[Targeting NMDAR/AMPAR: a promising pharmacotherapeutic approach for depressive disorders]. / Targetirovanie NMDAR/AMPAR ­ perspektivnyi podkhod farmakokorrektsii depressivnykh rasstroistv.

Depression is a leading cause of disability and reduced work capacity worldwide. The monoamine theory of the pathogenesis of depression has remained dominant for many decades, however, drugs developed on its basis have limited efficacy. Exploring alternative mechanisms underlying this pathology could illuminate new avenues for pharmacological intervention. Targeting glutamatergic pathways in the CNS, particularly through modulation of NMDA and AMPA receptors, demonstrates promising results. This review presents some existing drugs with glutamatergic activity and novel developments based on it to enhance the efficacy of pharmacotherapy for depressive disorders.

[Determination of the presence of an antibiotic in implant-bone biopsy specimens by Raman spectroscopy in experiment]. / Opredelenie nalichiya antibiotika v implantato-kostnykh bioptatakh metodom ramanovskoi spektroskopii v eksperimente.

THE AIM OF THE STUDY: Was to determine the presence of an amoxicillin-based antibiotic in bone implant biopsies by Raman spectroscopy in an experiment. MATERIALS AND METHODS: Experimental animals (n=10, a miniature pig of the Svetlogorsk breed) were divided into 2 groups of 5 animals. Groups 1 and 2 were injected with amoxicillin 2 ml per 20 kg of body weight 30 minutes before dental implantation surgery, then group 2 was additionally injected with 1 ml per 20 kg of body weight for 5 days. Each animal has 6 implants installed. On the 1st, 3rd, 7th, 14th day, an implant-bone biopsy was removed from each animal, micro-preparations were made and Raman spectroscopy was performed to assess the peak matching of the Raman spectrum. RESULTS: In animals of the 1st and 2nd groups, the main peak of the Raman spectrum, which is closest to the values of the antibiotic spectrum of interest to us, is located closer to 1448 cm-1 and 1446 cm-1, respectively. At the same time, in both observations, the peaks relate to the spectrum of bone tissue, which cannot indicate the content of an antibiotic in the drug. CONCLUSION: No scattering spectra corresponding to the antibiotic molecule were found in any animal from both groups, regardless of the mode of administration and dosage of amoxicillin. The detected peaks corresponded to bone tissue without an antibiotic.

[Current status and prospects of using the prokinetic acotiamide in gastroenterology: A review].

Acotiamide is a prokinetic with a novel mechanism of action - an antagonist of muscarinic M1 and M2 receptors and an acetylcholinesterase inhibitor. Acetylcholine is the central mediator of the tone of the muscular components of the gastrointestinal tract, increasing its motor activity. Blockade of presynaptic M1 and M2 receptors neutralizes the inhibitory effect of the feedback mechanism on the acetylcholine synthesis, while inhibition of acetylcholinesterase in the synaptic cleft reduces the acetylcholine degradation. Currently, the clinical efficacy of acotiamide in the population of patients with functional dyspepsia is demonstrated in more than 10 clinical studies in different regions of the world, demonstrating a reduction of the symptoms of the disease during treatment with this agent and an improvement in the quality of life of patients. In addition, the combination of acotiamide with proton pump inhibitors optimizes the management of patients with gastroesophageal reflux disease.

Evaluation of Cellular Toxicity and Preclinical Safety of Using an Inhalable Liposomal form of Dexamethasone.

A liposomal form of dexamethasone was obtained. Liposomal vesicles were formed. The efficiency of incorporating dexamethasone into the liposomes was 99.7%. The cytotoxicity of the obtained liposomes was studied on a culture of human lung fibroblast cells using the MTT assay. The toxicity of liposomal dexamethasone was less than that of dexamethasone solution after a 24-h incubation. The half-maximum inhibitory concentration (IC50) was not achieved after 24 h when exposed to liposomal dexamethasone whereas IC50 was 27.5 mg/mL for lecithin (empty liposomes) and 177 µg/mL for dexamethasone solution. The toxicity of liposomal dexamethasone increased much more than that of dexamethasone solution after 48 h of incubation with IC50 values of 36 and 156 µg/mL, respectively. Thus, the liposomal form of dexamethasone has a latent period for implementation of the cytostatic (antiproliferative) action. Experiments on laboratory white rats of both sexes revealed that the inhalation use of liposomal dexamethasone insignificantly changed the functional parameters of their respiratory and cardiovascular systems. The study results could be used for conducting clinical trials.

[Study of the resistome of human microbial communities using a targeted panel of antibiotic resistance genes in COVID-19 patients].

AIM: To study overall drug resistance genes (resistome) in the human gut microbiome and the changes in these genes during COVID-19 in-hospital therapy. MATERIALS AND METHODS: A single-center retrospective cohort study was conducted. Only cases with laboratory-confirmed SARS-CoV-2 RNA using polymerase chain reaction in oro-/nasopharyngeal swab samples were subject to analysis. The patients with a documented history of or current comorbidities of the hepatobiliary system, malignant neoplasms of any localization, systemic and autoimmune diseases, as well as pregnant women were excluded. Feces were collected from all study subjects for subsequent metagenomic sequencing. The final cohort was divided into two groups depending on the disease severity: mild (group 1) and severe (group 2). Within group 2, five subgroups were formed, depending on the use of antibacterial drugs (ABD): group 2A (receiving ABD), group 2AC (receiving ABD before hospitalization), group 2AD (receiving ABD during hospitalization), group 2AE (receiving ABD during and before hospitalization), group 2B (not receiving ABD). RESULTS: The median number of antibiotic resistance (ABR) genes (cumulative at all time points) was significantly higher in the group of patients treated with ABD: 81.0 (95% CI 73.8-84.5) vs. 51.0 (95% CI 31.1-68.4). In the group of patients treated with ABD (2A), the average number of multidrug resistance genes (efflux systems) was significantly higher than in controls (group 2B): 47.0 (95% CI 46.0-51.2) vs. 21.5 (95% CI 7.0-43.9). Patients with severe coronavirus infection tended to have a higher median number of ABR genes but without statistical significance. Patients in the severe COVID-19 group who did not receive ABD before and during hospitalization also had more resistance genes than the patients in the comparison group. CONCLUSION: This study demonstrated that fewer ABR genes were identified in the group with a milder disease than in the group with a more severe disease associated with more ABR genes, with the following five being the most common: SULI, MSRC, ACRE, EFMA, SAT.

