Trond Peder Flaten

Geographical associations between aluminium in drinking water and death rates with dementia (including Alzheimer's disease), Parkinson's disease and amyotrophic lateral sclerosis in Norway.

Comparisons of maps and correlation and regression analysis indicate a geographical association between aluminium (Al) in drinking water and registered death rates with dementia (coded from death certificates as the underlying or a contributory cause of death) in Norway. High levels of Al in drinking water are in most cases related to acid precipitation. In general, correlations between aggregate environmental measurements and mortality are a weak source of evidence for risk factors for disease, however, and interpretations regarding cause-and-effect relationships should therefore be made with great care. The major uncertainty probably relates to the use of registered death rates with dementia as a measure of incidence rates of Alzheimers disease. The dementia rates are correlated with population density, and it is possible that the association between AI and dementia might be due to differences in diagnosis and reporting of dementia. Thus, the present study can only be regarded as introductory, and further epidemiological studies are needed to help elucidate the role of AI in Alzheimers disease. The results provide little evidence of an association between AI in drinking water and Parkinsons disease or amyotrophic lateral sclerosis.

The neurotoxicity of iron, copper and manganese in Parkinson's and Wilson's diseases.

Impaired cellular homeostasis of metals, particularly of Cu, Fe and Mn may trigger neurodegeneration through various mechanisms, notably induction of oxidative stress, promotion of α-synuclein aggregation and fibril formation, activation of microglial cells leading to inflammation and impaired production of metalloproteins. In this article we review available studies concerning Fe, Cu and Mn in Parkinsons disease and Wilsons disease. In Parkinsons disease local dysregulation of iron metabolism in the substantia nigra (SN) seems to be related to neurodegeneration with an increase in SN iron concentration, accompanied by decreased SN Cu and ceruloplasmin concentrations and increased free Cu concentrations and decreased ferroxidase activity in the cerebrospinal fluid. Available data in Wilsons disease suggest that substantial increases in CNS Cu concentrations persist for a long time during chelating treatment and that local accumulation of Fe in certain brain nuclei may occur during the course of the disease. Consequences for chelating treatment strategies are discussed.

Aluminium in tea—concentrations, speciation and bioavailability

Abstract Tea ( Camellia sinensis ) is one of a few plants accumulating aluminium (Al), making tea a major source of dietary Al intake. This paper reviews published studies on the concentrations, speciation and bioavailability of Al in tea. With very few exceptions, the total concentration of Al in tea infusions is in the range 1–6 mg l −1 . Probably more than 90% of this Al is bound to organic matter, but the nature of the organic species is unclear. Three studies using size exclusion chromatography provide evidence for Al species in the molecular mass (MM) range 4000–8500 Da, probably polyphenolic complexes. Two ultrafiltration studies indicate the presence of Al species with MMs above 10,000. The relative amount of the different organic Al species in tea infusions is unclear, and even the identity of any of these has not been demonstrated with certainty. A possible exception is Al trioxalate, which may be an important species based on evidence from two 27 Al-NMR studies. It seems fairly well established that drinking tea leads to measurable, but moderate increases in urinary Al excretion. However, the Al present in tea does not seem to be much more bioavailable than that from other dietary sources. Even so, it cannot be dismissed that tea infusions may contain particularly bioavailable and neurotoxic compounds such as Al maltolate, but this is at present speculative.

Metal Concentrations in Cerebrospinal Fluid and Blood Plasma from Patients with Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal degenerative disorder of motor neurons. The cause of this degeneration is unknown, and different causal hypotheses include genetic, viral, traumatic and environmental mechanisms. In this study, we have analyzed metal concentrations in cerebrospinal fluid (CSF) and blood plasma in a well-defined cohort (n = 17) of ALS patients diagnosed with quantitative electromyography. Metal analyses were performed with high-resolution inductively coupled plasma mass spectrometry. Statistically significant higher concentrations of manganese, aluminium, cadmium, cobalt, copper, zinc, lead, vanadium and uranium were found in ALS CSF compared to control CSF. We also report higher concentrations of these metals in ALS CSF than in ALS blood plasma, which indicate mechanisms of accumulation, e.g. inward directed transport. A pattern of multiple toxic metals is seen in ALS CSF. The results support the hypothesis that metals with neurotoxic effects are involved in the pathogenesis of ALS.

Trace Element Profiles in Single Strands of Human Hair Determined by HR-ICP-MS

Trace element analysis of human hair has the potential to reveal retrospective information about an individual’s nutritional status and exposure. As trace elements are incorporated into the hair during the growth process, longitudinal segments of the hair may reflect the body burden during the growth period. We have evaluated the potential of human hair to indicate exposure or nutritional status over time by analysing trace element profiles in single strands of human hair. The hair strands from five healthy and occupationally unexposed subjects were cut into 1-cm long segments starting from the scalp. By using high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS), we achieved profiles of 12 elements in single strands of human hair, namely, Ag, As, Au, Cd, Cu, Hg, Fe, Pb, Se, Sr, U and Zn. We have shown that trace element analysis along single strands of human hair can yield information about essential and toxic elements, and for some elements, can be correlated with seasonal changes in diet and exposure. The information obtained from the trace element profiles of human hair in this study substantiates the potential of hair as a biomarker.

