Coupled techniques for arsenic speciation in food and drinking water: A review

Arsenic is ubiquitous in nature appearing in various chemical forms. The toxicity, environmental mobility and accumulation of As in living organisms depends on the form in which the element exists, thus requiring techniques which can identify specific forms whilst retaining their integrity during extraction and pre-treatment prior to measurement. Both organic and inorganic arsenic species may be present in food staples of both terrestrial and marine origin as well as natural waters, at sub ng l-1 to high mg l-1 levels. In this review, the speciation steps (sample preparation, species speciation and detection) most commonly used for the determination of As in food are described. High performance liquid chromatography separation with plasma source mass spectrometry is often the technique of choice due to its versatility, robustness and good detection limits. However, detection systems such as atomic absorption spectroscopy, atomic fluorescence spectrometry, and atomic emission spectrometry are also widely used and covered in this review together with some less utilised techniques. This journal i

An evaluation of extraction techniques for arsenic in staple diets (fish and rice) utilising both classical and enzymatic extraction methods

Enzymatic extraction methods were evaluated with classical extraction approaches for the determination of arsenic in food. The extraction efficiency for total arsenic was determined by analysing CRM materials DORM-3 fish protein, NIES 106 rice flour and GBW10015 spinach. These were compared with total arsenic concentration determined using microwave-assisted acid digestion and ICP-MS. The total arsenic concentrations in the CRM materials were in good agreement with the certified values. Enzymatic hydrolysis using trypsin has been successfully employed to extract arsenic species in DORM-3 and fish samples. Whilst this method of hydrolysing the proteins worked well for the fish samples, an alternative approach was required to facilitate the digestion of cellulose in plant materials. However, enzymatic extraction using cellulase was found to give unsatisfactory results for both the NIES and GBW10015 CRM materials. Dilute nitric acid (1% HNO3) was found to give a more efficient extraction for arsenic species in the same CRM materials and rice samples. The study was extended to evaluate a range of real samples. Total arsenic concentrations in 13 different types of fish tissue were determined following microwave-assisted acid digestion using nitric acid/hydrogen peroxide, followed by measurement using HPLC-ICP-MS for speciation analysis. The results obtained for fish were in the range of 3.53–98.80 µg g−1 As (dry weight). Similarly, the results of 17 rice samples were in the range of 0.054–0.823 µg g−1. This study demonstrates the importance of selecting an appropriate extraction technique for the quantitative measurement of arsenic species in food

Measuring cis-acting regulatory variants genome-wide: new insights into expression genetics and disease susceptibility

A recent large-scale allelic expression analysis shows that cis-acting regulatory variants might reveal some of the 'missing heritability' component of complex disorders, which could lead to potential therapy and prevention breakthroughs

Context, ethics and pharmacogenetics

Most of the literature on pharmacogenetics assumes that the main problems in implementing the technology will be institutional ones (due to funding or regulation) and that although it involves genetic testing, the ethical issues involved in pharmacogenetics are different from, even less than, 'traditional' genetic testing. Very little attention has been paid to how clinicians will accept this technology, their attitudes towards it and how it will affect clinical practice. This paper presents results from interviews with clinicians who are beginning to use pharmacogenetics and explores how they view the ethics of pharmacogenetic testing, its use to exclude some patients from treatment, and how this kind of testing fits into broader debates around genetics. In particular this paper examines the attitudes of breast cancer and Alzheimer's disease specialists. The results of these interviews will be compared with the picture of pharmacogenetics painted in the published literature, as a way of rooting this somewhat speculative writing in clinical practice

Synaptic Signaling and Aberrant RNA Splicing in Autism Spectrum Disorders

Interactions between presynaptic and postsynaptic cellular adhesion molecules (CAMs) drive synapse maturation during development. These trans-synaptic interactions are regulated by alternative splicing of CAM RNAs, which ultimately determines neurotransmitter phenotype. The diverse assortment of RNAs produced by alternative splicing generates countless protein isoforms necessary for guiding specialized cell-to-cell connectivity. Failure to generate the appropriate synaptic adhesion proteins is associated with disrupted glutamatergic and gamma-aminobutyric acid signaling, resulting in loss of activity-dependent neuronal plasticity, and risk for developmental disorders, including autism. While the majority of genetic mutations currently linked to autism are rare variants that change the protein-coding sequence of synaptic candidate genes, regulatory polymorphisms affecting constitutive and alternative splicing have emerged as risk factors in numerous other diseases, accounting for an estimated 40–60% of general disease risk. Here, we review the relationship between aberrant RNA splicing of synapse-related genes and autism spectrum disorders

