ABSTRACT
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.
ABSTRACT
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.
