The cytotoxic macrolide FD-891 induces caspase-8-dependent mitochondrial release of cytochrome c and subsequent apoptosis in human leukemia Jurkat cells.

The 16-membered macrolide FD-891 exerts cytotoxicity toward several cancer cell lines. In this study, we showed that FD-891 induces apoptosis in various human cancer cell lines. Human leukemia Jurkat cells were highly sensitive to FD-891, exhibiting caspase activation and mitochondrial release of cytochrome c into the cytosol at early time points after exposure to FD-891. By contrast, Jurkat cells deficient in caspase-8 were resistant to FD-891-induced apoptosis and manifested little induction of cytochrome c release as well as caspase-9 processing. Consistent with these results, the overexpression of the Bcl-2 family member Bcl-x(L) or the caspase-8 modulator c-FLIP(L) markedly prevented FD-891-induced apoptosis. These results clearly demonstrate that FD-891 triggers caspase-8-dependent mitochondrial release of cytochrome c and subsequent apoptosis in Jurkat cells.

[Intra-operative ketamine administration reduced the level of post-thoracotomy pain].

BACKGROUND: Two different types of post-operative pain (such as acute pain and chronic pain) occur in patients undergoing thoracotomy. It has been suggested that the acute post-thoracotomy pain consists of inflammatory pain and chronic post-thoracotomy pain caused by intercostal neuralgia. In the present study, we examined the effect of intra-operative administration of ketamine, an NMDA receptor antagonist, on the acute and chronic post-thoracotomy pain. METHODS: Sixteen patients were assigned to one of two groups (ketamine or control). The ketamine group received a ketamine bolus (1 mg x kg(-1)) just before the skin incision, followed by continuous infusion of ketamine (1 mg x kg(-1) x hr(-1)) during surgery. RESULTS: Verbal rating scores (VRSs) at rest and on cough were significantly lower in the ketamine group on day 1 and VRS of chronic pain was also significantly lower in the ketamine group 4 weeks after the surgery. CONCLUSIONS: These data suggest that post-thoracotomy pain might be mediated by NMDA receptor dependent central sensitization and that the intra-operative administration of ketamine might block the development of the NMDA receptor dependent central sensitization.

Vesicoureteral junction obstruction associated with unilateral renal agenesis.

A 7-month-old boy with a solitary kidney showed recurrent urinary tract infection. Magnetic resonance urography helps in the identification of vesicoureteral junction obstruction associated with unilateral renal agenesis.