The penetration of 5-ethyl-2'-deoxyuridine (edoxudine, Aedurid) from gel base with and without the addition of urea and other adjuvant has been studied in an in vitro model using guinea pig skin. The formulation of 3% edoxudine gel with 5% urea showed the best results. In vivo experiments on hairless mice infected intracutaneously with herpes simplex virus type 1 also showed this formulation's good efficacy as compared to other formulations.
The chemical syntheses of some 5-substituted uracil deorivatives, in particular 5-vinyl-2'-deoxyuridine, 5-ethynyl-2'-deoxyuridine and 4-(2-bromovinyl)-2'-deoxy-uridine are reviewed and their potential as radiation sensitizing agents, anti-cancer agents and antiviral agents is discussed. 5-Ethynyl-2'-deoxyuridine is not incorporated into DNA; is a thymidylate synthetase inhibitor and has a possible use as an anti-cancer drug. 5-Vinyl-2'-dexyuridine can replace thymidine residues in DNA of phage T3; does not cause the organism to be significantly more sensitive to gamma-radiation but its presence in DNA causes the organisms to be significantly more sensitive to gamma-radiation but its presence in DNA causes the organism to lose viability, possibly through chemical cross-linking reactions of the vinyl group. 5-(2-Bromovinyl)-2'-deoxyuridine is the most specific and potent antiherpes compound yet known. Its mode of action and its affects on herpes virus in vitro and in vivo with animal models and clinical observations are described.
The proposed self-calibration method uses an artefact, a ball plate, for error identification. Unlike other methods this ball plate need not be calibrated, i.e. the distances between the different balls on the plate need not be known accurately. After measurement of the ball plate in different positions within the measuring volume, the systematic geometrical errors, like scale errors, axes' pitch, yaw and non-orthogonality, of the geometric error model of the measuring machine can be calculated. This geometrical error model is used afterwards by the software error correction to correct on-line every single measurement carried by the measuring machine. This results in a higher accuracy of the measurement. As an example, the self-calibration method has been carried out on a CNC 3-D coordinate measuring machine and the resulting software error correction has been evaluated using step-gauge measurements. The results of the evaluation show that the systematic geometrical errors are greatly reduced.
Numerous structurally different non-nucleoside compounds have been evaluated for their inhibitory effects against HIV replication, in which DABO derivatives, bearing the dihydro-alkoxyl-benzyl-oxopyrimidine scaffold, have been identified as a particular class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). The S-DABO, NH-DABO, -N-DABO, DATNO and DACO analogs represent various structural chemical modifications of the substituents on C2, C6 and C5 of the pyrimidine ring to obtain potentially higher potency and lower cytotoxicity. This review article describes the recent progress of the chemical modifications and structure-activity relationship studies of DABO derivatives and provides new clues for the design of new DABO congeners.
