Publications

In vitro evaluation of the novel cycloalkyl-N-(4-chlorophenyl)-hydroxamic acids (2a-g) demonstrated that 2b,d,e exhibited rather marked inhibitory activity (IC50 = 7-10 microM) against pancreatic carcinoma, 2b-d against colon carcinoma, 2d against laryngeal carcinoma, and 2b,d against breast carcinoma. 2e showed the most pronounced anti-cytomegalovirus activity (EC50 = 1.5 and 0.8 microg mL(-1)) only at > or = 5-fold lower than the cytotoxic concentration. 2d and 2f showed modest, albeit selective, activity against cytomegalovirus (2d, EC50 = 7.3-8.9 microg mL(-1), selectivity index 7-10; 2f, EC50 = 7-13 microg mL(-1), selectivity index 10).

An 8-year-old patient with severe recurrent respiratory papillomatosis and pulmonary spread was treated by systemic administration of cidofovir in association with laser treatment for tracheal lesions. Complete disappearance of the lesions in the pharynx and larynx and a significant yet incomplete regression in the bronchi and lung parenchyma were observed without deleterious side effects. This is the first case report of systemic use of cidofovir to treat recurrent respiratory papillomatosis.

A series of acyclic nucleoside phosphonate (ANP) and 2',3'-dideoxynucleoside (ddN) derivatives were evaluated for their inhibitory effects on visna virus replication and maedi/visna virus-induced syncytium formation in sheep choroid plexus cells. Most ANP derivatives inhibited virus replication and syncytium formation within a concentration range of 0.2 to 1.8 microM. Among the most active ANP derivatives ranked (R)-9-(2-phosphonomethoxypropyl)adenine, (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine, and (S)-9-(3-fluoro-2-phosphonomethoxypropyl)adenine. Of the ddN derivatives, 2',3'-dideoxycytidine (ddCyd) proved to be the most inhibitory to visna virus-induced syncytium formation (50% effective concentration, 0.02 microM). The purine ddN analogs (i.e., 2',3'-dideoxyinosine, 2',3'-dideoxyadenosine, 2',3'-dideoxyguanosine, and 2,6-diaminopurine-2',3'-dideoxyribosine) were 10- to 30-fold less effective, and the thymidine derivatives 2',3'-didehydro-2',3'-dideoxythymidine (D4T) and 3'-azido-2',3'-dideoxythymidine (AZT) were more than 500-fold less inhibitory to visna virus than ddCyd. The 5'-triphosphate forms of AZT and D4T were 100- to 600-fold more inhibitory to visna virus particle-derived reverse transcriptase than was the 5'-triphosphate of ddCyd. The apparent discrepancy between the inhibitory effects of these ddN derivatives on virus replication and viral reverse transcriptase activity most likely reflects differences in the metabolic conversion of ddCyd versus D4T and AZT in sheep choroid plexus cells.

Selective laser melting (SLM) is an additive manufacturing technique in which metal products are manufactured in a layer-by-layer manner. One of the main advantages of SLM is the large geometrical design freedom. Because of the layered build, parts with inner cavities can be produced. However, complex structures, such as downfacing areas, influence the process behavior significantly. The downfacing areas can be either horizontal or inclined structures. The first part of this work describes the process parameter optimization for noncomplex, upfacing structures to obtain relative densities above 99%. In the second part of this research, parameters are optimized for downfacing areas, both horizontal and inclined. The experimental results are compared to simulations of a thermal model, which calculates the melt pool dimensions based on the material properties (such as thermal conductivity) and process parameters (such as laser power and scan speed). The simulations show a great similarity between the thermal model and the actual process.

Click to increase image sizeClick to decrease image sizeKeywords: Acknowledgments The Spanish CICYT, the Comunidad de Madrid (CAM) and the European Commission are acknowledged for financial support. The European Commission is also acknowledged for the René Descartes-2001 Prize.