Biomedical subjects

E Sabbioni

Publications and source records attributed to E Sabbioni.

At least 55 records · Page 3Linked to original sources

PubMed1994

Iron and other metals in neuromelanin, substantia nigra, and putamen of human brain.

Radiochemical neutron activation analysis has been used to determine the concentration of 36 elements in neuromelanin, 22 elements in substantia nigra, and 32 elements in putamen of healthy subjects without signs of neurological disorders. Substantia nigra and putamen tissues were carefully dissected from the brain using special surgical instruments and tools as well as an adequate sampling procedure to avoid the risk of metal contamination during sampling. Neuromelanin was isolated from putamen by a multiple-step procedure (extraction with phosphate buffer, lipid and protein elimination by methanol extraction, and sodium dodecyl sulfate-proteinase). The isolated pigment as well as substantia nigra and putamen underwent neutron activation analysis involving irradiation in a high-neutron-flux reactor, radiochemical separations, and counting of the induced radionuclides by computer-based gamma-ray spectrometry. Iron was the element present in the highest concentration in all analyzed samples. The amount of iron was similar in substantia nigra and putamen (3,000 and 3,830 ng/mg wet weight, respectively) and 10 times higher in neuromelanin (30,800 ng/mg dry weight). Zinc was also present at high levels in three samples, ranging from 16.8 (substantia nigra) to 1,500 ng/mg (neuromelanin). Elements such as Zn, Cr, Se, Sr, Co, Sb, Ni, Hg, Ce, Au, Ag, Ta, and Sc were present in neuromelanin at much higher concentrations than in substantia nigra and putamen. These findings indicate that substantia nigra and putamen contain metals at higher concentrations than observed in blood and that neuromelanin has a particular affinity for metals.

Adult↗

PubMed1993

Effects of trace metals on mouse B16 melanoma cells in culture.

The effects of fourteen metal ions (As3+, As5+, Cd2+, Co2+, Cr3+, Cr6+, Hg2+, Li+, Mg2+, Mn2+, Ni2+, Se4+, V5+, VO2+) on the proliferation and differentiation in mouse B16 melanoma cells cultivated in vitro were analyzed. Cell number assays, melanin, and protein measurements, a 3(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide reduction test (MTT survival test), and a clonal growth assay were performed. At 10(-4)M, metal ions such as As3+, As5+, Cd2+, Cr6+, Se4+, V5+, VO2+, and, to a minor extent, Li+, Hg2+, and Co2+ significantly reduced the number of the B16 melanoma cells. For the same molar concentration, the order of the levels of cell toxicity of the metal compounds to B16 cells as measured by the MTT test was as follows: Hg2+ > Cr6+ = Cd2+ > As3+, As5+, > V5+, VO2+ > Se4+ = Ni2+ = Co2+ = Li+. An increased synthesis of melanin in B16 cells was noted after incubation with Co2+, Ni2+, Cd2+, and Li+, whereas Se4+ had, on the contrary, an inhibiting effect on melanogenesis.

Animals↗

PubMed1993

The intensity of vanadium(V)-induced cytotoxicity and morphological transformation in BALB/3T3 cells is dependent on glutathione-mediated bioreduction to vanadium(IV).

