Ulf Lindh

Levels of antimony, arsenic, cadmium, copper, lead, mercury, selenium, silver, tin and zinc in bone tissue of industrially exposed workers

The contents of the elements antimony, arsenic, cadmium, copper, lead, mercury, selenium, silver, tin and zinc in bone tissue from autopsy specimens of the femur of workers who had been exposed to a large number of metals in a smeltery and refinery in Northern Sweden as well as of a control group have been quantitatively assayed. The analytical techniques used were atomic absorption spectrophotometry, neutron activation analysis and particle induced X-ray emission analysis (PIXE) in a proton microprobe. Increased levels of lead in the bone tissue of exposed workers compared to a non-exposed control group were observed. The median level of lead in the group of exposed workers exceeded the corresponding value of the control group about 5 times. Using the proton microprobe in the PIXE-mode, concentration profiles of copper, lead and zinc were examined within the Haversian system of the bone samples.

Reduced zinc in peripheral blood cells from patients with inflammatory connective tissue diseases

By the use of the nuclear microprobe technique, the concentrations of zinc in isolated erythrocytes, platelets, and granulocytes were measured in patients with rheumatoid arthritis, other inflammatory arthritides, and scleroderma. Markedly reduced cellular zinc values were found compared to those measured in healthy subjects. No relation was found to inflammatory activity or disease duration. Plasma zinc was reduced in the majority of the patients and was negatively correlated to the inflammatory activity estimated by ESR and serum orosomucoid. No relation was found between total zinc values in plasma or cells or disease duration. Corticosteroid therapy was instituted in a number of the patients with inflammatory arthritides and induced a significant elevation of total zinc in all cell types, although normalization was not acheived. Plasma zinc values remained unchanged during the treatment.

Biological Functions of the Elements

Much discussion has taken place with regard to how to define the essentiality of elements, particularly trace elements. The earliest definition was actually borrowed from protein chemistry. In this definition, an element is essential if:

Microprobe analysis of lead in human femur by proton induced X-ray emission (PIXE)

A method is described for the measurement of the distribution of lead in bone tissue. Two cases of human femur have been analyzed; one worker was exposed to lead in heavy metal industry, the other case presents a reference worker from the same environment not excessively exposed to lead. Lead was determined through proton induced X-ray emission using microprobe technique. The mean lead concentration in the poisoned and the reference case was 70 and 30 ppm, respectively. The reference case showed an even lead distribution in the femur, while the poisoned case exhibited peaks in the distribution indicating that exposure to lead was not evenly distributed. The described technique has potential for microanalysis within the Haversian system for recording the history of exposure.

Sequential changes in Fe, Cu, and Zn in target organs during early Coxsackievirus B3 infection in mice.

In Coxsackievirus B3 (CB3) infection, the heart and pancreas are major target organs and, as a general host response, an associated immune activation and acute phase reaction develops. Although iron (Fe), copper (Cu), and zinc (Zn) are involved in these responses, sequential trace element changes in different target organs of infection have not been studied to date. In the present study, Fe, Cu, and Zn were measured through inductively coupled plasma mass spectrometry (ICP-MS) in the plasma, liver, spleen, heart, and pancreas during the early phase (d 1 and 3) of CB3 infection in female Balb / c mice. The severity of the infection was assessed through clinical signs of disease and histopathology of the heart and pancreas, including staining of CD4 and CD8 cells in the pancreas. During infection, the concentrations of Fe, Cu, and Zn changed in the plasma, liver, and pancreas, but not in the spleen and heart. The changes in plasma Cu, Zn, and Fe seemed to be biphasic with a decrease at d 1 that turned into increased levels by d 3. Cu showed similar biphasic changes in the liver, spleen, and pancreas, whereas, for Zn and Fe, this pattern was only evident in the liver. In the pancreas, the reverse response occurred with pronounced decreases in Fe (23%, p<0.05) and Zn (64%, p<0.01) at d 3. Although the pathophysiological interpretation of these findings requires further research, the sequential determination of these elements may be of clinical value in enterovirus infections in deciding the stage of disease development.

Protective effects of selenium against mercury toxicity as studied in the rat liver and kidney by nuclear analytical techniques

Mercuric chloride and sodium selenite were separately administered to male rats in the drinking water or in a combination (2.5 mmol Hg/L and 0.1 mmol Se/L). The mercuric chloride group showed histopathological lesions, as evidenced by cell necrosis in the liver and tubular necrosis in the kidney. The sodium selenite group showed some depression in growth, but pathological changes were found neither in the liver nor in the kidney. Simultaneous administration of both compounds produced a protective effect on weight loss and histopathology. These effects were associated with some small structures in the kidney proximal tubules and to some structure in the extracellular space in the liver. Thin, unstained cryosections were freeze-dried and examined in the Studsvik Nuclear Microprobe. The structures observed in the liver and the kidney were shown to contain both selenium and mercury.

Trace element changes in the pancreas during viral infection in mice.

