General dynamics of the URT microbiome and microbial signs of recovery in COVID-19 patients.

COVID-19 is caused by an airborne virus, SARS-CoV-2. The upper respiratory tract (URT) is, therefore, the first system to endure the attack. Inhabited by an assemblage of microbial communities, a healthy URT wards off the invasion. However, once invaded, it becomes destabilised, which could be crucial to the establishment and progression of the infection. We examined 696 URT samples collected from 285 COVID-19 patients at three time-points throughout their hospital stay and 100 URT samples from 100 healthy controls. We used 16S ribosomal RNA sequencing to evaluate the abundance of various bacterial taxa, α-diversity, and ß-diversity of the URT microbiome. Ordinary least squares regression was used to establish associations between the variables, with age, sex, and antibiotics as covariates. The URT microbiome in the COVID-19 patients was distinctively different from that of healthy controls. In COVID-19 patients, the abundance of 16 genera was significantly reduced. A total of 47 genera were specific to patients, whereas only 2 were unique to controls. The URT samples collected at admission differed more from the control than from the samples collected at later stages of treatment. The following four genera originally depleted in the patients grew significantly by the end of treatment: Fusobacterium, Haemophilus, Neisseria, and Stenotrophomonas. Our findings strongly suggest that SARS-CoV-2 caused significant changes in the URT microbiome, including the emergence of numerous atypical taxa. These findings may indicate increased instability of the URT microbiome in COVID-19 patients. In the course of the treatment, the microbial composition of the URT of COVID-19 patients tended toward that of controls. These microbial changes may be interpreted as markers of recovery.

[The clinical significance of the lamotrigine pharmacokinetic variability]. / Klinicheskoe znachenie farmakokineticheskoi variabel'nosti lamotridzhina.

AIM: To estimate pharmacokinetic variability of lamotrigine (LTG) and its clinical significance. MATERIAL AND METHODS: One hundred patients, including 74 women, aged from 18 to 77 years (38.23±14.37 years), with focal epilepsy were examined. Monotherapy with LTG was administered to 54 patients, duotherapy to 46 patients (LTG and valproic acid combination to 27 patients, LTG and liver enzymes inducers to 19 patients). Patients underwent procedures of therapeutic drug monitoring (TDM). Minimal (Cssmin) and maximal (Cssmax) steady-state LTG plasma concentrations, and concentration-to-weight ratio (CDR) were calculated. RESULTS AND CONCLUSION: In patients who used LTG in monotherapy, LTG Cssmin was 5.6±4.65 mg/l, Cssmax 7.59±5.54 mg/l. In the group that received LTG in combination with valproate, LTG Сssmin was 7.8 [5.4; 11.8] mg / l and Cssmax 11.4 [7.3; 15.3] mg/l. In the group that received LTG in combination with drug-inducers of glucuronidation, Cssmin was 2.5 [1.99; 4.32] mg/l, Cssmax 4.73 [2.91; 6.70] mg/l. Statistically significant differences in CDR parameter between groups with LTG monotherapy and duotherapy, both with inducer and with inhibitors, as well as between groups of duotherapy with inductors and with inhibitors were obtained. The results of the study indicate a pronounced pharmacokinetic variability of the LTG. Conducting TDM allows the establishment of individual therapeutic concentrations of LTG in blood plasma and setting a correction vector for antiepileptic therapy.

[Association of several polymorphic loci of serotoninergic genes with unipolar depression].

Serotoninergic system is one of the major brain neurotransmitter systems that is involved in the development of depression disorders. Regulatory genes of this system are the principle candidate genes predisposing to unipolar depression. Using PCR-RFLP analysis, we have conducted a study of polymorphic loci of several genes of this system: C1019G of serotonin receptor 1A gene, (HTR1A); A438G of serotonin receptor 2A gene, (HTR2A); G861C of serotonin receptor 1B gene, (HTR1B); Stin2VNTR and 5-HTTLPR of serotonin transporter gene (SLC6A4) in patients with unipolar depression among ethnic Tatars and Russians. The results of the study suggest that genotype 10/10 of the SLC6A4 gene as well as genotype G/G and allele G of the HTR2A gene can predispose for increased risk of unipolar depression development in ethnic Russians. In contrast, genotype 12/10 of the SLC6A4 gene is a marker of low risk of the disease development in both ethnic groups.