[Robot-assisted and robotic systems used in dentistry]. / Robot-assistirovannye i robotizirovannye sistemy, primeniaemye v stomatologii.

In the present study, the role of robot-assistance in dentistry and the main ways of its further development are analyzed. The basic structures of mechatronic devices and the features of their application in dentistry were reviewed. A retro-prospective analysis of the structures of robotic and robot-assisted systems used in dental practice was carried out. The development of robot-assisted and robotic systems should include the improvement of methods of intraoperative imaging, diagnostic tools, the improvement of surgical instruments, as well as the emergence of new robotic developments.

[Antiviral activity in vitro and pharmacokinetics of HCV entry inhibitor AVR560].

Several novel compounds were found to be potent inhibitors of the HCV (JFH-1 isolate) infection in vitro. Human serum did not significantly reduce antiviral activity of the lead compound, AVR560 (< 4-fold). The immunohistochemistry studies with the Huh7 cell line, infectable with the HCV (JFH-1 strain), demonstrated that AVR560 inhibited the early steps of viral infection and blocked the spread of the HCV infection in tissue culture. The cytotoxicity in Huh7 and Vero-76 cell lines was mild. AVR560 proved to be a specific HCV inhibitor and exhibited no activity against other flaviviruses such as yellow fever (strain 17D), West Nile (strain NY99), and dengue (New Guinea type 2) in in vitro infection experiments. AVR560 also did not inhibit any of the tested human CYP450 isozymes (3A4, 1A2, 2C19 and 2D6). In the pharmacokinetic studies in mice, rats and dogs, favorable pharmacokinetic profiles and good oral bioavailability were observed for AV560. Further pre-clinical studies with this novel HCV inhibitor are in progress.

[Preclinical study of AV0012 early stage inhibitor of hepatitis C virus infection: I. In vitro ADME and pharmacokinetics].

In vitro immunohistochemical investigations on the human hepatoma cell line (Huh7) infected with hepatitis C virus (HCV) strain JFH-1 showed that AV0012 compound blocks the early stages of viral infection. AV0012 also blocked viral infection spread in tissue culture through the secreted virus and through tight cell-to-cell contact. AV0012 is a specific inhibitor of HCV but not of related pestivirus, flaviviruses and other RNA-containing viruses such as bovine diarrhea (BVDV), Venezuelan equine encephalitis (strain TC-83), dengue type 2 (New Guinea), yellow fever (strain 17D), west Nile fever, parainfluenza (type 3) virus, RSV (strain A2), and Rhinovirus (type 2 strain HGP). It is established that human serum does not significantly affect the antiviral activity of AV0012 in vitro. The drug combination studies with AV0012 and interferon alpha 2a in vitro showed that the two inhibitors act additively, which makes possible the use of this combination in clinical tests. AV0012 is highly soluble and stable in aqueous solutions and murine blood plasma, has limited metabolic stability, low binding to human plasma proteins, high permeability through biological membranes, and only interacts with isoenzymes 2D6 and 3A4 of human cytochrome P450. In animal pharmacokinetic studies, AV0012 was rapidly absorbed into the blood stream upon oral administration, showed sufficiently long half-elimination times, and had high oral bioavailability that reached 92% in monkeys. Further preclinical development of AV0012 is in progress.

[Preclinical study of the new anti-influenza drug candidate AV0038 (ethyl 2-(dimethylaminomethyl)-5-hydroxy-1-methyl-6-(pyridin-3-yl)-1H-indole-3-carboxylate)].

In the framework of preclinical testing of AV0038, ethyl 2-(dimethylaminomethyl)-5-hydroxy-1-methyl-6-(pyridin-3-yl)-1H-indole-3-carboxylate, which showed high efficiency in the prevention and treatment of influenza A/Aichi/2/69 (H3N2) in mice, we have studied the drug solubility and stability in aqueous solutions, metabolic stability in human liver microsomes, stability in blood plasma of mice and humans, binding to plasma proteins of mice and humans, pharmacokinetics and bioavailability in mice, and the acute toxicity and the maximum tolerated dose. It is established that AV0038 has attractive pharmacological properties as anti-influenza drug candidate. The therapeutic doses of AV0038 do not cause acute toxicity in mice. It is expedient to continue preclinical investigations and study the drug metabolism, metabolites, and sub-chronic toxicity in test animals.

