[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.

[The location of keratins 17 and 8 in the metaplastic proliferates of the endocervix]. / Lokalizatsiia keratinov 17 i 8 v metaplasticheskikh proliferatakh éndotserviksa sheiki matki.

Monoclonal antibodies to keratin 8 which is characteristic for glandular epithelium and those to keratin 17 characteristic of basal cells of complex epithelium were used. Material from 14 females after surgery because of ovarian tumours and uterine carcinoma and from 10 females with dysplasias of various degree and uterine carcinoma was investigated. In addition, ectocervix of vaginal portion at a distance from the point of two epithelia junction was studied in 42 samples. It is shown that keratins 8 and 17 are expressed in the ectocervix sporadically and have a basal location. Keratin 8 is expressed in column epithelium of the areas having normal structure of endocervix. Proliferation of subcolumn reserve cells is followed by an active expression of keratin 17. Proliferative multilayer areas with foci of the immature metaplasia, dysplasias and carcinoma in situ are characterized by cells with coexpression of both keratins, i.e. cells with double differentiation (glandular and squamous).