Determination of essential and trace elements in various vegetables using ICP-MS

المحتويات المعدنية في الخضراوات مثيرة للاهتمام بسبب المشكلات المتعلقة بسلامة الأغذية والمخاطر الصحية ‏المحتملة.. توفير هذه المعادن في جسم الإنسان قد يؤدي العديد من الوظائف البيوكيميائية ‏وبعضها مرتبط بأمراض مختلفة عند ‏مستويات عالية. الدراسة الحالية استهدفت إلى ايجاد تركيز المعادن المختلفة في الخضروات المحلية الشائعة المستهلكة ‏باستخدام مطياف كتلة البلازما المقترنة بالحث ICP-MS. اظهرت الدراسة الحالية أن تراكيز المعادن في خضراوات الطرخون، ورق الغار، الباي، والشبت، والمسكيت السوري، وورق العنب، والزعتر، والجرجير، والريحان، والرجلة الشائعة، والبقدونس كان يتراوح في حدود ل ‏10-778 مع Al، لـ 333-10 معB ، لـ 4-1194 معBa ، لـ 24645-2812 مع Ca ، لـ 0.1-0.32 مع Co، لـ 201-464 مع Fe، لـ 3661-46400 مع K، لـ1.53-0.31  مع Li ، لـ 860-14330 مع  Mg، لـ 16.20-71.5 مع Mn، لـ 612-4725 مع Na، لـ 15.8-46 مع Zn ميكروغرام\ غرام. أظهرت النتائج أن تركيز Al، B باستثناء المسكيت السوري،Ba ، Ca،Fe ،K ،Mg ، Mn في جميع الخضروات التي تم تحليلها أعلى من القيمة الموصى بها، Li في حدود الحد الآمن وCo ، Na باستثناء الشبت والجرجير والرجلة الشائعة، والزنك أقل من المدخول الموصى به من هذه العناصر. من وجهة النظر الصحية، تم استخدام المقدار اليومي المقدر(‏EDI‏)، وحاصل المخاطر(‏HQ‏) ومؤشر ‏المخاطر(‏HI‏) من المعادن الثقيلة لتقدير تقييم المخاطر الصحية المرتبطة باستهلاك هذه الخضروات كانت قيم HQ لـ Al و Fe (لجميع الخضروات) و Ba (في الشبت وأوراق العنب والزعتر والجرجير والريحان والرجلة الشائعة والبقدونس) أعلى من واحد، مما يشير إلى احتمالية التعرض  الخطرالصحى غير سرطانية بسبب التعرض لهذه المعادن. علاوة على ذلك ، كانت قيمة HI لجميع الخضروات أعلى من واحد، مما يشير إلى مخاطر صحية غير سرطانية محتملة بسبب التعرض الطويل الأمد لهذه المعادن.Metal contents in vegetables are interesting because of issues related to food safety and ‎potential health risks. The availability of these metals in the human body ‎may perform many biochemical functions and some of them linked with various diseases at ‎high levels. The current study aimed to evaluate the concentration of various metals in ‎common local consumed vegetables using ICP-MS. The concentrations of metals in vegetables ‎of tarragon, Bay laurel, dill, Syrian mesquite, vine leaves, thymes, arugula, basil, common ‎purslane and parsley of this study were found to be in the range of, 76-778 for Al, 10-333 for B, 4-119 for ‎Ba, ‎2812‎-24645 for Ca, 0.1-0.32 for Co, 201-464 for Fe, 3661-46400 for K, 0.31–‎‎1.53 for Li, 860-14330 for Mg, 16.20-71.5 for Mn, 612-4725 for Na and 15.8-46 µg ‎g-1 for Zn. The results revealed that the concentration of Al, B except in Syrian mesquite, Ba, Ca, ‎Fe, K, Mg and Mn in all analysed vegetables is higher than the recommended value, Li is ‎well-within the safe limit, and Co, Na except in dill, arugula and common purslane, Zn are ‎lower than the recommended intake of these elements. From health point of view, the HQ values for Al, Fe ‎‎(for all vegetables) and Ba (in dill, vine leaves, thymes, arugula, basil, common ‎‎purslane and ‎parsley) were higher than one, indicating potential non-cancer health risk due to exposure to ‎these metals. Furthermore, the HI value for all vegetables was higher than one, indicating ‎potential non-cancer health risk due to long-term exposure to these metals

SLC15A2 genomic variation is associated with the extraordinary response of sorafenib treatment: whole-genome analysis in patients with hepatocellular carcinoma