[Experimental rationale of hand stabilization devices use by teeth preparation].

This paper compares two methods of teeth preparation - with or without mechanical hand stabilization device preventing accidental angular deviations of dental handpiece during preparation. The results of two experiment series showed decreased convergence of side walls of the prepared teeth in cases when mechanical hand stabilizer corresponding to the values recommended in literature. It is concluded that mechanical hand stabilization device is a useful tool for improving the quality of preparations.

[Preclinical study of safety of the new pharmacological substance AV0012 to treat hepatitis C].

Pharmacological safety of a new type of HCV inhibitor, AV0012, was studied including acute, subchronic and chronic toxicity in mice, rats and monkeys. Genotoxicity was assessed using the Ames test and the chromosomal aberrations assay in the bone marrow cells of mice. It is established that AV0012 has low toxicity in SHK line mice, Wistar line rats, and monkey of Rhesus macaques species. Results obtained in the study of genetic toxicity showed that AV0012 exhibits no mutagenic activity. Data on general toxicity and mutagenicity discussed in this paper, together with data on 1 the pharmacological activity, pharmacokinetics, and metabolism published previously, allow us to consider AV0012 as a candidate drug for clinical research phase I.

[Toxicity of ethyl-3-(8-fluoro-2-methyl-2,3,4,5-tetrahydropyrido[4,3-b]indol-5-yl)-propionate dihydrochloride possessing antiallergic properties].

The toxicity of new gamma-carboline derivative [ethyl 3-(8-fluoro-2-methyl-2,3,4,5-tetrahydro-1H-gamma-carbolin-5-yl)-propionate dihydrochloride, CD-008-040] has been studied.

[Anti-allergic properties of a novel ethyl 3-(8-fluoro-2-methyl-2,3,4,5-tetrahydropyrido[4,3-b]indol-5-yl)propionate dihydrochloride].

The influence of ethyl-3-(8-fluoro-2-methyl-2,3,4,5-tetrahydro-1H-gamma-carboline-5-yl)propionate dihydrochloride belonging to the class of gamma-carbolines on the allergic reactions (inflammation and systemic anaphylaxis) has been studied on laboratory animals. It was established that the given substance administered in a dose of 5 - 20 mg/kg exhibits a pronounced antiallergic action. Unlike many other antihistamine drugs, this gamma-carboline derivative probably does not produce sedative effect.

[Substituted 2,3,4,5-tetrahydro-1H-gamma-carbolines: new antagonists of histamine H1 receptors].

The properties of 2,3,4,5-tetrahydro-1H-gamma-carbolines containing acid, ether, and amido-substituents, were assessed as potential antagonists of histamine H1 receptors (H1R), capable of blocking histamine-induced calcium fluxes in SK-N-SH cells. The structure--activity relationship for their antagonistic activity is discussed. Among the gamma-carbolines used in the study, the antihistamine activity considerably depends on the nature of substituents in positions 2, 5, and 8 of the heterocycle. The most active antagonist, ethyl 3-(2-methyl-8-fluoro-2,3,4,5-tetrahydro-1H-gamma-carboline-5-yl)propionate, with high affinity to the H1R (Ki = 6.5 nM), produces no adverse effects on motor activity of mice in doses 1-40 mg/kg, which shows the absence of a sedative effect.

[Correction of the glicemia level in elderly and senile patients with diabetes mellitus, operated for purulent-necrotic foot lesion].

Basing on the analysis of surgical treatment experience of 685 elderly and senile patients with diabetes mellitus, suffering purulent-necrotic affection of foot, the authors admit possibility of the insulinotherapy abolition before the operation in patients with for the first time diagnosed diabetes type II or in those, who before hospitalization received preparations in tablets, while the signs of intoxication are absent (extended purulent process, humid gangrene) and initial level of glycemia no more than 10 mmol/l.