Clinical Toxicity of Nickel

In this work, I have measured the concentration of Ni in human albumin solutions used for intravenous administration, which have been produced by different manufacturers, at different times. Additional results for the concentrations of other metals, at various stages of the production process, were also obtained using multielement semiquantitative scanning by inductively coupled plasma-mass spectrometry (ICP-MS) (Chapter 2). In the last ten years, increasing efforts have been made to limit the contamination of dialysis fluids with metals, present in water, salts and haemodialysis equipment. This was intended to eliminate aluminium toxicity and may have incidentally also reduced Ni contamination. Results for Ni concentrations in the serum of haemodiaiysed patients are limited and sometimes contradictory, compared to the vast literature on serum aluminium concentrations. The assessment of Ni concentrations has proven more difficult, due to problem of pre-anaiytical contamination and the lower concentrations present. In Chapter 2 I report an investigation of the serum Ni concentrations in a group of patients undergoing regular haemodialysis and the effect a single dialysis treatment has on serum Ni concentrations in the same subjects. The understanding of the toxicology of Ni at low doses will benefit from improved knowledge of Ni biochemistry and metabolic pathways. Several studies have been carried out to investigate the metabolism of Ni in man (Nodiya, 1972; Cronin et al., 1980; Solomons et al., 1982; Gawkrodger et al., 1986; Sunderman et al., 1989) but only two report data on faecal excretion (Nodiya, 1972; Sunderman et al., 1989). There was a large inter-individual variability in the estimates of Ni absorption and excretion. In all the experiments, volunteers ingested Ni, as the naturally occurring mixture of five isotopes, and results could be affected by the contribution of Ni from diet and contamination of samples prior to analysis. Nickel metabolism has been studied in rats and rabbits using radioisotopes (63Ni, 57Ni) (Onkelinx et al., 1973; Nielsen et al., 1993) but limitations of radiation dosage prevent the application of this technique in man. The recent development of ICP-MS, which can provide information on the isotopic composition of an element using simplified procedures, offers the opportunity to apply stable isotopes for the study of mineral metabolism in humans on a larger scale. Different separation procedures were used to remove the mass interferences affecting the determination of the minor Ni isotopes in human albumin solutions, blood, erythrocytes, urine, faeces and tissues. A method was developed, that allowed the determination of three out of five Ni isotopes, one of which was used for isotopic dilution (Chapter 3). Nickel metabolism was investigated in four volunteers, who ingested a single dose of as a tracer. Nickel absorption, distribution and excretion were determined by analysing plasma, urine and faeces, collected at various time intervals for up to five days (Chapter 4). The role of Ni in the human environment and the present knowledge on its biochemistry, metabolism, health effects and analytical methods of determination are summarised in Chapter 1. (Abstract shortened by ProQuest.)

Atomic spectrometry update. Clinical and biological materials, foods and beverages

This review discusses developments in elemental mass spectrometry, atomic absorption, emission and fluorescence, XRF and LIBS, as applied to the analysis of specimens of clinical interest, foods and beverages. Sample preparation procedures and quality assurance are also included.</p

Estimate of Uncertainty of Measurement from a Single-Laboratory Validation Study: Application to the Determination of Lead in Blood

Abstract Background: Lead is an environmental pollutant, and human exposure is assessed by monitoring lead concentrations in blood. Because the main source of environmental exposure has been the use of leaded gasoline, its phase-out has led to decreased lead concentrations in the general population. Therefore, validated analytical methods for the determination of lower lead concentrations in blood (&lt;150 μg/L) are needed. In addition, new ISO standards require that laboratories determine and specify the uncertainty of their results. Methods: We validated a method to determine lead in blood at concentrations up to 150 μg/L by electrothermal atomic absorption spectrometry with Zeeman background correction according to EURACHEM guidelines. Blood samples were diluted (1:1 by volume) with 2 mL/L Triton X-100. NH4H2PO4 (5 g/L) and Mg(NO3)2 (0.5 g/L) were used as modifiers. Matrix-matched standards were used for calibration. Results: We determined the limits of detection (3.1 μg/L) and quantification (9.4 μg/L). Repeatability and intermediate imprecision within the range 35–150 μg/L were &lt;5.5% and &lt;6.0%, respectively. We assessed trueness by use of certified reference materials, by recovery tests, and by comparison with target values of other reference materials (candidate external quality assessment samples). The expanded uncertainty ranged from 20% to 16% (with a confidence level of 95%) depending on concentration. Conclusions: This study provides a working example of the estimate of uncertainty from method performance data according to the EURACHEM/CITAC guidelines. The estimated uncertainty is compatible with quality specifications for the analysis of lead in blood adopted in the US and the European Union

Plexo coroideu: local de síntese de hormonas esteróides?

