Dapsone, an old drug introduced and used almost exclusively for the treatment of leprosy, is now utilized in an increasing number of therapeutic situations. However, its hemotoxicity is potentially severe and is often dose limiting. Effective countermeasures, based on resolution of the mechanisms underlying dapsone-induced hemotoxicity, could significantly enhance the therapeutic value of the drug. In studies on rat red cells, we have established that the N-hydroxy metabolites of dapsone, DDS-NOH and MADDS-NOH, are direct-acting hemolytic agents, that they are formed in amounts sufficient to account for the hemotoxicity of the parent drug, and that the action of these toxic metabolites in the red cell induces premature sequestration by the spleen. Incubation of rat red cells with hemolytic concentrations of arylhydroxylamines leads to the generation of hydroxyl, glutathiyl, and hemoglobinthiyl radicals, and the formation of protein-glutathione mixed disulfides. Disulfide-linked adducts are also formed between membrane skeletal proteins and hemoglobin monomers, as well as between the monomeric hemoglobin units forming dimers, trimers, tetramers, and pentamers. Profound morphological changes are seen with change from normal discoidocity to an extreme nonspherocytic enchinocyte shape. Parallel studies with human red cells indicate that the response of human cells is qualitatively similar but that there are notable differences in regard to skeletal membrane effects. A working hypothesis for the mechanism underlying dapsone hemolytic activity is proposed.

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Acoustic emission is an emerging technique for condition monitoring of rolling element bearings and potentially offers advantages for detection of incipient damage at an early stage of failure. Before such a technique can be applied with confidence for health monitoring, it is vital to understand the variation of acoustic emission generation with operating conditions in a healthy bearing. This paper investigates the effects of increased speed and load on the generation of acoustic emission within cylindrical roller bearings, and it was found that the root mean square signal level increased significantly with increasing speed whereas increasing load had a far weaker effect. The AE RMS value for each experiment was compared with the trend of the Lambda value. The bearing was operating under full film lubrication regime, so it was determined that increases in AE RMS were not caused by asperity contact. By consideration of trends in frequency energy amplitude, it was determined that excitation of the bearings resonant frequencies were responsible for an increase of energy in the frequency range of 20-60 kHz. The excitation energy at 330 kHz (the acoustic emission sensor's resonant frequency) increased with load, indicating a link between high-frequency emission and stress at the contact zone. Following characterisation of the bearing under normal operating conditions, an accelerated life test was conducted in order to induce fatigue failure. The frequency response demonstrated that throughout a period of constant wear, the energy amplitude at the bearings resonant frequency increased with time. As the bearing failure became more significant, the energy of the high-frequency components above 100 kHz was spread over a broader frequency range as multiple transient bursts of energy were released simultaneously by fatigue failure of the raceways. This paper demonstrates the potential of acoustic emission to provide an insight into the bearing's behaviour under normal operation and provide early indication of bearing failure.

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