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A 46-year-old woman was diagnosed with acute promyelocytic leukemia (APL). The patient was given remission induction therapy with all-trans retinoic acid, and complete remission was achieved. Despite consolidation therapies with arsenic trioxide, daunorubicin and cytosine arabinoside (AraC), and gemtuzumab ozogamicin as well as maintenance therapy with tamibarotene, the patient experienced a relapse 6 months after the start of maintenance therapy. She was then given re-induction therapy with idarubicin+AraC and high-dose AraC, but remission was not achieved. Since the coordination of the unrelated donor had been completed at this time, she then underwent bone marrow transplantation with pre-conditioning of 4 Gy total body irradiation, fludarabine, and busulfan. However, on the 12th day after the transplantation, APL cells appeared in the peripheral blood and the disease progressed rapidly leading to the patient's death on the 15th day after the transplantation. APL usually has a good prognosis, and relapsed cases are often cured by autologous stem cell transplantation. However, this case was highly refractory to treatment and the patient deteriorated rapidly after the transplantation, suggesting a different pathogenesis from the usual from of APL.

Aim: To evaluate the neuroprotective effect of a dietary supplement (ClearVision EX ® ; CV) against glutamate-induced excitotoxicity in retina., Methods: We evaluated the protective effects CV on glutamate-induced cell toxicity of an immortalized mouse hippocampal cell line (HT-22) in vitro and N-methyl-D-aspartate (NMDA) induced retinal injury in vivo . Once-daily oral administration of CV or vehicle (5% Arabic gum) was started the day before the NMDA injection and continued until the end of the study. Electroretinograms (ERGs) were recorded to evaluate the retinal function at 2d after NMDA injection. Furthermore, a histological evaluation, Western blot analysis, and immunohistochemistry were performed for assessing the signal transduction pathway., Results: HT-22 cell death was induced by the addition of glutamate and co-incubation with CV protected against it. Oral administration of CV inhibited the decrease in scotopic threshold response amplitudes induced by the intravitreal injection of NMDA and those of the thickness of the inner retinal layer in the histological evaluation. The increased phosphorylated levels of extracellular signal-regulated kinase (ERK) but not cAMP response element binding protein (CREB) or Akt were observed 1h after NMDA injection in both the vehicle- and CV-treated rats; however, pERK activation was no more upregulated at 3h after NMDA injection. pERK upregulation was observed in Müller cells., Conclusion: CV shows a protective effect against both glutamate-induced HT-22 cell death and NMDA-induced retinal damage. pERK upregulation in the Müller cells plays a key role in the protective effect of CV against glutamate-induced retinal toxicity.

N -methyl- N -nitrosourea (MNU), a known carcinogen, is generally used in animal models to chemically induce photoreceptor degeneration. It has been reported that nicotinamide (NAM) exerts a protective effect on MNU-induced photoreceptor degeneration. We investigated the molecular mechanisms on MNU-induced photoreceptor degeneration. Intraperitoneal MNU injection (75 mg/kg) in rats induced selective photoreceptor degeneration in 7 days. NAM administration completely inhibited photoreceptor degeneration. Photoreceptor layer abnormality was observed within 6 hours after MNU injection, whereas it was restored in the NAM-treated retina, as detected by optical coherence tomography. One day following MNU administration, phosphorylation of the cell death-associated signalling proteins c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) increased, while the apoptosis-related proteins, full-length poly(ADP-ribose) polymerase (PARP) and apoptosis-inducing factor (AIF), were depleted. These changes were not observed in the NAM-treated retinas. Cell survival signalling, such as extracellular signal-regulated kinase (ERK), Akt, and cAMP response element binding protein (CREB) phosphorylation, increased in the MNU- but not in the NAM-treated rat retinas. Increased phosphorylated ERK (p-ERK) levels were observed within 6 hours after MNU administration, suggestive of cell survival signalling activation. This did not occur in NAM-treated retinas. These results indicate that NAM regulates upstream cellular events prior to the activation of cell death-related signalling events, such as JNK and p38 phosphorylation.