O plexo coroideu (CP), uma estrutura altamente vascularizada, encontra-se dentro dos ventrículos do cérebro e é composto por vilosidades enroladas aos capilares, tecido conjuntivo e uma monocamada de células epiteliais ciliadas. O CP produz o líquido cefalorraquidiano (LCR) que mantém o meio extracelular do cérebro e forma uma interface única entre o sangue e o LCR. A biossíntese de esteroides ocorre na glândula adrenal, nas gónadas e no cérebro – neuroesteroides. Um trabalho desenvolvido anteriormente permitiu identificar várias enzimas da via esteroidogénica, pertencentes à família do citocromo P450 (CYP), hidroxiesteroide desidrogenase (HSD) e redutase, no CP de rato, através da análise de microarrays de cDNA. Portanto, o objetivo deste estudo foi confirmar e analisar a expressão do citocromo P450, família 11, subfamília a, polipéptido 1 (CYP11A1), citocromo P450, família 11, subfamília b, polipéptido 3 (CYP11B3), citocromo P450, família 17, subfamília a, polipéptido 1 (CYP17A1), 17β-hidroxiesteroide desidrogenase (17β-HSD), 5α-redutase (ST5ared) e citocromo P450, família 19, subfamília a, polipéptido 1 (CYP19A1) no CP de Rattus norvegicus e Sus domesticus. Assim, os níveis de expressão de mRNA destas enzimas foram analisados por RT-PCR e PCR em tempo real, enquanto os níveis proteicos foram analisados por imunocitoquímica e imunohistoquímica. Por fim, foi testada a funcionalidade destas enzimas em culturas ex vivo usando percursores tritiados da via esteroidogénica. Este trabalho permitiu-nos confirmar a expressão destas enzimas e determinar a sua localização nas células epiteliais do CP de rato e no CP de porco. Para além disso, os ensaios ex vivo mostraram que há síntese de hormonas esteroides a partir de percursores tritiados nos explantes de CP.The choroid plexus (CP), a highly vascularized structure, lies within the ventricles of the brain and is composed by convoluted villi with capillaries, connective tissue and a monolayer of ciliated epithelial cells. CP produces the cerebrospinal fluid (CSF) that maintains the extracellular milieu of the brain and form a unique interface between the peripheral blood and the CSF. Steroid biosynthesis occurs in the adrenal gland, in the gonads and, in the brainneurosteroids. In previous work found that several enzymes of the steroidogenic pathway, which belong to the family of cytochrome P450 (CYP), hydroxysteroid dehydrogenase (HSD) and reductase are expressed in CP by cDNA microarray analysis. So, the aim of this study was to confirm and analyse the expression of cytochrome P450, family 11, subfamily a, polypeptide 1 (CYP11A1), cytochrome P450, family 11, subfamily b, polypeptide 3 (CYP11B3), cytochrome P450, family 17, subfamily a, polypeptide 1 (CYP17A1), hydroxysteroid (17-β) dehydrogenase 8 (17β-HSD8), steroid-5-α-reductase (ST5ared) and cytochrome P450, family 19, subfamily a, polypeptide a (CYP19A1) in CP of Rattus norvegicus and Sus domesticus. mRNA expression levels of these enzymes were evaluated by RT-PCR and Real-time PCR, while protein levels were evaluated by immunocytochemistry and immunohistochemistry. Finally, we tested the functionality of these enzymes ex-vivo using tritiated percursors of the steroidogenic pathway. We were able to confirm the expression of these enzymes and determine their location in CP epithelial cells of rat and pig CP. Moreover, ex-vivo assays showed that steroid hormones synthesis from tritiated precursors occurs in CP explants

TrainMiC® Presentations Translated in Albanian

TrainMiC® is a European programme for life-long learning about how to interpret the metrological requirements in chemistry. It is operational across many parts of Europe via national teams. These teams use shareware pedagogic tools which have been harmonized at European level by a joint effort of many experts across Europe working in an editorial board. The material has been translated into fourteen different languages. In this publication, TrainMiC® presentations translated in Albanian language by the Albanian TrainMiC® team are published.JRC.D.3-Knowledge Transfer and Standards for Securit

TrainMiC® Presentations Translated in Serbian

TrainMiC® is a European programme for life-long learning about how to interpret the metrological requirements in chemistry. It is operational across many parts of Europe via national teams. These teams use shareware pedagogic tools which have been harmonized at European level by a joint effort of many experts across Europe working in an editorial board. The material has been translated into fourteen different languages. In this publication, TrainMiC® presentations translated in Serbian language by the Serbian TrainMiC® team are published.JRC.D.3-Knowledge Transfer and Standards for Securit

TrainMiC® Presentations Translated in Spanish

TrainMiC® is a European programme for life-long learning about how to interpret the metrological requirements in chemistry. It is operational across many parts of Europe via national teams. These teams use shareware pedagogic tools which have been harmonized at European level by a joint effort of many experts across Europe working in an editorial board. The material has been translated into fourteen different languages. In this publication, TrainMiC® presentations translated in Spanish language by the Spanish TrainMiC® team are published.JRC.D.3-Knowledge Transfer and Standards for Securit

TrainMiC® Presentations Translated in Portuguese

TrainMiC® is a European programme for life-long learning about how to interpret the metrological requirements in chemistry. It is operational across many parts of Europe via national teams. These teams use shareware pedagogic tools which have been harmonized at European level by a joint effort of many experts across Europe working in an editorial board. The material has been translated into fourteen different languages. In this publication, TrainMiC® presentations translated in Portuguese language by the Portuguese TrainMiC® team are published.JRC.D.3-Knowledge Transfer and Standards for Securit