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Biomedical subjects

E Sabbioni

Publications and source records attributed to E Sabbioni.

At least 73 records · Page 4Linked to original sources

Trace metal lung diseases: a new fatal case of hard metal pneumoconiosis.

Four subjects working in sharpening and grinding operations of hard metal tools were examined. Only 1 worker, a 37-year-old female exposed for 7 years to hard metal dusts, developed hard metal pneumoconiosis, which rapidly progressed to death. Cytology of the bronchoalveolar lavage (BAL) showed a high number of eosinophils, more than 30% of the cell population. Biopsy of the lung revealed interstitial fibrosis with hyperplasia of the pneumocytes of the second type and inflammatory cellular infiltration of the interstitium. High tungsten (W) and tantalum concentrations were determined in the admission BAL and in the biopsy 4 months later by neutron activation analysis while cobalt (Co) levels were near to normal values. The content of Co and W in blood and urine and particularly in pubic hair and toe nails of the patients was significantly higher than the normal values. This suggests that these biological specimens could be used as indicators of chronic exposure to hard metal dusts.

Adult↗

Trace element analysis in environmental and occupational health: box plot representation of elemental composition results.

Box plots are used in the visual representation of large data sets and in exploratory data analysis. They display batches of data with five values being used to describe the data set. These are the median, the upper and lower extremes of the range of values and the 75 and 25 percentiles. A notch about the median, e.g. at the 95 percent level of significance, can be incorporated in the display allowing the difference between the medians of different sets to be established. The method, although not recently established, has so far found little application in the analytical field. Hence, in an effort to strengthen its applicability, the features and capabilities of box plots, in terms of data reporting and insight into the data set, are here described through elemental composition studies in relation to environmental and occupational health.

Cobalt↗

Vanadium transport across placenta and milk of rats to the fetus and newborn.

The transport of vanadium across placenta and milk rats was studied by iv injection of low doses of 48V-labeled pentavanadate (0.1 micrograms V/rat) to pregnant and nursing rats. Significant concentrations of vanadium were found in the liver, intestine, and kidneys of the fetuses, showing that vanadium is capable to pass the placental barrier and, thus, being metabolized in the fetuses. Two days after injection of 0.1 micrograms V/rat as 48V-labeled vanadate to nursing rats, 34 ng V/g milk were found, decreasing to 4 ng V/g at the d 12 after dosing. The corresponding suckling rats showed a significant absorption of vanadium taken up by the milk, as suggested by the presence in their intestine, where 48V is easily absorbed in form of low molecular weight components. Vanadium in milk may be transported in the form of a biocomplex with lactoferrin, since at 12 d after injection, the 48V in the rat milk was mainly found in fractions corresponding to proteins. In weanling rats, 7 d postlactation and 18 d after administration of vanadium to the mother, only very small amounts of 48V were still present in the organs. Excretion studies on weanling rats for 7 d showed that vanadium is rapidly released mainly via feces when earlier taken up by the milk of iv injected mothers and having the same elimination pattern as the milk, which lost about 80% of its vanadium concentration after 12 d.

Animals↗

Salts as a source of metals in dialysis fluids: an assessment study by means of neutron activation analysis.

Thirty-nine trace metals were determined by neutron activation analysis (NAA) in nine salts (glucose, NaCl, KCl, CaCl2, MgCl2, Na-lactate, Na-acetate, NaHCO3 and NaOH), from different European producers, used in the preparation of dialysis fluids. Metal concentrations vary widely from less than 1 ng g-1 to several micrograms per gram. The data are used to assess the potential metal contribution of the salts to a hypothetical dialysis fluid. A comparison of these calculations with NAA of commercial haemodialysis solutions, and water used for their preparation, suggests that salts are the main source of metal contamination of the dialysate. Despite this, the chemical purity of the salts analyzed is considered to be good and it would be unrealistic to expect a clearly better chemical quality on a commercial scale. In order to protect the health of dialysis patients against abnormal metal exposure, toxicological research directed towards the estimation of the effective daily metal exposure and the determination of possible metal overloads in dialysis patients is necessary. A standardization of the dialysis systems actually used is also an important aspect if uncontrolled metal contamination of the dialysis fluid is to be avoided.

Humans↗

Clinical and histological results of long-term management of aluminium overloading in uraemic patients with desferrioxamine.

Aluminium introxication in uraemic patients has been reported both in epidemic and sporadic forms. Desferrioxamine (DFO) results in strong Al mobilisation, but definitive treatment schedules, times of stop, and actual long-term Al removal her not been established. This study was carried out on three sporadic cases of Al intoxication treated with DFO for 3 1/2, 4 1/2 and 1 years. Clinical and laboratory parameters were employed to check the brain, bone and red cell status. Direct evaluation of Al kinetics showed that actual Al removal may be overestimated. In our experience it did not exceed 100 mg/year, and the ratio (DFO used/Al removed) decreased to 150 g/25 mg after two years of DFO, though considerable tissue deposits persisted in the patient who died after 3 1/2 years of treatment. Despite unexplained EEG worsening, neurological symptoms improved. Relapses, however, occurred after many years of DFO. Bone status improvement, at least in parathyroidectomised patients, proved to be only partial and time-related. The therapeutic effectiveness of DFO in these patients seemed to be exhausted after two years even if Al deposits had not vanished.