Manganese, Copper, and Zinc in Cerebrospinal Fluid from Patients with Multiple Sclerosis

The concentrations of manganese, copper, and zinc in cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) and patients with no known neurological disease (control group) were measured. Manganese and copper levels were determined by two different analytical methods: atomic absorption spectrometry (AAS) and high-resolution inductively coupled plasma-mass spectrometry (HR-ICP-MS), whereas zinc levels were determined by HR-ICP-MS only. Manganese levels (mean±SEM) were significantly decreased in the CSF of MS patients (1.07±0.13 µg/L, ICP-MS; 1.08±0.11 µg/L, AAS) compared to the levels in the control group (1.78±0.26 µg/L, ICP-MS; 1.51±0.17 µg/L, AAS). Copper levels were significantly elevated in the CSF of MS patients (10.90±1.11 µg/L; ICP-MS, 11.53±0.83 µg/L, AAS) compared to the levels in the control group (8.67±0.49 µg/L, ICP-MS; 9.10±0.62 µg/L, AAS). There were no significant differences between the CSF zinc levels of MS and control patients. The physiological basis for the differences in manganese and copper concentrations between MS patients and controls is unknown, but could be related to alterations in the manganese-containing enzyme glutamine synthetase and the copper-containing enzyme cytochrome oxidase.

Leaching of Trace Elements from Biological Tissue by Formalin Fixation

In studies of trace elements in biological tissue, it is imperative that sample handling does not substantially change element concentrations. In many cases, fresh tissue is not available for study, but formalin-fixed tissue is. Formalin fixation has the potential to leach elements from the tissue, but few studies have been published in this area. The concentrations of 19 elements were determined by high-resolution inductively coupled plasma mass spectrometry in formalin in which human and rat brain samples had been stored for different time durations ranging from weeks up to several years. Additional analysis was carried out in fixed brain samples. There was substantial leaching of elements from the tissue into the formalin, and the leaching varied considerably between different elements. For example, formalin concentrations of As, Cd, Mg, Rb, and Sb increased more than 100-fold upon long-term (years) storage, while for Ni and Cr, the leaching was negligible. The degree of leaching was strongly time-dependent. In conclusion, formalin fixation and storage of biological tissue has the potential to leach substantial fractions of several trace elements from the tissue. The potential of leaching must be critically considered when using formalin-fixed biological tissue in trace metal analysis.

A nation-wide survey of the chemical composition of drinking water in Norway

Water samples were collected from 384 waterworks that supply 70.9% of the Norwegian population. The samples were collected after water treatment and were analysed for 30 constituents. Although most constituents show wide concentration ranges, Norwegian drinking water is generally soft. The median values obtained are: 0.88 mg Si l-1, 0.06 mg Al l-1, 47 micrograms Fe l-1, 0.69 mg Mg l-1, 2.9 mg Ca l-1, 3.8 mg Na l-1, 6 micrograms Mn l-1, 12 micrograms Cu l-1, 14 micrograms Zn l-1, 9 micrograms Ba l-1, 15 micrograms Sr l-1, 0.14 mg K l-1, 58 micrograms F- l-1, 6.4 mg Cl- l-1, 11 micrograms Br- l-1, 0.46 mg NO3- l-1, 5.3 mg SO4(2-) l-1, 2.4 mg TOC l-1, 6.8 (pH), 5) microseconds cm-1 (conductivity) and 11 mg Pt l-1 (colour). Titanium, Pb, Ni, Co, V, Mo, Cd, Be and Li were seldom or never quantified, due to insufficient sensitivity of the ICP (inductively coupled plasma) method. Norwegian quality criteria, which exist for 17 of the constituents examined, are generally fulfilled, indicating that the chemical quality of drinking water, by and large, is good in Norway. For Fe, Ca, Mn, Cu, pH, TOC and colour, however, the norms for good drinking water are exceeded in more than 9% of the samples, reflecting two of the major problems associated with Norwegian drinking water supplies: (i) many water sources contain high concentrations of humic substances; (ii) in large parts of the country, the waters are soft and acidic, and therefore corrosive towards pipes, plumbing and other installations. Most constituents show marked regional distribution patterns, which are discussed in the light of different mechanisms contributing to the chemical composition of drinking water, namely: chemical weathering of mineral matter; atmospheric supply of salt particles from the sea; anthropogenic pollution (including acid precipitation); corrosion of water pipes and plumbing; water treatment; decomposition of organic matter; and hydrological differences.

Separation of proteins including metallothionein in cerebrospinal fluid by size exclusion HPLC and determination of trace elements by HR-ICP-MS.

A method to study the protein binding patterns of trace elements in human cerebrospinal fluid (CSF) is described. Proteins in CSF samples were separated by size exclusion chromatography combined with high performance liquid chromatography (SEC-HPLC). The column was calibrated to separate proteins in the molecular weight range 6-70 kDa. Fractions were then analyzed off-line for trace elements using high resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). We were able to accurately determine more than 10 elements of clinical interest in the CSF fractions. Results are presented for Cd, Mn, Fe, Pb, Cu and Zn. The total concentrations of 16 trace elements in human plasma and CSF are also presented. The method was able to differentiate the relative contribution of metallothionein and other proteins towards metal binding in human CSF.

Concentrations of Cd, Co, Cu, Fe, Mn, Rb, V, and Zn in Formalin-Fixed Brain Tissue in Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex of Guam Determined by High-Resolution ICP-MS

Amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) are neurodegenerative disorders that occurred with extremely high frequency among the native population on Guam, especially in the 1950s and 1960s, but have substantially declined over the last half-century. The etiology of these diseases is unknown, but the most plausible hypothesis centers on imbalances in essential and toxic metals. We have determined the concentrations of Cd, Co, Cu, Fe, Mn, Rb, V, and Zn in formalin-fixed brain tissue collected during the period 1979–1983 from eight Guamanian patients with ALS, four with PDC, and five control subjects using high-resolution inductively coupled plasma-mass spectrometry. The concentrations of Cd are markedly and significantly elevated both in gray and white matter in ALS, but not in PDC patients. The concentrations of Zn are elevated for both patient groups, in both gray and white matter, but only the difference in gray matter for PDC is significant. For the other metals, no significant differences are found.