Publications

Abstract The antiviral activity of (E)-5-(2-bromovinyl)-2′-deoxyuridine (BVdUrd), acyclovir and other antiherpetic nucleosides depends on a selective phosphorylation by the herpesvirus-induced thymidine kinase in the infected cells. Viruses not encoding a specific thymidine kinase (TK) activity are resistant to the action of these nucleoside analogues. The nucleoside monophosphates are as such poorly taken up by the cells. In order to circumvent the necessity of intracellular phosphorylation, we synthesized four core oligonucleotides bearing a biological active nucleoside at the 2′end. It was hypothesized that these core oligonucleotides, like core 2–5A itself, would be taken up within the cell and that, following intracellular 2′-5′ phosphodiesterase cleavage, the 5′-monophosphate of the active product would be formed. In these circumstances, activity against TK- strains could be expected.

Base plate preheating is one of the recent enhancing tools added to the process of Selective Laser Melting (SLM). This tool aims at a reduction of thermal stresses in SLM parts, achieved by decreasing the thermal gradients during SLM processing. In the current study, base plate preheating up to a temperature of 400°C is applied during SLM of 4 different materials, including aluminum 7075 alloy, nickel alloy Hastelloy X, H13 tool steel and CoCr. General trends, as well as material specific effects are discussed regarding part density, crack formation, internal stresses, microstructure and mechanical properties. These show how base plate preheating can induce different influences according to each particular material category.

The collaborative study was undertaken to examine the sensitivity of a range of tests used in assessing the antiviral activities of compounds against human immunodeficiency virus (HIV). A panel of 20 compounds with diverse antiviral activities against HIV were tested under code at three antiviral testing centres supported by the Medical Research Council's AIDS Directed Programme and at the European Community Centralised Facility (ECCF) for New Antiviral Compounds against AIDS in Belgium. Compounds known to have major anti-HIV activity ranked high in all assays, with the exception of the glucosidase inhibitors and certain nucleoside analogues. Results of two assays based on MT4 cells (centre IV) showed a high degree of similarity, despite the use of distinct HIV-1 (HTLV-III B ) and HIV-2 (ROD) viruses. Considerable similarity was also observed between the assays based on HTLV-III RF in C8166 cells (centres I and II). Other assays performed at centre II and at centre III had enhanced sensitivity for glycosidase inhibitors. The differences in anti-HIV activity that were observed may be attributable to specific properties of the cell lines used and particular testing methodologies. The use of more than one type of assay is advisable in order not to miss compounds with low to moderate activity against HIV.

Abstract For Abstract see ChemInform Abstract in Full Text.

The rabbit model of human cytomegalovirus (HCMV) retinitis was evaluated by preretinal and intravitreal injection of HCMV into rabbit eyes. Ocular disease was evaluated by indirect ophthalmoscopy, histopathology, and immunohistochemistry. Vitritis, optic nerve congestion, multiple small white infiltrates in the cortical vitreous or on the retinal surface, and retinal detachments were seen. Histopathologic examination showed inflammatory cell infiltration in the preretinal vitreous, optic nerve, and transiently in the superficial inner retina. Retinal structure was preserved except for changes in areas of retinal detachment. No necrosis or destruction of the retina was seen. Immunohistochemistry showed no evidence of cytomegalovirus infection. Inoculation of culture medium containing fetal calf serum caused a similar reaction. It is concluded that vitreous and retinal inoculation of HCMV in the rabbit eye caused nonspecific inflammation without evidence of infection, so this is not a suitable model for HCMV retinitis.