ABSTRACT
The antiviral activity of recombinant human IFN-lambda type 1 (IFNλ-1) against culture strain of SARS-CoV-2 virus was determined by infecting a highly sensitive VeroE6 coronavirus cell culture after preincubation test (the cell monolayer was incubated with 4-fold dilutions of IFNλ-1 in a concentration range of 0.16-42,500 ng/ml in a culture medium for 12 h at 37°C) and without preincubation (simultaneous addition of different concentrations of IFNλ-1 and SARS-CoV-2 infection in a dose of 102 TCID50). The created recombinant human IFNλ-1 demonstrated obvious antiviral activity against SARS-CoV-2 virus in vitro. In the tests with and without preincubation, IFNλ-1 exhibited significant activity, although somewhat lower in variant with simultaneous addition of IFNλ-1 and virus to the cell culture. It should be noted that the antiviral effect of IFNλ-1 was observed in a wide range of concentrations.
Subject(s)
Antiviral Agents/pharmacology , Interferons/pharmacology , Recombinant Proteins/pharmacology , SARS-CoV-2/drug effects , Viral Load/drug effects , Virus Replication/drug effects , Animals , Antiviral Agents/isolation & purification , COVID-19/virology , Chlorocebus aethiops , Cloning, Molecular , Escherichia coli/genetics , Escherichia coli/metabolism , Gene Expression , Humans , Interferons/biosynthesis , Interferons/isolation & purification , Recombinant Proteins/biosynthesis , Recombinant Proteins/isolation & purification , SARS-CoV-2/genetics , SARS-CoV-2/growth & development , Vero Cells , Viral Load/genetics , COVID-19 Drug TreatmentABSTRACT
The use of lithium drugs in clinical practice requires constant monitoring of lithium plasma concentration, because toxicity is sometimes observed at therapeutic concentrations of lithium. This is often associated with fluctuations of plasma concentration of lithium ions after intake of individual doses. Therefore, the use of a porous carrier providing a stable blood level of the drug is extremely promising and important for clinical practice. We studied activity of a new lithium drug (lithium complex) consisting of aluminum-silicon base and lithium citrate immobilized on its surface. Lithium carbonate served as the reference drug. It was shown that lithium carbonate and lithium complex exhibited no anxiolytic activity in the conflict model, but produced an antidepressant effect and improved exploratory behavior of animals.
Subject(s)
Lithium/pharmacology , Silicones/chemistry , Aluminum Oxide/chemistry , Aluminum Oxide/pharmacology , Animals , Anti-Anxiety Agents/pharmacology , Exploratory Behavior/drug effects , Lithium Carbonate/chemistry , Lithium Carbonate/pharmacology , Male , MiceABSTRACT
The study examined the effects of a novel neurotropic medication based on a lithium complex composed of lithium citrate, polymethylsiloxane, and aluminum oxide on electrophysiological parameters of the rat brain. In contrast to lithium carbonate (the reference drug), the novel preparation resulted in a wave-like dynamics of electrical activity in the visual cortex. Rhythmic photic stimulation of the rats treated with lithium carbonate resulted in appearance of the signs attesting to up-regulation of excitability of cerebral cortex in all examined ranges. In contrast, the complex lithium preparation diminished the delta power spectrum, which was the only affected frequency band. It is hypothesized that the complex lithium medication induces milder activation of the cerebral cortex in comparison with lithium carbonate. The novel medication composed of lithium citrate, aluminum oxide, and polymethylsiloxane, is characterized by greater efficacy and safety than the preparation based on inorganic lithium salt (lithium carbonate).
Subject(s)
Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Lithium/pharmacology , Aluminum Oxide/pharmacology , Animals , Brain/drug effects , Brain/metabolism , Citrates/pharmacology , Electrophysiological Phenomena/drug effects , Lithium/chemistry , Lithium Carbonate/pharmacology , Male , Rats , Silicones/pharmacologyABSTRACT
The influence of a combination of ethinylestradiol (6.5 mg/kg) and gestodene (16.5 mg/kg) on the functional activity of P-glycoprotein efflux transporter and its expression in the liver and small intestine was studied on 20 Chinchilla rabbits. P-glycoprotein functional activity was characterized by the pharmacokinetics of its marker substrate - fexofenadine upon single peroral administration. P-glycoprotein expression was investigated by the immunohistochemical method. It was established that 14-day administration of ethinylestradiol - gestodene combination did not influence the functional activity of P-glycoprotein. After 21-day administration of this combination, the maximum concentration of fexofenadine and its area under concentration - time curve were increased and its clearance was decreased. These data are indicative of the inhibition of P-glycoprotein functional activity in the organism. Immunohistochemical analysis showed a reduction in the total expression of P-glycoprotein in the liver and small intestine after joint administration of ethinylestradiol and gestodene for 21 days, which confirmed a decrease in P-glycoprotein synthesis. Correlations between P-glycoprotein activity, its expression in the liver, and estradiol level were revealed.