Cytotoxicity and morphological transformation has been studied in BALB/3T3 Cl A31-1-1 mouse embryo cells for ammonium vanadate [vanadium(V)] and vanadyl sulphate [vanadium(IV)] alone or in combination with diethylmaleate (DEM), a cellular glutathione (GSH)-depleting agent. Cells exposed for 24 h to 10(-5) M vanadium(V) alone or in combination with 3 x 10(-6) M DEM showed the characteristic hyperfine EPR signal of vanadium(IV), which was more obvious in the case of exposure to vanadium(V) alone. This suggests that the amount of vanadium(V) reduced to vanadium(IV) decreased in GSH-depleted cells. While vanadium(IV) at concentrations of 3 x 10(-6) M and 10(-5) M was not transforming in the cells, vanadium(V) showed neoplastic transforming activity (P < 0.025 and P < 0.001 for the two doses, respectively) in comparison to controls (vanadium unexposed cells). Cytotoxicity and morphological transformation in cells exposed to vanadium(V) in combination with 3 x 10(-6) M DEM were significantly more intensive (P < 0.005 and P < 0.01 for the two doses of vanadate tested) compared to the corresponding values observed in cells exposed to vanadium(V) alone. This suggests that the final transforming activity response is dependent on the intracellular GSH-mediated mechanism of reduction of vanadium(V) to vanadium(IV): (i) the extent to which vanadium(V) should be bioreduced to less toxic vanadium(IV) via intracellular GSH is a key point in determining the intensity of the observed neoplastic action; (ii) the carcinogenic potential of vanadium(V) should be strictly dependent on its intracellular persistence which could lead to changes in normal metabolic patterns of vanadium(V) in the oxidized form due to lack of GSH-mediated reduction.

3T3 Cells↗

PubMed1993

Use of cell cultures, nuclear and radioanalytical techniques for metallotoxicological studies at the JRC-Ispra.

This paper reviews the JRC-Ispra research activity on toxicological studies related to the environmental and occupational exposure of trace metals, as carried out by a combination of cell culture methodologies with nuclear and radioanalytical techniques. Applications concern the setting of uptake-effect relationships and the study of the mechanisms of toxicity of specific metals (Al, As, Cd, Co, Cr, Mo, Se, V), as well as the establishment of ranking of metal toxicity by carrying out systematic studies (screening tests).

Animals↗

PubMed1993

International project for producing reference values for concentrations of trace elements in human blood and urine--TRACY.

In assessing the concentrations of toxic metals, such as cadmium, chromium, and mercury, in human blood and urine samples to determine whether they are abnormal or not, reliable reference values are needed from populations of nonoccupationally exposed subjects. Numerous publications present concentrations claimed to be typical for the study populations, but they can differ by up to an order of magnitude for a particular element. This is the consequence of general problems that are related to the definition of the reference groups, and the sampling and analytical procedures used, and that make it difficult to define typical and unbiased values. An international group of experts now establishes criteria and procedures to evaluate publications containing information on the concentrations of metals in tissues and body fluids for reference populations. These evaluations have been compiled in a data base (TRACY).

Hazardous Substances↗

PubMed1992

Trace element reference values in tissues from inhabitants of the European Community. II. Examples of strategy adopted and trace element analysis of blood, lymph nodes and cerebrospinal fluid of Italian subjects.

The EURO TERVIHT (Trace Element Reference Values in Human Tissues), recently initiated, aims to establish and compare trace metal reference values in inhabitants from the different EC countries. The project anticipates international cooperation of specialized chemical and toxicological laboratories in Western Europe. In order to overcome the well known and intolerable high fluctuation in published trace metal concentrations in body fluids and tissues, which are mostly due to poor analysis, this paper gives recommendations and strategies for approaching 'background' values measurement practised in the EURO TERVIHT. The focus of the paper is more on quality rather than on quantity of data with particular aspects: (i) well-described protocol for the selection/composition of reference groups (extended epidemiological data plus clinical status); (ii) numerous pre-analytical factors, among which are of paramount importance are ultraclean laboratory air, container material, storage conditions at -20 degrees C; (iii) statistical treatment of the data and the expression of the analytical results (use of refined statistical analysis such as the Lilliefors test to define the type of distribution, normal or log-normal). Results reported here concern the determination of trace elements in whole blood of more than 350 Italian subjects which allowed the proposal of 'reference values' for 12 elements. In lymph nodes and cerebrospinal (CSF) the degree of information acquired is only sufficient to suggest 'indicative' of 'informative' values.

Computers↗

PubMed1992

Trace element reference values in tissues from inhabitants of the European Community. III. The control of preanalytical factors in the biomonitoring of trace elements in biological fluids.

