No abstract

Plant polyphenols have been shown to enhance the differentiation of acute myeloid leukemia (AML) cells induced by the hormonal form of vitamin D3 (1α,25-dihydroxyvitamin D3; 1,25D). However, how these agents modulate 1,25D effects in different subtypes of AML cells remains poorly understood. Here, we show that both carnosic acid (CA) and silibinin (SIL) synergistically enhancd 1,25D-induced differentiation of myeloblastic HL60 cells. However, in promonocytic U937 cells, only CA caused potentiation while SIL attenuated 1,25D effect. The enhanced effect of 1,25D+CA was accompanied by increases in both the vitamin D receptor (VDR) and retinoid X receptor alpha (RXRα) protein levels and vitamin D response element (VDRE) transactivation in both cell lines. Similar increases were observed in HL60 cells treated with 1,25D + SIL. In U937 cells, however, SIL inhibited 1,25D-induced VDRE transactivation concomitant with downregulation of RXRα at both transcriptional and posttranscriptional levels. These inhibitory effects correlated with the inability of SIL, with or without 1,25D, to activate the Nrf2/antioxidant response element signaling pathway in U937 cells. These results suggest that opposite effects of SIL on 1,25D-induced differentiation of HL60 and U937 cells may be determined by cell-type-specific signaling and transcriptional responses to this polyphenol resulting in differential modulation of RXRα expression.

A continuous-flow clinical analyzer for the routine estimation of urea is described that makes use of an immobilized-enzyme nylon-tube reactor as part of a flow-through system (a Technicon AutoAnalyzer I). Results of blood-urea analyses by use of the immobilized urease are compared with determinations made with the diacetyl monoxime method and the urease solution method. Clinical trials carried out routinely with the immobilized enzyme nylon tube reactor give reliable and reproducible results with high precision and low cost. The reactors are stable to intermittent or continued use for at least four months or for 2000 tests. A method is described in which differential colorimetry is used for determining citrulline in blood and which makes use of the immobilized urease, albeit indirectly.