUCAST on the interpretation of antimicrobial sensitivity of microorganisms to carbapenems in Saint Petersburg.Design: screening and comparative study.Materials and methods. Sensitivity to Meropenem was studied in Escherichia coli (n=2956), as well as Klebsiella pneumoniae (n=1189) for the period of 2011–2013 and 2016–2019, and interpreted according to the threshold values of the two guidelines (2020). Results. The weighted Kappa showed good agreement between the EUCAST vs CLSI standards for both E.coli (0.58; 95% CI 0.55–0.61) and K.pneumoniae (0.77; 0.73–0.81). Mcnemar's Chi-square test revealed differences between the two standards in assessing sensitivity to Meropenem of E.coli which were 5.31% (95% CI 5.06–5.31%, P<0.0001), and of K.pneumoniae — 3.95% (95% CI 3.36–3.95%, P<0.0001).Conclusion. The reliability of determining sensitivity bacteria to anti-microbial drugs has a significant impact on their rational use and the results of microbiological monitoring. The first priority is to develop national standards that take regional characteristics into account.