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Despite the increasing industrial use of indium-tin oxide (ITO) to manufacture flatpanel displays, such as liquid-crystal displays or plasma display panels for televisions, little is known about the potential health hazard induced by occupational exposure to indium compounds.The current study describes a case of fibrotic lung disease that developed after a 4-yr exposure to ITO. The pathology of the lung demonstrated pulmonary fibrosis with the presence of cholesterol granulomas.In conclusion, more attention needs to be paid to the possible toxic effects of indium compounds, and maximum healthcare measures should be taken to protect industry workers from these toxicities.KEYWORDS: Cholesterol granuloma, human, indium-tin oxide, lung injury, pulmonary fibrosis I ndium belongs to Group III in the periodic table and is mainly used in the manufacture of flat-panel displays, such as liquid-crystal displays or plasma display panels for television screens, computer screens and video monitors [1,2]. In these displays, indium-tin oxide (ITO) is utilised for transparent conductive films. In light of the recent growth of the market due to the increasing use of liquid-crystal displays in personal computer screens and plasma display panels in wall-mounted televisions, the demand for ITO has risen sharply. As industrial consumption of ITO rises, the potential health hazard caused by occupational exposure to indium compounds has been attracting much more attention than before. However, in the literature, there have been a limited number of reports of pulmonary toxicity by ITO, including only one autopsied human case with occupational exposure to indium compounds [3], and a few preliminary animal studies on the lung toxicity of indium [4][5][6][7][8][9]. In the present study, a previously healthy young male with lung injury, probably caused by inhalation of ITO, is described. CASE PRESENTATIONIn January 2002, a 30-yr-old male engineer visited the current authors' hospital (Dept of Respiratory Medicine, Respiratory Centre, Toranomon Hospital, Tokyo, Japan) complaining of dry cough and exertional dyspnoea, which he had been experiencing since 1997. He had a minimum history of cigarette smoking (3 cigarettes?day -1 for 3 yrs). From 1994 to 1998, he had been exposed to indium compounds (i.e. ITO) as an aerosol while making transparent conductive films. Physical examination of the chest on admission revealed normal vesicular breath sounds and the absence of finger clubbing. Pulmonary function tests and arterial blood gas analysis in room air yielded normal values: a vital capacity of 4.18 L (93% predicted), forced expiratory volume in one second of 3.07 L (73% pred), residual volume (RV) of 2.20 L (measured by the gas dilution method; 158% pred), total lung capacity (TLC) of 6.38 L (109% pred), RV/TLC ratio of 34%, carbon dioxide diffusing capacity of the lung of 3.21 mL?min -1 ?kPa (89% pred), pH 7.40, arterial oxygen tension of 11.8 kPa, and arterial carbon dioxide tension of 5.3 kPa [10]. Peripheral blood examination sho...

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Thalidomide possesses two optical isomers which have been reported to exhibit different pharmacological and toxicological activities. However, the precise mechanism by which the two isomers exert their different activities remains poorly understood. Here, we present structural and biochemical studies of (S)- and (R)-enantiomers bound to the primary target of thalidomide, cereblon (CRBN). Our biochemical studies employed deuterium-substituted thalidomides to suppress optical isomer conversion, and established that the (S)-enantiomer exhibited ~10-fold stronger binding to CRBN and inhibition of self-ubiquitylation compared to the (R)-enantiomer. The crystal structures of the thalidomide-binding domain of CRBN bound to each enantiomer show that both enantiomers bind the tri-Trp pocket, although the bound form of the (S)-enantiomer exhibited a more relaxed glutarimide ring conformation. The (S)-enantiomer induced greater teratogenic effects on fins of zebrafish compared to the (R)-enantiomer. This study has established a mechanism by which thalidomide exerts its effects in a stereospecific manner at the atomic level.

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