A study of arsenic speciation in soil, irrigation water and plant tissue: A case study of the broad bean plant, Vicia faba.

Samples of soil, the broad bean plant, Vicia faba and irrigation water were collected from the same agricultural site in Dokan, in the Kurdistan region of Iraq. Total arsenic and arsenic speciation were determined in all materials by ICP-MS and HPLC-ICP-MS, respectively. Available arsenic (11%) was also determined within the soil, together with Cd, Cr, Cu, Ni, Zn, Fe and Mn. The concentrations of total arsenic were: soil (5.32μgg(-1)), irrigation water (1.06μgL(-1)), roots (2.065μgg(-1)) and bean (0.133μgg(-1)). Stems, leaves and pods were also measured. Inorganic As(V) dominated soil (90%) and root (78%) samples. However, organo-arsenic (MMA, 48% and DMA, 19%) was the more dominant species in the edible bean. The study provides an insight into the uptake, preferred disposal route, speciation changes and loss mechanism involved for arsenic with this food source

Flavopiridol Pharmacogenetics: Clinical and Functional Evidence for the Role of SLCO1B1/OATP1B1 in Flavopiridol Disposition

Flavopiridol is a cyclin-dependent kinase inhibitor in phase II clinical development for treatment of various forms of cancer. When administered with a pharmacokinetically (PK)-directed dosing schedule, flavopiridol exhibited striking activity in patients with refractory chronic lymphocytic leukemia. This study aimed to evaluate pharmacogenetic factors associated with inter-individual variability in pharmacokinetics and outcomes associated with flavopiridol therapy.Thirty-five patients who received single-agent flavopiridol via the PK-directed schedule were genotyped for 189 polymorphisms in genes encoding 56 drug metabolizing enzymes and transporters. Genotypes were evaluated in univariate and multivariate analyses as covariates in a population PK model. Transport of flavopiridol and its glucuronide metabolite was evaluated in uptake assays in HEK-293 and MDCK-II cells transiently transfected with SLCO1B1. Polymorphisms in ABCC2, ABCG2, UGT1A1, UGT1A9, and SLCO1B1 were found to significantly correlate with flavopiridol PK in univariate analysis. Transport assay results indicated both flavopiridol and flavopiridol-glucuronide are substrates of the SLCO1B1/OATP1B1 transporter. Covariates incorporated into the final population PK model included bilirubin, SLCO1B1 rs11045819 and ABCC2 rs8187710. Associations were also observed between genotype and response. To validate these findings, a second set of data with 51 patients was evaluated, and overall trends for associations between PK and PGx were found to be consistent.Polymorphisms in transport genes were found to be associated with flavopiridol disposition and outcomes. Observed clinical associations with SLCO1B1 were functionally validated indicating for the first time its relevance as a transporter of flavopiridol and its glucuronide metabolite. A second 51-patient dataset indicated similar trends between genotype in the SLCO1B1 and other candidate genes, thus providing support for these findings. Further study in larger patient populations will be necessary to fully characterize and validate the clinical impact of polymorphisms in SLCO1B1 and other transporter and metabolizing enzyme genes on outcomes from flavopiridol therapy

Arsenic speciation and its DNA fractionation in the rice plant: Oryza sativa

The transport of arsenic from soil through to edible crop is important when assessing the potential health risks from a food source. Samples of soil, irrigation water and the rice plant, Oryza sativa, were collected from an agricultural site in the Middle East. Total As, its speciation and DNA fractionation were evaluated using HPLC-ICP-MS in samples which included the root, stem, leaf and grain of the rice plant. Methodology was validated through the use of CRMs. The highest concentration of As was found in the root of the plant and the lowest in the grain. The concentrations found for As were: soil (aqua-regia extractable; 2.88 μg g-1), irrigation water (0.58 μg L-1), roots (8.28 μg g-1), stem (4.00 μg g-1), leaves (2.93 μg g-1) and grain (1.02 μg g-1). Levels of inorganic AsV and AsIII were identified in the soil and plant material, while organo-arsenic species (DMA, MMA) were below the limit of detection. The 'plant available' levels of As in the soil (14%) were determined as part of a full, validated BCR three-step sequential extraction procedure. Since As can behave as a phosphate analogue, a method was developed for the extraction of vegetative DNA to determine the different forms of As associated with, or integrated within, the DNA fractions. Measurement of As in the DNA extracts were above the LOD (0.019 μg kg-1) for the root, stem and leaf samples. The concentration of both weakly and strongly associated As with DNA obtained from the root, stem and leaf decreased with decreasing total As concentrations. A narrow, near-constant ratio for the strongly associated As value (As/total As DNA) in all root, stem and leaf DNA samples (41.3 ± 0.3%) was further evidence for the incorporation of As into the DNA

Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease

Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa (L-dopa) therapy for Parkinson’s disease (PD). L-dopa-induced dyskinesia (LID) are ultimately experienced by the vast majority of patients. In addition, psychiatric conditions often manifested as compulsive behaviours, are emerging as a serious problem in the management of L-dopa therapy. The present review attempts to provide an overview of our current understanding of dyskinesia and other L-dopa-induced dysfunctions, a field that dramatically evolved in the past twenty years. In view of the extensive literature on LID, there appeared a critical need to re-frame the concepts, to highlight the most suitable models, to review the central nervous system (CNS) circuitry that may be involved, and to propose a pathophysiological framework was timely and necessary. An updated review to clarify our understanding of LID and other L-dopa-related side effects was therefore timely and necessary. This review should help in the development of novel therapeutic strategies aimed at preventing the generation of dyskinetic symptom