In the context of a programme concerning the determination of trace elements in body fluids and tissues to establish trace element reference values, research has been undertaken on the control of preanalytical factors in order to develop sufficiently accurate and precise guidelines to be applied in routine work by using techniques such as graphite furnace atomic absorption spectroscopy (GFAAS). Aspects investigated are related to the risk of contamination during blood collection and the use of anticoagulants; the risk of losses during storage and freeze-drying as well as the possible risk of contamination arising from trace elements in airborne particulates of the laboratory environment. For the analysis of Al, Ba, Cd, Co, Cr, Mn, Mo, Ni, Sb, W, V and Zn in blood, Teflon cannula is the method of choice. The anticoagulants do not introduce disturbing contaminations of Rb, Se, Zn, while contaminations were observed for Co, Cr, Mn. Radiotracers in 'metabolized form' (radiolabelled rat or rabbit tissues from animals administered with radioisotopes) show that samples stored for 1 month at -20 degrees C have no significant trace metal losses. Strict ambient air quality standard has to be respected (continuous monitoring) due to the possibility of element contaminations inside the laboratory. The use of matrix modifiers could represent a toxicological risk to the operators. Critical factors should be considered ('metal sheets') for each element in each matrix. For instance 27 factors for Cr in serum have been suggested.

Air Pollutants, Occupational↗

PubMed1992

Vanadium effect on the activity of horseradish peroxidase, catalase, glutathione peroxidase, and superoxide dismutase in vitro.

The effect of vanadium (V) on the activity of horseradish peroxidase, catalase, glutathione peroxidase, and superoxide dismutase has been studied. A competitive inhibition pattern was evident for vanadate ions on the activity of horseradish peroxidase (Ki = 41.2 microM). No significant inhibitory effects were found when V(V) was tested with catalase and when either V(IV) or V(V) were assayed with glutathione peroxidase. For the latter, the effect of V on the different components of the reaction system was investigated. V(V) did not significantly affect SOD activity when assayed with the sulfite method, which is devoid of interferences with V(V); however, there was an apparent inhibitory dose-response pattern for either V(IV) or V(V) using the pyrogallol assay, owing to an interference of pyrogallol with the metal. Besides, no significant binding of V(IV) or V(V) to the enzyme could be demonstrated. The lack of a direct inhibitory effect of V on the activity of the main antioxidant enzymes suggests that many biological and toxicological effects of V may be mediated more by oxidative reactions of the metal or of its complexes with physiologically relevant biomolecules than by a direct modulation of enzymatic activities.

Catalase↗

PubMed1992

Metabolic studies as a basis for the interpretation of metal toxicity.

The toxicity of metal compounds has traditionally been regarded as a function of dose and potency of the metal itself. In recent years, however, it has become clear that several metals and metalloids undergo transformations in mammalian tissues and that metabolism may have important implications in clinical pharmacology, toxicology, and environmental health. In this paper, data obtained from recent metabolic studies are reviewed as a basis for the interpretation of biological effects and kinetic patterns of metals of major importance as environmental pollutants.

Animals↗

PubMed1992

Trace elements in dialysis fluids and assessment of the exposure of patients on regular hemodialysis, hemofiltration and continuous ambulatory peritoneal dialysis.