Reliable biomarkers are required to predict the response to sorafenib. We investigated genomic variations associated with responsiveness to sorafenib for patients with unresectable hepatocellular carcinoma (HCC). Blood samples from 2 extreme, 2 strong and 3 poor responders to sorafenib were subjected to whole-genome analysis. Then, we validated candidate genomic variations with another 174 HCC patients, and performed in vitro functional analysis and in silico analyses. Genomic data of > 96 gigabases/sample was generated at average of similar to 34X sequencing depth. In total, 1813 genomic variations were matched to sorafenib responses in clinical data; 708 were located within regions for sorafenib-target genes or drug absorption, distribution, metabolism, and excretion (ADME)-related genes. From them, 36 variants were within the coding regions and 6 identified as non-synonymous single-nucleotide variants from 4 ADME-related genes (ABCB1, FMO3, MUSK, and SLC15A2). Validation genotyping confirmed sequencing results and revealed patients genotype for rs2257212 in SLC15A2 showed longer progression-free survival (HR = 2.18). In vitro study displayed different response to sorafenib depending on the genotype of SLC15A2. Structural prediction analysis revealed changes of the phosphorylation levels in protein, potentially affecting sorafenib-associated enzymatic activity. Our finding using extreme responder seems to generate robust biomarker to predict the response of sorafenib treatment for HCCopen0

Genetic association analysis of N-methyl-d-aspartate receptor subunit gene GRIN2B and clinical response to clozapine

OBJECTIVE: Approximately 30% of patients with schizophrenia fail to respond to antipsychotic therapy and are classified as having treatment-resistant schizophrenia. Clozapine is the most efficacious drug for treatment-resistant schizophrenia and may deliver superior therapeutic effects partly by modulating glutamate neurotransmission. Response to clozapine is highly variable and may depend on genetic factors as indicated by twin studies. We investigated eight polymorphisms in the N-methyl-d-aspartate glutamate receptor subunit gene GRIN2B with response to clozapine. METHODS: GRIN2B variants were genotyped using standard TaqMan procedures in 175 European patients with schizophrenia deemed resistant or intolerant to treatment. Response was assessed using change in Brief Psychiatric Rating Scale scores following six months of clozapine therapy. Categorical and continuous response was assessed using chi-squared test and analysis of covariance, respectively. RESULTS: No associations were observed between the variants and response to clozapine. A-allele carriers of rs1072388 responded marginally better to clozapine therapy than GG-homozygotes; however, the difference was not statistically significant (p = 0.067, uncorrected). CONCLUSIONS: Our findings do not support a role for these GRIN2B variants in altering response to clozapine in our sample. Investigation of additional glutamate variants in clozapine response is warranted. Copyright © 2016 John Wiley & Sons, Ltd

Total arsenic and arsenic speciation in indigenous food stuffs

The properties of an element are highly dependent on its chemical form, it’s called elemental speciation. This study evaluates the arsenic species found in a range of food stuffs together with growing environments and toxicity issues. Total arsenic concentrations in fish tissue and vegetable crops were determined by ICP-MS following microwave-assisted acid digestion using nitric acid/hydrogen peroxide, trypsin and cellulase enzymatic extraction procedures. The extracted arsenic species were then quantified using HPLC-ICP-MS. A dilute nitric acid (1 % (v/v)) digestion procedure was also used to extract arsenic species from rice and the different parts (root, skin, stem, leaf and grain) of a range of plant crops. The study was extended to include the aqua-regia extractable arsenic content of the soils collected from the area where the plants had been cultivated in the Kurdistan region of Iraq. Irrigation water was also investigated, but found to contain low levels of arsenic. An anion-exchange HPLC-ICP-MS method was developed, using sulphate and phosphate, for the separation and quantification of AsB, MMA, DMA, InAsIII and InAsV. The results obtained for fish samples were in the range of 3.53-98.80 µg g-1 (dry weight) with non-toxic AsB being the predominant species. The InAsV concentration was in the range of 0.1-1.19 µg g-1 for all fish species except for the John Dory which was below the limit of detection (0.027 µg g-1). Total arsenic, arsenic species, and total multi-elements (including Ag, Al, B, Ba, Be, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Sb, Se, Si, Ti, V and Zn) were determined in rice samples from Kurdistan, Iraq and other regions of geographical origin. The transport of arsenic from the soil and irrigation water into roots, stem, leaf and subsequently into the grain or bean of the plants is important when assessing the potential health risks from food crops. For the soil sample, InAsV was found to be the major species with smaller quantities of InAsIII . After applying a full BCR sequential extraction procedure to the soils, it was found that 7.87 - 21.14 % of the total arsenic was present in an easily acid-soluble extractable form. Finally, a novel method was developed to measure total arsenic and arsenic species associated with vegetative DNA. In rice plant, it was found that InAsV incorporated within the DNA molecule in which it could replace phosphate. It was also found that the concentration of InAsV associated with DNA molecule decreased with decreasing total arsenic in the rice plant from the root to the leaf.Ministry of Higher Education and Scientific Research-Kurdistan region of Ira