High resolution inductively coupled plasma mass spectrometry: Some applications in biomedicine
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- Institutt for kjemi 
Even though trace elements are present at minute amounts in the human body, they have a considerable impact on human health, either as essential elements in biochemical functions indispensable for life, or on the contrary, interfering with vital processes. Knowledge of the optimal concentrations of trace elements in the human body is therefore of great importance. Since the first systematic determinations of trace elements in human body fluids started in the 1940s there has been an incredible development in analytical instrumentation. The objective of this thesis is to demonstrate successful applications of HR-ICP-MS (high resolution inductively coupled plasma mass spectrometry) in biomedicine. Research on trace elements in humans is challenging because of very low levels and many different types of matrices. The first important issue regarding trace element analysis is sampling and sample storage. It is essential to control all possible sources of contamination and other factors that can influence the concentrations. Preservation of biological samples is often required, and effects of the frequently used preservation and storage of biological tissue in formalin have been examined in this work. The concentrations of 20 trace elements were determined in formalin where brain samples had been stored at different time intervals ranging from few weeks to several years. The results show that storage of biological tissue in formalin may result in losses of trace elements from the tissue to the formalin, and that the leakage is time-dependent. This emphasizes the importance of controlling all steps from sample collection to analysis. With its low detection limits, high resolution and multielement capability, HR-ICP-MS offers a considerable potential for further understanding the role of trace elements in biological material. These features were used to develop a method to study protein-bound metals in cerebrospinal fluid (CSF). CSF samples from eight healthy persons were separated by size exclusion HPLC and the resulting fractions were analyzed using HR-ICPMS. The major challenge in this work was the very low concentrations as only 100 μl CSF was injected to the column resulting in 35 fractions of 0.75 ml. It was possible to determine more than 10 elements of clinical interest in the CSF fractions and the method provides an opportunity to study MT and other metal binding proteins in CSF. Further, the potential to study exposure and intake of trace elements by HRICP- MS was explored by analyzing hair strands of five occupationally unexposed subjects. The trace element profiles of single hair strands were determined by analyzing 1 cm long segments. The challenge in this study was again the extremely small sample size, as the samples had an average weight of 0.05 mg. It was possible however to obtain results for 12 elements in these minute samples and valuable information about intake and exposure for Hg, Se and Sr was obtained. HR-ICP-MS has the potential to be an excellent tool for obtaining information about disease development and progress. A rare and relatively unexplored neurodegenerative disease (Skogholt’s disease) was studied. The trace element concentrations in whole blood, plasma and CSF were determined in Skogholt patients, multiple sclerosis patients and controls. Increased levels of Cu, Fe, Zn, Se and S in CSF were found in CSF from Skogholt patients. These increased levels were not reflected in blood, and it is quite obvious that the increased levels are not caused by increased environmental exposure. The results suggest that the increased levels of these elements in CSF are due to a leakage of metal binding proteins from blood to the CSF. Trace elements have been implicated in the development of Parkinson’s disease (PD), and a study was performed on trace elements in serum from Parkinson patients collected in 1995-97, 4-12 years before they were diagnosed with the disease. New samples from more than half of these patients were collected in 2007. No significant differences were found between preclinical levels and controls, except for a lower level of Hg in the patient group. However, when trace element serum levels in patients from before and after they were diagnosed were compared, significant differences for several elements were found. This suggests that trace element imbalances found in PD patients may be a result of disease development rather than a causal factor. HR-ICP-MS offers a considerable potential for further understanding the role of trace elements in humans. Biological material is often available for analysis only in small amounts. HR-ICP-MS gives the opportunity of simultaneous quantification of many trace elements even in very small samples and with very low detection limits. This promotes new research in the field of trace elements in biological material. HR-ICP-MS also reduces the time and cost per analysis and broadens the amount of information available from a single specimen.
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Gellein, Kristin; Roos, Per M.; Evje, Lars; Vesterberge, Olof; Flaten, Trond Peder; Nordberg, Monica; Syversen, Tore. Separation of proteins including metallothionein in cerebrospinal fluid by size exclusion HPLC and determination of trace elements by HR-ICP-MS. BRAIN RESEARCH. 1174: 136-142, 2007.
Gellein, Kristin; Lierhagen, Syverin; Brevik, Per Steinar; Teigen, Marte; Kaur, Parvinder; Singh, T.; Flaten, Trond Peder; Syversen, Tore. Trace element profiles in single strands of human hair determined by HR-ICP-MS. BIOLOGICAL TRACE ELEMENT RESEARCH. 123(1-3): 250-260, 2008.
Gellein, Kristin; Skogholt, JH; Aaseth, Jan; Thoresen, GB; Lierhagen, Syverin; Steinnes, E.; Syversen, Tore; Flaten, Trond Peder. Trace elements in cerebrospinal fluid and blood from patients with a rare progressive central and peripheral demyelinating disease. JOURNAL OF THE NEUROLOGICAL SCIENCES. 266(1-2): 70-78, 2008.
Gellein, Kristin; Syversen, Tore; Steinnes, E.; Nilsen, TIL; Dahl, OP; Mitrovic, S; Duraj, D; Flaten, Trond Peder. Trace elements in serum from patients with Parkinson's disease - a prospective case-control study - The Nord-Trondelag Health Study (HUNT). BRAIN RESEARCH. 1219: 111-115, 2008.