Forty-four elements (Al, Sb, As, Ba, Be, B, Br, Cd, Ce, Co, Cr, Cs, Cu, Eu, Ga, Au, Hf, In, Ir, Fe, La, Lu, Mn, Hg, Mo, Nd, Ni, Pb, Rb, Sm, Sc, Se, Ag, Sr, Ta, Tb, Tl, Th, Sn, W, U, V, Zn, Zr) have been determined in the dialysate for hemodialysis (HD) and fluids for hemofiltration (HF) and continuous ambulatory peritoneal dialysis (CAPD). Multiple determinations have been performed for each dialysis fluid. Several trace elements (TE) showed remarkably elevated average levels; moreover, different bathes of the same commercial product may present a wide variability in TE concentration. The data point out the pivotal role of dialysis fluids in contributing to TE imbalance in dialysis patients and allow the assessment of the potential element exposure of patients on regular dialytic treatment. Patients on HD treatment would be exposed on a weekly basis to milligrams of Al, B, Ba, Br, Cu, Fe, Ni, Pb, Rb, Sr and Zn; on HF, the highest exposures are due to Al, B, Br, Fe, Pb and Zn; on CAPD to B, Br, Fe and Zn. The weekly exposure for several TE appears to be 50- to 12,000-fold higher than the corresponding values on the amount absorbed via the diet (HD: Au, Ba, Be, Ce, Ga, La, Sc, Ta, Th, V, Zr; HF: Be, Ce, Ta, Th, V, Zr; CAPD: Au, Be, Ce, Ga, V, Zr).(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodialysis Solutions↗

PubMed1992

Multi-element follow up in biological specimens of hard metal pneumoconiosis.

The movement of Co and the other components of the hard metal in the body fluids, their solubility, their links to the cells and proteins of the body, and their clearance are largely unknown. The first aim of this work is to evaluate whether Neutron Activation Analysis (NAA), a new analytical technique based on the radiochemical separation of samples irradiated in a Nuclear Reactor, may be suitable for studying the movement of elements in tissues or body fluids of workers over time. We have investigated seven hard metal workers, all employed in the grinding process, with NAA studies (single study in two, follow-up in five) of 29 elements on lung tissue, BAL fluid, blood, urine, pubic hair, toenails and sperm. In three, the diagnosis of hard metal pneumoconiosis was easy; in the other four, due to evident bilateral hilar lymphadenopathy, it was difficult to distinguish between pneumoconiosis and sarcoidosis stage II, and the final diagnosis, after pulmonary biopsy, was hard metal pneumoconiosis in three, and sarcoidosis in one. In spite of high potential, NAA gives a number of unexpected results, with apparent controversies and no clear relationship in the evolution of levels of Co, W and Ta: there is no simple explanation for such apparent inconsistencies at present, so that the study of the movement of elements in body fluid sometimes appears disappointing with this technique. Other observations were noted from the data available: 1) the concentration of elements (Co, Ta, W) in lung tissue is far higher than in BAL fluid, but the factor is so variable that BAL fluid cannot be taken as representative of the concentration of elements in lung tissue. 2) High concentrations in tissues or body fluids are indicative for exposure, but not for disease. In the light of available data, there are no levels above which development of disease is inevitable. 3) When the problem is to distinguish between sarcoidosis and pneumoconiosis in exposed subjects, the concentration of elements is of no value, and the pulmonary biopsy is still necessary. However a NAA study may be helpful to confirm the presence of the offending agent, and to avoid pulmonary biopsy in cases where the occupational history is unclear.

Adult↗

PubMed1991

Aluminum effect on the activity of superoxide dismutase and of other antioxygenic enzymes in vitro.

The effect of Al on superoxide dismutase (SOD) and on other antioxygenic enzymes: horseradish peroxidase, catalase, and glutathione peroxidase, has been investigated in vitro. In the case of SOD, the effect of metal chelators (EDTA and deferoxamine) and a possible synergistic effect with iron salts have also been tested using the pyrogallol assay. There is no significant inhibitory effect of Al on the activity of any of the above-mentioned enzymes. Noticeable increases in SOD activity were observed when metal chelators were added to the medium, but not when high concentrations of Al were present too, in the case of deferoxamine (DFO). The former fact seems to be a consequence of the chelation of transition metal ions that catalyze pyrogallol autoxidation by a mechanism not inhibitable by SOD, interfering in its action, which may account for part of the DFO antioxidant effect observed in vivo. The latter phenomenon could be owing to a saturation of the chelating capacity of DFO by an excess of Al present in the medium, which should bring the system back to the interfering conditions explained above. It can be concluded that Al, either in the presence or in the absence of iron salts, does not inhibit SOD activity in vitro. Moreover, no significant binding of Al to SOD was demonstrated, and the amounts of its metal constituents, Cu and Zn, were not affected by preincubation of the enzyme with Al. The effect of the different compounds tested on the rate of autoxidation of the indicating scavenger, pyrogallol, and a suitable hypothesis on their role in the oxidation process are also discussed.

