Publications

The novel purine derivatives of 1- aminocyclopropane-1-carboxylic acid (8 and 9) and 1-amino-1-hydroxymethylcyclopropane (12 and 13) with methylene spacer between the base and the cyclopropane ring were prepared by multistep synthetic route involving alkylation of adenine and 6-(N-pyrrolyl)purine with 2-hydroxymethyl-1- aminocyclopropane-1-carboxylic acid derivative 3 as a key reaction. The N-9 substitution of the purine ring and the Z-configuration of the cyclopropane ring in 4-13 were deduced from their 1H and 13C NMR spectra by analyses of chemical shifts, H-H coupling constants and connectivities in two-dimensional homo- and heteronuclear correlation spectra. An unequivocal proof of the stereostructure of 1, 4 and 5 was obtained by their X-ray structure analysis. The novel compounds were evaluated on cytostatic and antiviral activities in several cell lines. The 6- (N-pyrrolyl)purine derivative of 1, 2- aminocyclopropane alcohol 12 exhibited a more pronounced inhibitory activity against the proliferation of cervical carcinoma (HeLa) and human fibroblast (WI-38) cells than other types of tumor cell lines. None of the compounds showed inhibitory activities against cytomegalovirus, varicella-zoster virus or other viruses.

Novel 5,6-dichlorobenzimidazole nucleoside analogues structurally related to the well-known riboside DRB have been synthesized. The 1′,2′- trans nucleosides were prepared by condensation of peracylated sugars with 5,6-dichlorobenzimidazole, whereas the 1′,2′- cis β-D-arabinofuranosyl and β-D-lyxofuranosyl nucleosides were obtained by inversion of configuration on the sugar moiety. Chiral acyclic derivatives were stereospecifically prepared by ring-opening of furano- or pyrano-nucleosides by means of periodate oxidation, followed by borohydride reduction. The in vitro activities against a range of DNA and RNA viruses, as well as the cytotoxicities in human T-lymphocyte MT-4 cells, have been determined for these novel compounds and for DRB. No truly selective activity (i.e. clearly below the cytotoxic concentration) was observed against any of the viruses used. Some of the compounds, including DRB, were cytotoxic to MT-4 cells at CC 50 values of less than 10 μg ml −1 .

Among thirteen newly synthesized pyridobenzoazole derivatives which have been examined for anti-myxovirus and antiherpesvirus activities, three benzimidazoles emerged as potent anti-orthomyxo- or paramyxovirus compounds. 4-Cyano-2-benzamide-1-oxo-1,5-dihydropyrido[1,2a]benzimidazole (CBO-PB) showed broad antiviral activities against paramyxo-and orthomyxoviruses with EC 50 of 0.1–2.0 μg ml −1 , and 2-cyano-1-amino derivatives of CBO-PB (CCI-PB) were inhibitory to paramyxoviruses at 1.4–8.5 (μg ml −1 by a plaque reduction method. The third compound, 2-ethoxycarbonyl derivatives of CCI-PB was inhibitory only to respiratory syncytial virus (RSV) at 15–28 μg ml −1 . Selectivity indexes of these 3 compounds for RSV in HeLa cells were 60, 86, and >13, respectively. All three compounds inhibited syncytium formation of RSV and Parainfluenzavirus (PFLUV) type 3 at comparable concentrations with EC 50 for plaque formation. They inhibited antigen production of RSV and PFLUV at the concentrations that were 4 to 20-fold higher than those needed for plaque reduction, but they did not inhibit adsorption of virus to cells at all. All three compounds inhibited the growth of RSV in HeLa cells at 4-fold higher concentrations than their EC 50 for plaque reduction.

Selective laser melting has been applied as a production technique of nickel titanium (NiTi) parts. In this study, the scanning parameters and atmosphere c

The therapeutic efficacy of three new antiviral agents-5-iodo-3',5'-diacetyl-2'-deoxyuridine (diacetylidoxuridine, 1% Ac2IDU), E-5-(2-bromovinyl)-2'-deoxyuridine (0.25% BVDU), and 3% thymine arabinoside-is compared with available antivirals in an experimental model of herpes simplex virus type 1 (HSV-1) keratitis in New Zealand white rabbits. Compared with placebo, Ac2IDU significantly reduced ulcerative keratitis on days 4 through 8 after inoculation with virus and iritis on day 8 after inoculation. Compared with placebo, thymine arabinoside reduced ulcerative keratitis but not significantly. Thymine arabinoside caused significant iritis in all eyes. The epithelial disease in BVDU-treated eyes was significantly less than that in placebo-treated eyes on days 5 through 8 after inoculation. The results indicate that 1% Ac2IDU and 0.25% BVDU were effective in our ocular model of HSV-1 keratitis, whereas thymine arabinoside was not.

X-ray computed tomography (CT) is slowly conquering its space in the manufacturing industry for dimensional metrology and quality control purposes. The main advantage is its non-invasive and non-destructive character. Currently, CT is the only measurement technique that allows full 3D visualization of both inner and outer features of an object through a contactless probing system. Using hundreds of radiographs, acquired while rotating the object, a 3D representation is generated and dimensions can be verified. In this research, this non-contact technique was used for the inspection of assembled components. A dental cast model with 8 implants, connected by a screwed retained bar made of titanium. The retained bar includes a mating interface connection that should ensure a perfect fitting without residual stresses when the connection is fixed with screws. CT was used to inspect the mating interfaces between these two components. Gaps at the connections can lead to bacterial growth and potential inconvenience for the patient who would have to face a new surgery to replace his/hers prosthesis. With the aid of CT, flaws in the design or manufacturing process that could lead to gaps at the connections could be assessed.

The level of HIV-1 RNA in plasma has become one of the most important markers in the follow-up of HIV-infected patients. Three techniques are commercially available: both the Amplicor HIV Monitor and the NASBA HIV-1 RNA QT are target amplification methods, whereas the Quantiplex HIV RNA assay is a branched DNA signal amplification technique. Detection in both target amplification techniques is based on a single primer pair and a single probe in the gag region, whereas multiple probes capture the pol region of the viral RNA in the branched DNA assay. We investigated the discrepant observation of an undetectable viral load in an immunodeficient pregnant HIV-1-infected patient of African origin with no prior antiretroviral treatment. Although clinical progression was present in this patient with tuberculosis and a low CD4 cell count, viral load determinations with both the Amplicor Monitor and NASBA assays revealed no detectable RNA levels. The presence of HIV-1 RNA in the plasma of the patient was demonstrated by an in-house RNA-PCR. Subsequent HIV-1 RNA quantification with the branched DNA method revealed a high viremia (460,000 copies/ml). DNA sequence analysis of the gag gene identified a subtype G HIV-1 strain (HIV-1BL). To our knowledge this is the first report of a patient harboring an HIV-1 genotype of the main group with a high viral load as quantified by the branched DNA assay, but undetectable with the two commercial HIV RNA amplification techniques because of genetic divergence. In the case of discrepant low viral loads determined by one amplification technique in patients with advanced clinical stage one should use an alternative quantification technique for confirmation.