Introduction The trigger for some cases of juvenile diabetes has been suggested to be an interaction between a virus and various trace elements. Infection with human coxsackievirus B3 (CB3) in the murine model results in viral replication and inflammation in the pancreas. Aim To determine how infection affects the trace element balance in the pancreas. Methodology Concentrations of the following trace elements were measured in the serum and pancreas during the early phase (days 1 and 3) of CB3 infection in female Balb/c mice: aluminium, arsenic, cadmium (Cd), calcium (Ca), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), magnesium (Mg), manganese (Mn), mercury (Hg), selenium, silver, vanadium (V), and zinc (Zn). The trace element concentrations were measured through inductively coupled plasma mass spectrometry. The histopathology was established by hematoxylin–eosin techniques and immunohistochemical staining of both CD4 and CD8 cells of the pancreas. Results Infected mice developed expected clinical signs of disease. The only changes at day 1 occurred in the serum, with a pronounced decrease in the Zn concentration and a small increase in the V concentration. At day 3, concentrations of several trace elements, including Cu, Zn, Fe, Ca, V, and Mn, showed pronounced changes in both the serum and the pancreas. Ca, Cu, Mg, Mn, and V, but none of the potentially toxic elements, accumulated in the pancreas. Cu and V concentrations increased in the serum as well. Conclusion Several trace element changes, preceding the development of pancreatitis, occurred in the pancreas in this viral infection, the exact pathogenic interpretation of which warrants further studies.

Trace element distribution in heart tissue sections studied by nuclear microscopy is changed in Coxsackie virus B3 myocarditis in methyl mercury-exposed mice.

Methyl mercury (MeHg) has been shown to change Coxsackie virus type B3 (CB3) myocarditis in a direction compatible with the development of chronic disease. Murine models of CB3 myocarditis closely mimic the pathogenesis in humans. There are also indications that metals, such as mercury, and trace elements may interact and adversely affect viral replication and development of inflammatory lesions. The effects of low-dose MeHg exposure on myocardial trace element distribution, as determined by means of nuclear microscopy, was studied in CB3 myocarditis. Balb/c mice were fed a MeHg-containing diet (3.9 mg/kg diet) for 12 wk prior to infection. Areas of inflammatory lesions in the myocardium were identified by traditional histologic examination, and serial tissue sections in these selected areas were used for immune histology (macrophages), in situ hybridization of virus genomes, and nuclear microscopy of tissue trace element distribution. Areas with no inflammation or virus were compared with areas of ongoing inflammation and viral replication. In the inflammatory lesions of MeHg-exposed mice as compared to nonexposed mice, the myocardial contents of calcium (Ca), manganese (Mn), and iron (Fe) were significantly increased, whereas the zinc (Zn) content was decreased. The increased Ca and decreased Zn contents in the inflamed heart may partly explain a more severe disease in MeHg-exposed individuals. Although not significant in the present study, with a limited number of mice, the inflammatory and necrotic lesions in the ventricular myocardium on d 7 of the infection was increased by 50% (from 2.2% to 3.3% of the tissue section area) in MeHg-exposed mice and, also, there was a tendency of increased persistence of virus with MeHg exposure. No increased MeHg uptake, either in the inflammatory lesions or in the areas of noninflamed heart tissue in infected mice, could be detected. The present results indicate that a “competition” exists between potentially toxic heavy metals from the environment/diet and important trace elements in the body and that a disturbed trace element balance adversely influences the development of pathophysiologic changes in inflammatory heart disease.

Elemental mapping of tissue sections by means of micro particle-induced x-ray emission spectroscopy and computer graphics

Abstract The elemental distribution within microregions of tissue sections can be revealed by using the nuclear microprobe. The freeze-dried tissue sections are scanned under a 5-μm proton beam and induced x-rays from inner electron shells are continuously recorded along with the actual plane coordinates. The contents of elements heavier than sodium in tissues can be traced in relative amounts as low as 0.5 μg g−1. When energy-dispersive detection of induced x-rays is used, multi-element capacity is achieved. The recorded spectra are stored on tape and processed off-line to produce elemental maps of the tissue section at better than cellular resolution. Although qualitative mapping is economic, quantitative maps can be produced by grey scales or colour graphics.

Relation between trace element levels in plasma and myocardium during coxsackievirus B3 myocarditis in the mouse

During most infections the plasma levels of trace elements change, but it is not clear if this reflects changes in the infected tissues. Coxsackievirus B3 (CB3) infection may result in viral replication, subsequent inflammation and changed trace element levels in the myocardium. In the present study, the trace element levels in the plasma and heart of adult male A/J mice were determined during the pre-inflammatory stage (day 4) of CB3 myocarditis for the following trace elements: aluminium (Al), arsenic (As), calcium (Ca), cobalt (Co), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), selenium (Se), silver (Ag), vanadium (V) and zinc (Zn). The severity of the infection was assessed through clinical signs of disease and trace element levels were measured through inductively-coupled plasma mass-spectrometry (ICP-MS). In the heart, the levels decreased for V (59%; p < 0.01), Co (38%; p < 0.01), Al (81%; p <  0.01), As (66%; p < 0.01) and Se (16%; p < 0.01). Increased levels were detected for Mn (13%; p < 0.05), Fe (48%; p < 0.01), Cu (34%; p < 0.01) and Ag (46%; p <  0.01). In the plasma, decreases were detected in the level of Zn (32%; p < 0.05), whereas increases were seen in Mn (362%; p < 0.05), Fe (272%; p < 0.01), Co (71%; p < 0.05), Cu (25%; n.s.) and Mg (43%; p < 0.01) levels. A correlation was found between the levels in plasma and myocardium for Co (rs=−0.636; p < 0.05), Fe (rs=0.764; p < 0.05), Mn (rs=0.682; p < 0.05) and Mg (rs=−0.791; p < 0.05). Thus, determination of some of these trace elements in the plasma may be useful to indicate target tissue involvement in the early pre- inflammatory stage of an infectious disease. Some of these elements are important nutrients for the immune system, while others may be associated with the development of disease complications, such as cardiac arrhythmias.