Aluminum↗

PubMed1991

Biliary excretion of barium in the rat.

Biliary excretion of barium was studied in Sprague-Dawley bile-duct-cannulated rats injected intravenously with 1.8 micrograms Ba/rat as 133Ba-labeled barium chloride. Approximately 0.5% of the barium dose was excreted into bile within 2 h. The time-course profile of biliary excretion of the radiotracer closely reflected that of plasma concentrations. Biliary barium levels reached their peak in the first 15-min period after administration and rapidly declined thereafter. The plasma-to-bile barium-concentration ratio was approx 1 at 2 h after injection. There was no tendency of barium to concentrate in liver, and the 133Ba levels in stomach and small intestine largely exceeded hepatic levels. There is evidence indicating that barium is predominantly excreted with feces following parenteral administration in rats and humans. The results of this study suggest that biliary excretion is of little quantitative importance and that physiological routes other than bile contribute to elimination of barium by the digestive tract.

Animals↗

PubMed1991

Cellular retention, cytotoxicity and morphological transformation by vanadium(IV) and vanadium(V) in BALB/3T3 cell lines.

Cytotoxicity, morphological transformation and cellular retention have been studied in BALB/3T3 Cl A 31-1-1 cells for ammonium or sodium vanadate [vanadium(V)] and for vanadyl sulphate [vanadium(IV)]. A morphological transformation focus assay showed transforming activity for vanadium(V) (P less than 0.005 at concentrations of 3 x 10(-6) or higher) while vanadium(IV) was not transforming in the cells. Cytotoxicity was higher for vanadium(V) than for vanadium(IV); this was particularly clear at doses from 5 x 10(-6) to 5 x 10(-5) M. The cellular retention of both vanadate and vanadyl compounds at 24, 48 and 72 h incubation was similar. At concentrations lower than 10(-6) M vanadate, the retention was linear with the dose, while at higher exposures the vanadium taken up by the cells levelled off or slightly decreased. Exposure to 10(-6) M and 10(-5) M vanadium(V) for 3 and 24 h as well as to 10(-6) M for 48 and 72 h yielded greater than 94% vanadium in the cytosol, but exposure to a toxic dose (10(-5) M) for 48 and 72 h yielded 20% vanadium associated with cellular organelles, which suggests that some sites in the cytosol become saturated with vanadium. The corresponding gel-filtration experiments indicate that a redistribution of the element among the cytosol components occurs with time.

Animals↗

PubMed1991

Cellular retention, toxicity and carcinogenic potential of seafood arsenic. I. Lack of cytotoxicity and transforming activity of arsenobetaine in the BALB/3T3 cell line.