[Efficacy of Saccharomyces boulardii CNCM I-745 probiotic drug in the prevention and treatment of diarrhea in hospitalized patients with new coronavirus infection COVID-19].

AIM: To evaluate the efficacy of Saccharomyces boulardii (S. boulardii) CNCM I-745 probiotic drug in preventing and treating diarrhea in hospitalized patients with COVID-19. MATERIALS AND METHODS: A prospective comparative study was conducted in two parallel groups. The study included males and females aged 18 to 60 with the following diagnosis confirmed by polymerase chain reaction: U07.2 Coronavirus infection COVID-19, caused by SARS-CoV-2 virus (grade 1-3 pneumonia according to CT scan). All patients received antibiotic therapy. The patients were subdivided into two equal groups (n=60) depending on the administration of S. boulardii CNCM I-745 probiotic drug in addition to standard treatment. The probiotic was prescribed by the attending physician; the dose was 2 capsules per day (500 mg/day) 30 min before the meal for 10 days. All patients were monitored for main clinical, laboratory, and instrumental parameters during the study. In addition, the symptom of diarrhea (stool with a frequency of more than 3 times a day of type 6 and 7 according to the Bristol stool scale), including its frequency, duration, and the number of bowel movements of loose stool per day were precisely evaluated in both groups. RESULTS: In the overall patient pool, diarrhea was reported in 21.7% of in-patients during the observation period (95% confidence interval [CI] 14.2-29.1) with a mean duration of 4.6154 days (95% CI 3.7910-5.4398). The incidence of diarrhea in group 1 was 13.3% (95% CI 4.5-22.2), and in group 2, it was 30.0% (95% CI 18.1-41.9). Relative risk showed that the use of the S. boulardii CNCM I-745 probiotic drug leads to a significant reduction in the risk of diarrhea in hospitalized patients with COVID-19 infection receiving antibiotic therapy (odds ratio [OR] 0.3590, 95% CI 0.1421-0.9069; p=0.0303). In group 1, the duration of diarrhea was 3.1250 days (95% CI 2.5892-3.6608) versus 5.2778 days (95% CI 4.2290-6.3265) in group 2, p=0.0112. The mean daily frequency of loose stools in patients with diarrhea in group 1 was 3.2500 (95% CI 2.6588-3.8412) versus 4.3889 (95% CI 3.7252-5.0525) in group 2, p=0.0272. The secondary endpoint, duration of hospital stay, was also significantly shorter in group 1 patients - 11.6833 days (95% CI 11.2042-12.1625) versus 12.7333 days (95% CI 12.1357-13.3309) in group 2, p=0.0120. CONCLUSION: The present prospective comparative study demonstrated that adding S. boulardii CNCM I-745 probiotic drug into the standard treatment regimen of patients with new coronavirus infection COVID-19 receiving antibiotic therapy helps reduce the incidence of diarrhea and its severity during hospitalization, as well as the duration of hospital stay.

[Composition of oropharyngeal microbiota in patients with COVID-19 of different pneumonia severity].

AIM: To identify features of the taxonomic composition of the oropharyngeal microbiota of COVID-19 patients with different disease severity. MATERIALS AND METHODS: The study group included 156 patients hospitalized with confirmed diagnosis of COVID-19 in the clinical medical center of Yevdokimov Moscow State University of Medicine and Dentistry between April and June 2021. There were 77 patients with mild pneumonia according to CT (CT1) and 79 patients with moderate to severe pneumonia (CT2 and CT3). Oropharyngeal swabs were taken when the patient was admitted to the hospital. Total DNA was isolated from the samples, then V3V4 regions of the 16s rRNA gene were amplified, followed by sequencing using Illumina HiSeq 2500 platform. DADA2 algorithm was used to obtain amplicon sequence variants (ASV). RESULTS: When comparing the microbial composition of the oropharynx of the patients with different forms of pneumonia, we have identified ASVs associated with the development of both mild and severe pneumonia outside hospital treatment. Based on the results obtained, ASVs associated with a lower degree of lung damage belong predominantly to the class of Gram-negative Firmicutes (Negativicutes), to various classes of Proteobacteria, as well as to the order Fusobacteria. In turn, ASVs associated with a greater degree of lung damage belong predominantly to Gram-positive classes of Firmicutes Bacilli and Clostridia. While being hospitalized, patients with severe pneumonia demonstrated negative disease dynamics during treatment significantly more often. CONCLUSION: We have observed differences in the taxonomic composition of the oropharyngeal microbiota in patients with different forms of pneumonia developed outside hospital treatment against COVID-19. Such differences might be due to the presumed barrier function of the oropharyngeal microbiota, which reduces the risk of virus titer increase.