Management of post-operative Nocardia endophthalmitis.

Post-operative Nocardia endophthalmitis has an aggressive course and poor visual prognosis. It often masquerades as severe post-operative uveitis or toxic anterior segment syndrome due to the absence of vitreous involvement resulting in a delay in diagnosis. The poor prognosis in Nocardia endophthalmitis is due to severe intra-ocular inflammation which may lead to phthisis. Therefore, treatment with corticosteroids after appropriate antibiotics have been initiated may improve the outcome. This is an interventional case report highlighting the typical features of Nocardia endophthalmitis, which when diagnosed early and managed medically with antibiotics and steroids, resulted in an excellent visual outcome in our patient.

Inhibition of c-Myc expression sensitizes hepatocytes to tumor necrosis factor-induced apoptosis and necrosis.

The typical proliferative response of hepatocytes to tumor necrosis factor (TNF) can be converted to a cytotoxic one by transcriptional arrest. Although NF-kappaB activation is critical for hepatocyte resistance to TNF toxicity, the contribution of other TNF-inducible transcription factors remains unknown. To determine the function of c-Myc in hepatocyte sensitivity to TNF, stable transfectants of the rat hepatocyte cell line RALA255-10G containing sense and antisense c-myc expression vectors were isolated with increased (S-Myc cells) and decreased (AN-Myc cells) c-Myc transcriptional activity. While S-Myc cells proliferated in response to TNF treatment, AN-Myc cells underwent 32% cell death within 6 h. Fluorescent microscopic studies indicated that TNF induced apoptosis and necrosis in AN-Myc cells. Cell death was associated with DNA hypoploidy and poly(ADP-ribose) polymerase cleavage but occurred in the absence of detectable caspase-3, -7, or -8 activation. TNF-induced, AN-Myc cell death was dependent on Fas-associated protein with death domain and partially blocked by caspase inhibitors. AN-Myc cells had decreased levels of NF-kappaB transcriptional activity, but S-Myc cells maintained resistance to TNF despite NF-kappaB inactivation, suggesting that c-Myc and NF-kappaB independently mediate TNF resistance. Thus, in the absence of sufficient c-Myc expression, hepatocytes are sensitized to TNF-induced apoptosis and necrosis. These findings demonstrate that hepatocyte resistance to TNF is regulated by multiple transcriptional activators.

Role of caspases and NF-kappaB signaling in hydrogen peroxide- and superoxide-induced hepatocyte apoptosis.

Reactive oxygen intermediates (ROI) have been implicated as mediators of hepatocyte death resulting from a variety of forms of liver injury. To delineate the mechanisms that underlie ROI-induced apoptosis, the roles of caspase activation and nuclear factor-kappaB (NF-kappaB) signaling were determined in the rat hepatocyte cell line RALA255-10G after treatment with H(2)O(2) or the superoxide generator menadione. By 8 h, H(2)O(2) and menadione caused 26% and 33% cell death, respectively. Death from both ROI occurred by apoptosis as indicated by morphology under fluorescence microscopy, the induction of caspase activation and DNA fragmentation, and the cleavage of poly(ADP-ribose) polymerase. Despite the presence of caspase activation in both forms of apoptosis, caspase inhibition blocked H(2)O(2)- but not menadione-induced apoptosis. In contrast, inhibition of NF-kappaB activation decreased cell death from both ROI. Different ROI, therefore, induce distinct apoptotic pathways in RALA hepatocytes that are both caspase dependent and independent. In contrast to the known protective effect of NF-kappaB activation in tumor necrosis factor-alpha-induced hepatocyte apoptosis, NF-kappaB promotes hepatocellular death from ROI in these cells.