| 1. |
- Havarinasab, Said, et al.
(author)
-
Dose-response study of thimerosal-induced murine systemic autoimmunity
- 2004
-
In: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X. ; 194:2, s. 169-179
-
Journal article (peer-reviewed)abstract
- The organic compound ethylmercurithiosalicylate (thimerosal), which is primarily present in the tissues as ethylmercury, has caused illness and several deaths due to erroneous handling when used as a disinfectant or as a preservative in medical preparations. Lately, possible health effects of thimerosal in childhood vaccines have been much discussed. Thimerosal is a well-known sensitizing agent, although usually of no clinical relevance. In rare cases, thimerosal has caused systemic immune reactions including acrodynia. We have studied if thimerosal might induce the systemic autoimmune condition observed in genetically susceptible mice after exposure to inorganic mercury. A.SW mice were exposed to 1.25–40 mg thimerosal/l drinking water for 70 days. Antinucleolar antibodies, targeting the 34-kDa protein fibrillarin, developed in a dose-related pattern and first appeared after 10 days in the two highest dose groups. The lowest observed adverse effect level (LOAEL) for antifibrillarin antibodies was 2.5 mg thimerosal/l, corresponding to an absorbed dose of 147 μg Hg/kg bw and a concentration of 21 and 1.9 μg Hg/g in the kidney and lymph nodes, respectively. The same LOAEL was found for tissue immune-complex deposits. The total serum concentration of IgE, IgG1, and IgG2a showed a significant dose-related increase in thimerosal-treated mice, with a LOAEL of 5 mg thimerosal/l for IgG1 and IgE, and 20 mg thimerosal/l for IgG2a. The polyclonal B-cell activation showed a significant dose–response relationship with a LOAEL of 10 mg thimerosal/l. Therefore, thimerosal induces in genetically susceptible mice a systemic autoimmune syndrome very similar to that seen after treatment with inorganic mercury, although a higher absorbed dose of Hg is needed using thimerosal. The autoimmune syndrome induced by thimerosal is different from the weaker and more restricted autoimmune reaction observed after treatment with an equipotent dose of methylmercury.
|
|
| 2. |
- Majidi, Vahid, et al.
(author)
-
Improving sensitivity for CE-ICP-MS using multicapillary parallel separation
- 1999
-
In: Journal of Analytical Atomic Spectrometry. - : Royal Society of Chemistry (RSC). - 0267-9477 .- 1364-5544. ; 14:12, s. 1933-1935
-
Journal article (peer-reviewed)abstract
- A multicapillary, capillary electrophoresis inductively coupled plasma mass spectrometry interface is described. This interface allows for higher sample loading to improve the overall sensitivity and analyte detection limits without sacrificing the separation efficiencies. The results obtained with this parallel system are presented for a cross flow nebulizer. A comparison of single capillary electrophoresis for both DIHEN and cross flow nebulizers is presented.
|
|
| 3. |
- Qvarnström, Johanna, et al.
(author)
-
Determination of methylmercury, ethylmercury, and inorganic mercury in mouse tissues, following administration of thimerosal, by species-specific isotope dilution GC-inductively coupled plasma-MS
- 2003
-
In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 75:16, s. 4120-4124
-
Journal article (peer-reviewed)abstract
- Isotopically enriched HgO standards were used to synthesize CH 3200Hg+ and C2H5199Hg+ using Grignard re-agents. These species were employed for isotope dilution GC-ICPMS to study uptake and biotransformation of ethylmercury in mice treated with thimerosal, (sodium ethylmercurithiosalicylate) 10 mg L-1 in drinking water ad libitum for 1, 2.5, 6, or 14 days. Prior to analysis, samples were spiked with aqueous solutions of CH3200Hg+, C2H 5199Hg+, and 201Hg2+ and then digested in 20% tetramethylammonium hydroxide and extracted at pH 9 with DDTC/toluene. Extracted mercury species were reacted with butylmagnesium chloride to form butylated derivatives. Absolute detection limits for CH 3Hg+, C2H5Hg+, and Hg2+ were 0.4, 0.2, and 0.6 pg on the basis of 3s of five separate blanks. Up to 9% of the C2H5Hg+ was decomposed to Hg2+ during sample preparation, and it is therefore crucial to use a species-specific internal standard when determining ethylmercury. No demethylation, methylation, or ethylation during sample preparation was detected. The ethylmercury component of thimerosal was rapidly taken up in the organs of the mice (kidney, liver, and mesenterial lymph nodes), and concentrations of C2H5Hg+ as well as Hg2+ increased over the 14 days of thimerosal treatment. This shows that C2H5Hg+ in mice to a large degree is degraded to Hg2+. Increased concentrations of CH3Hg + were also observed, which was found to be due to impurities in the thimerosal.
|
|
| 4. |
- Qvarnström, Johanna, et al.
