[Lead poisoning associated with an Indian-manufactured unauthorized dietary supplement].

We report the case of a patient with lead poisoning caused by a dietary supplement. A 40-year-old man was referred to us due to intermittent upper abdominal pain and normocytic anemia. His hemoglobin level was 9.3 g/dl, with basophilic stippling in 2.8% of red blood cells. Bone marrow aspirate smear showed ringed sideroblasts that represented 19% of the erythroblasts. The patient reported the use of an unauthorized, Indian-manufactured dietary supplement and was diagnosed with lead poisoning based on a significantly high blood lead level. The dietary supplement was discontinued, and he was successfully treated with lead chelation therapy, and his hemoglobin level normalized within 2 months.

Prognostic impact and targeting of CRM1 in acute myeloid leukemia.

Chromosomal region maintenance 1 (CRM1) is a nuclear export receptor recognizing proteins bearing a leucine-rich nuclear export signal. CRM1 is involved in nuclear export of tumor suppressors such as p53. We investigated the prognostic significance of CRM1 in acute myeloid leukemia (AML) and effects of a novel small-molecule selective inhibitor of CRM1. CRM1 protein expression was determined in 511 newly diagnosed AML patients and was correlated with mouse double minute 2 (MDM2) and p53 levels. High CRM1 expression was associated with short survival of patients and remained an adverse prognostic factor in multivariate analysis. CRM1 inhibitor KPT-185 induced mainly full-length p53 and apoptosis in a p53-dependent manner, whereas inhibition of proliferation was p53 independent. Patient samples with p53 mutations showed low sensitivity to KPT-185. Nuclear retention of p53 induced by CRM1 inhibition synergized with increased levels of p53 induced by MDM2 inhibition in apoptosis induction. KPT-185 and Nutlin-3a, alone and in combination, induced synergistic apoptosis in patient-derived CD34(+)/CD38(-) AML, but not in normal progenitor cells. Data suggest that CRM1 exerts an antiapoptotic function and is highly prognostic in AML. We propose a novel combinatorial approach for the therapy of AML, aimed at maximal activation of p53-mediated apoptosis by concomitant MDM2 and CRM1 inhibition.

An on-chip cardiomyocyte cell network assay for stable drug screening regarding community effect of cell network size.

We investigate the effect of haloperidol on a four-cell and nine-cell cardiomyocyte network on an agarose microchamber array chip to evaluate a cell-based model for drug screening. Using a network of cardiomyocytes whose beating intervals were stable and relatively uniform (they only fluctuated 10% from the mean beating interval), we easily observed the effect of haloperidol on the cell network beating interval 5 min after administering it. We also observed the beating interval returned to its original state 10 min after the haloperidol was washed out of the chip. Although the four-cell network showed the unstable recovery of its beating rhythm after washout of haloperidol, the nine-cell network recovered completely to the stable original beating rhythm even after a second administration of haloperidol. The results indicate the importance of the community size in cell networks used in the stable cell-based screening model. Moreover, they indicate the advantage of using direct cell-based measurements in which the amount of drug administered and the time course over which it is administered are strictly controlled for evaluating the quantitative chemical effects of drugs on cells.