Speciation of As()/As(V) and Total Inorganic Arsenic in Biological Fluids Using New Mode of Liquid-Phase Microextraction and Electrothermal Atomic Absorption Spectrometry

In this paper, a new extraction method based on countercurrent liquid–liquid microextraction (CLLME) has been developed for the extraction and preconcentration of inorganic arsenic (iAs) in plasma and urine samples prior to their analysis by electrothermal atomic absorption spectrometry (ETAAS). In this method, firstly, 5 ml of water is added to the extraction vessel. Then 30.0 μl of the extracting solvent is added to it in order for the extracting solvent to be placed in the narrow-necked vessel. In total, 10 ml of a standard solution or a pretreated real sample is added to the sample container and it is connected to the extraction vessel via a connector. While opening the embedded valve at the bottom of the sample container and the one in the extraction vessel, the sample solution flows into the extracting solvent with the same flow rate, leading to the successful extraction of metal ligand into the extracting organic solvent. Under the optimum conditions, calibration curves are linear in the range of 0.1–50 μg l−1, and limit of detections (LODs) are in the range of 0.03–0.05 μg l−1. The enhancement factor and enrichment factor were in the range of 220–240 and 198–212, respectively. Repeatability (intra-day) and reproducibility (inter-day) of method based on seven replicate measurements of 5.0 μg l−1 of arsenic were in the range of 2.3–3.5% and 4.0–5.7%, respectively. The applicability of the proposed CLLME and ETAAS methods was demonstrated by analyzing the iAs in spiked urine and plasma samples. The obtained recoveries of the arsenic in the range of 92–107% indicated the excellent capability of the developed method for speciation of arsenic from plasma and urine sample

Inhibition of overactivated p38 MAPK can restore hematopoiesis in myelodysplastic syndrome progenitors

The myelodysplastic syndromes (MDSs) are collections of heterogeneous hematologic diseases characterized by refractory cytopenias as a result of ineffective hematopoiesis. Development of effective treatments has been impeded by limited insights into any unifying pathogenic pathways. We provide evidence that the p38 MAP kinase is constitutively activated or phosphorylated in MDS bone marrows. Such activation is uniformly observed in varied morphologic subtypes of low-risk MDS and correlates with enhanced apoptosis observed in MDS hematopoietic progenitors. Most importantly, pharmacologic inhibition of p38α by a novel small molecule inhibitor, SCIO-469, decreases apoptosis in MDS CD34+ progenitors and leads to dose-dependant increases in erythroid and myeloid colony formation. Down-regulation of the dominant p38α isoform by siRNA also leads to enhancement of hematopoiesis in MDS bone marrow progenitors in vitro. These data implicate p38 MAPK in the pathobiology of ineffective hematopoiesis in lowrisk MDS and provide a strong rationale for clinical investigation of SCIO-469 in MDS