(author)
-
Mercury species transformations during sample pre-treatment of biological tissues studied by HPLC-ICP-MS
- 2002
-
In: Journal of Analytical Atomic Spectrometry. - : RSC Publishing. - 0267-9477 .- 1364-5544. ; 17:11, s. 1486-1491
-
Journal article (peer-reviewed)abstract
- A high-performance liquid chromatography (HPLC) system with a C18 column and an aqueous phase eluent (0.08% ammonium acetate and 0.02% L-cysteine) was directly connected to an inductively coupled plasma mass spectrometer (ICP-MS). HPLC-ICP-MS was used to study the abiotic formation of methylmercury, CH3Hg+, from inorganic mercury, Hg2+, as well as demethylation of CH3Hg+ to Hg2+ in biological tissues during treatment with tetramethylammonium hydroxide (TMAH) followed by pH adjustment with citric or acetic acid. Enriched isotope standards from CH3198Hg+ and 201Hg2+ were added to the samples to monitor species transformation and to apply species-specific isotope dilution (SSID) calibration. Depending on the type of sample matrix, up to 11.5% of added Hg2+ was methylated and up to 6.26% CH3Hg+ was demethylated to Hg2+. Methylation of Hg2+ probably takes place mainly during and after pH adjustment and it decreases after prolonged TMAH treatment. To minimize abiotic methylation, it is therefore recommended to proceed with pH adjustment after samples have been treated with TMAH for 24 h. There is no significant difference in the degree of methylation using citric or acetic acid.
|
|
| 5. |
- Qvarnström, Johanna, 1974-
(author)
-
On the reliability of methods for the speciation of mercury based on chromatographic separation coupled to atomic spectrometric detection
- 2003
-
Doctoral thesis (other academic/artistic)abstract
- This thesis deals with the reliability of methods for the speciation of mercury in environmental and biological samples. Problems with speciation methods that couple chromatography to atomic spectrometric detection and how to overcome the problems are discussed. Analytical techniques primarily studied and evaluated are high performance liquid chromatography-cold vapour-atomic absorption spectrometry (HPLC-CV-AAS), HPLC-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS), capillary electrophoresis-ICP-MS (CE-ICP-MS) and gas chromatography-ICP-MS (GC-ICP-MS). Applying a multi-capillary approach increased the analyte amount injected into a CE-ICP-MS system and improved the overall sensitivity. A microconcentric nebulizer with a cyclone spray chamber was shown to improve the detection limits for mercury species 3-13 times in HPLC-ICP-MS and 11-19 times in CE-ICP-MS compared to a cross-flow nebulizer with a Scott spray chamber. To decrease the interference of water vapour in HPLC-CV-AAS a Nafion dryer tube was inserted between the CV-generation and the detector. Methyl mercury was however lost in the Nafion unless it was reduced to elemental mercury prior transport through the dryer tube. During sample pre-treatment, incomplete extraction, losses and transformation (alkylation, dealkylation, oxidation and reduction) of mercury species can lead to significant errors (underestimation and overestimation) in the determination of the concentrations. Methods to detect and determine the degree of transformation as well as correct for errors caused by transformation are presented in the thesis. The preferable method use species-specific enriched stable isotope standards in combination with MS detection and a matrix based calculation scheme. This approach is very powerful as both the concentrations of the species as well as the degrees of transformation can be determined within each individual sample.
|
|
| 6. |
- Snell, James P., et al.