Cytotoxicity, morphological neoplastic transformation, intracellular retention and metabolic behaviour have been investigated in BALB/3T3 Cl A 31-1-1 cells for arsenobetaine, the main form of arsenic in certain seafoods, in comparison to inorganic sodium arsenite. In order to avoid false results, particular attention was paid to the purity, checking for the presence of any trace amounts of inorganic arsenic as well as methylated contaminants in the chemically synthesized arsenobetaine. Cytotoxicity and morphological transformation assays gave obvious positive results for sodium arsenite at a dose exposure of 10 microM. On the other hand, concentrations of arsenobetaine as high as 500 microM failed to induce either cytotoxic effects or neoplastic transformations. The absence of cytotoxicity and transforming potential of arsenobetaine in comparison to inorganic arsenite can be explained by the different degree of retention and the intracellular behaviour of the two arsenic species. Cellular retention of arsenobetaine was dose dependent for exposure concentrations ranging from 1 to 500 microM with a mechanism resembling a simple diffusion (1.4 and 760 pmol of As/10(6) cells were cell associated for the two concentrations at 24 h respectively). About 95% of the intracellular arsenobetaine was present in the cytosol fraction and the attempt to detect any intracellular degradation of the organoarsenic compound failed. Thus, the low retention efficiency of arsenobetaine, its inability to interact with intracellular components and the absence of biotransformation in the cell could explain the lack of cytotoxicity and transforming potential observed in the BALB/3T3 cells. These findings reinforce the view that in humans exposed to different chemical species of arsenic the contribution to the total health risk, including the carcinogenic potential, of arsenobetaine ingested with marine foodstuffs would be negligible.

Animals↗

PubMed1990

Trace element reference values in tissues from inhabitants of the European community. I. A study of 46 elements in urine, blood and serum of Italian subjects.

Neutron activation analysis-electrothermal atomic absorption spectroscopy (ETA-AAS) and inductively coupled plasma atomic emission spectrometry (ICP-AES) have been used for the determination of 46 elements in urine, 35 in blood and 26 in serum of unexposed Italian subjects living in the same region (Lombardy). The results allowed the proposal of reference values for various elements determined in more than 350 healthy subjects, these being Ag, Al, As, Be, Bi, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Sb, Se, Tl, V, Zn, in urine; Ag, As, Bi, Cd, Cr, Co, Cu, Hg, Pb, Se, Tl, Zn in blood; and Ag, Al, Be, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Se, Tl, V, Zn in serum (or plasma). For all other elements indicative values are suggested. In addition to the mean value and the "reference range", a "range of uncertainty" and an upper limit above which metabolic abnormalities could be expected have also been defined on the basis of simple statistical considerations.

Humans↗

PubMed1990

Trace metal lung disease: in vitro interaction of hard metals with human lung and plasma components.

Hard metal pneumoconiosis is an occupational pulmonary disease caused by long-term exposure to dust produced in the hard metal industry. In vitro experiments have been carried out to study the solubility and metabolic behaviour in human lung tissue and plasma of hard metal alloy constituents such as cobalt, tungsten, tantalum, titanium and niobium. The experiments were carried out using 60Co, 187W, 182Ta, 44Ti and 95Nb radiotracers in combination with neutron activation, radio-release tests and gel filtration techniques. Leaching experiments from neutron-irradiated hard metal dust showed that cobalt was highly soluble, especially in the lung cytosol and plasma, in comparison with tantalum and tungsten. The gel filtration experiments showed three biochemical pools of cobalt in both lung and plasma components, in accordance with the hypothesis that cobalt represents the allergic factor in the development of hard metal disease. High affinity for proteins was observed for Nb, Ta and Ti, but not for W, in agreement with the dissimilar biological half-lives of these elements in the body. The different ability of the metals to interact with biochemical components and to be solubilized in biological media may explain the various degrees of retention in the lung, which would influence the metabolic pathways. This would explain the presence of Co, Ta and W in body fluids, as well as in the public hair and toenails of hard metal workers.

Dust↗

PubMed1990

Titanium nitride as a coating for surgical instruments used to collect human tissue for trace metal analysis.

When metallic surgical instruments are used to collect human tissue, metal contamination may occur, making accurate ultra-trace metal determinations very difficult. In order to reduce this risk as much as possible, surgical instruments made from a stainless-steel core covered by a film of titanium nitride, a very hard compound with high chemical stability and very good wear resistance, were prepared. The degree of risk from trace metal contamination during sample collection was investigated by neutron activation analysis and a radio-release in vitro serum test. As examples of their application, the titanium nitride coated instruments were used to determine Co, Cr and W in the skin of unexposed subjects and of uraemic patients under regular dialysis treatment.

Humans↗