(author)
-
Preparation and certification of ERM-AE670, a 202Hg enriched methylmercury isotopic reference material
- 2004
-
In: JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY. - : Royal Society of Chemistry (RSC). - 0267-9477. ; 19:10, s. 1315-24
-
Journal article (peer-reviewed)abstract
- The need for comparability of methylmercury, noted MeHg, measurement results and for the reduction of their associated uncertainties is hampered by the lack of suitable calibration materials. An isotopic certified reference material, ICRM, of MeHg containing isotopically enriched Hg has the potential to answer these problems, in combination with the isotope dilution mass spectrometry, IDMS, strategy. The objective of this work was to produce such a material, of demonstrated stability and carrying certified values traceable to the SI accompanied by combined uncertainty statements. Mercury oxide enriched in 202Hg was used for the preparation of a solution of 202Hg enriched CH3HgCl. The starting material had previously been employed for the preparation of ERM-AE640; a 202Hg enriched inorganic mercury ICRM. The CH3HgCl was synthesised by reaction with a Grignard reagent and a subsequent comproportionation reaction between (CH3)2Hg and HgCl2. The process was optimised to give a high yield of the product, minimise contamination with naturalHg and additional steps were applied to purify the material from other Hg species and by-products of the synthesis reaction. Aliquots of 5 g of the solution were sealed in quartz ampoules for later distribution as a reference material, named ERM-AE670. Using gas chromatography inductively coupled plasma mass spectrometry, only MeHg and inorganic Hg was detectable in the finished reference material with inorganic Hg in <2% of the total amount. The isotopic composition of Hg in the form of MeHg was confirmed to be identical to that of ERM-AE640, within enlarged uncertainty statements. The Hg amount content in the form of MeHg was obtained by subtraction of the inorganic Hg amount content from the total Hg amount content (determined by IDMS in the digested material). The final uncertainty on the Hg amount content in the form of MeHg (3.5% relative, k= 2) included a contribution covering for potential changes over 2 years of shelf-life. This contribution was estimated from the results of a 1 year isochronous stability study.
|
|
| 7. |
- Srivastava, Vaibhav, et al.
(author)
-
OnPLS integration of transcriptomic, proteomic and metabolomic data shows multi-level oxidative stress responses in the cambium of transgenic hipI- superoxide dismutase Populus plants
- 2013
-
In: BMC Genomics. - : BioMed Central. - 1471-2164. ; 14
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Reactive oxygen species (ROS) are involved in the regulation of diverse physiological processes in plants, including various biotic and abiotic stress responses. Thus, oxidative stress tolerance mechanisms in plants are complex, and diverse responses at multiple levels need to be characterized in order to understand them. Here we present system responses to oxidative stress in Populus by integrating data from analyses of the cambial region of wild-type controls and plants expressing high-isoelectric-point superoxide dismutase (hipI-SOD) transcripts in antisense orientation showing a higher production of superoxide. The cambium, a thin cell layer, generates cells that differentiate to form either phloem or xylem and is hypothesized to be a major reason for phenotypic perturbations in the transgenic plants. Data from multiple platforms including transcriptomics (microarray analysis), proteomics (UPLC/QTOF-MS), and metabolomics (GC-TOF/MS, UPLC/MS, and UHPLC-LTQ/MS) were integrated using the most recent development of orthogonal projections to latent structures called OnPLS. OnPLS is a symmetrical multi-block method that does not depend on the order of analysis when more than two blocks are analysed. Significantly affected genes, proteins and metabolites were then visualized in painted pathway diagrams.RESULTS: The main categories that appear to be significantly influenced in the transgenic plants were pathways related to redox regulation, carbon metabolism and protein degradation, e.g. the glycolysis and pentose phosphate pathways (PPP). The results provide system-level information on ROS metabolism and responses to oxidative stress, and indicate that some initial responses to oxidative stress may share common pathways.CONCLUSION: The proposed data evaluation strategy shows an efficient way of compiling complex, multi-platform datasets to obtain significant biological information.
|
|
| 8. |
- Tu, Qiang, et al.
(author)
-
Determination of mercury species by capillary zone electrophoresis-inductively coupled plasma mass spectrometry: a comparison of two spray chamber-nebulizer combinations
- 2000
-
In: ANALYST. - : Royal Society of Chemistry (RSC). ; 125:4, s. 705-710
-
Journal article (peer-reviewed)abstract
- A method based on capillary zone electrophoresis (CZE) separation and inductively coupled plasma mass spectrometry (ICP-MS) detection is presented for the determination of methylmercury and inorganic mercury. The CZE conditions were optimised with respect to the flow rates for nebulizer gas and sheath solution, concentration of electrolyte and applied voltage. The performances of two different sample injection systems were compared. A standard cross-flow nebulizer with a Scott spray chamber offered a shorter analysis time, better resolution and ruggedness, while a micro-concentric nebulizer (MCN-100) with a cyclone spray chamber improved the detection limit by a factor of 11 for CH3Hg+ and a factor of 19 for Hg2+. With the MCN-100,the detection limits were 13.6 ng ml(-1) for CH3Hg+ and 6.0 ng ml(-1) for Hg2+, corresponding to absolute detection limits of 2.3 pg and 1.0 pg, respectively, for a hydrodynamic injection of 170 nl. The method was tested using three biological certified reference materials with a certified methylmercury content. The pre-treatment of biological samples involves only digestion and pH adjustment, without the need for derivatization or extraction, so that potential errors involved in these usually time-consuming steps can be avoided.
|
|