Adult↗

Criteria for reference value assessment of elements in human tissues.

The availability of updated and reliable reference values for elements in biological tissues and fluids plays a key role in the correct planning and performance of clinical, toxicological and environmental studies. The basic principles for a proper analytical approach in order to obtain such data are outlined. This in turn should significantly reduce the wide range of figures reported for most elements as "normal" intervals in the scientific literature. Some applications of these guidelines are illustrated in detail in the case of human lungs, liver and kidneys for which tentative reference values are assessed for a number of minor and trace elements, namely, Al, Ba, Cd, Cr, Cu, Li, Mg, Mn, Pb, Sr, V and Zn.

Humans↗

Kinetics of chromium during peritoneal dialysis.

This study describes investigations on the possible mechanisms involved in the transfer of Cr from the dialysate to the blood during peritoneal dialysis. The ability of Cr(III) compounds to penetrate across a membrane at physiological pH seems rather questionable, as it is well known that Cr(III) tends to form polymeric chains. Therefore, a systematic study was undertaken to describe the pathways involved in this transport. The characteristics during 'in vitro' dialysis were compared to the behaviour of Cr during acute 'in vivo' experiments on anesthetized rabbits. It appeared that lactate, a common substance of the dialysate, plays an extremely important role in the mobility and subsequent transfer of Cr(III) across the peritoneum.

Carbon Radioisotopes↗

Retention of intratracheally instilled and ingested tetravalent and pentavalent vanadium in the rat.

The retention, subcellular distribution in the liver, kidneys and lungs and binding of vanadium in the rat were investigated at 3 h, 1 d and 12 d after intratracheal instillation of 200 ng/kg body weight of 48V-labelled pentavalent and tetravalent vanadium. The metabolic patterns of both chemical forms of vanadium were similar. The lungs, liver, kidneys, bone, testes and spleen are the target tissues at risk, vanadium being removed from them with time at different rates. Pulmonary vanadium clearance was initially rapid - 80-85% of the 48V was removed within 3 h. At 12 d about 2% of the element was still present in the lung. Intracellularly, the major part of liver, kidney and lung vanadium was present in the nuclear fraction (30-40% of the homogenate), followed by cytosol and mitochondrial fractions. Gel filtration chromatography of the lung cytosol showed two biochemical pools of vanadium: the first corresponding to protein bound vanadium, which may be involved in the long-term accumulation of the element in the lung, the second pool representing a diffusible vanadium form. The retention of the tetravalent and pentavalent vanadium forms was also investigated 1 d after oral administration. No obvious differences were observed in the distribution pattern of 48V in the tissues, the retention factor being higher by two orders of magnitude in comparison with the intratracheally instilled animals. These findings suggest that the metabolic pathways of tetravalent and pentavalent vanadium are independent of the route of vanadium exposure.

Administration, Oral↗

Cellular uptake and metabolic reduction of pentavalent to trivalent arsenic as determinants of cytotoxicity and morphological transformation.

Cytotoxicity, morphological neoplastic transformation, cellular uptake and metabolic reduction were determined in BALB/3T3 Cl A31-1-1 cells for trivalent arsenic (sodium arsenite, As3+) and for pentavalent arsenic (sodium arsenate, As5+). The levels of cellular uptake of 73As-labelled sodium arsenite and arsenate were dose-dependent and highest in the first hour. At equimolar concentration (3 X 10(-6) M), cellular uptake was 4-fold higher for As3+ than for As5+. Cytotoxicity was higher for As3+ than for As5+, but when correlated to total As cell burden it showed no significant difference for the two forms. Morphological transformation focus assays showed transforming activity for both As3+ and As5+, with relative transformation frequencies also of approximately 4:1. Recovery from the cytosol after exposure for 1-24 h was greater than 90% for either form of absorbed As. Exposure to As3+ yielded 100% as As3+ in cytosol, but exposure to As5+ yielded greater than 70% as As3+, showing a high rate of intracellular metabolic reduction. No methylated metabolites were detected by ion-exchange chromatography. After 24-h incubation in cell-free medium, oxidation of As3+ to As5+ occurred up to 30% of the dose, but incubation in the presence of cells lowered the oxidation level to 4%. As5+ was recovered unchanged from cell-free medium (24-h incubation), but in the presence of the cells it yielded up to 5% as As3+ within 24 h and the cumulative release of As3+ by cells exposed to As5+ was dose-dependent. Glutathione depletion by diethylmaleate inhibited reduction of As5+ to As3+ by these cells up to 25% of controls, showing that As5+ reduction is partly dependent on glutathione. These results suggest that As3+ is the form responsible for the cytotoxic and transforming effects, independently of the valence state of the inorganic arsenic in the culture medium.

Animals↗

Multielement determination of metals in biological specimens of hard metal workers: a study carried out by neutron activation analysis.

Multielemental analysis, using neutron activation, was carried out on the urine, whole blood, pubic hair and toenails of thirty subjects occupationally exposed to hard metal dusts. A high concentration of Co, W and Cr was observed in all samples analysed. The concentrations determined, when subjected to statistical analysis using pattern recognition techniques (e.g. cluster analysis), indicated a positive correlation, at p = 0.001, for the pair (Co, W) in urine and blood, as well as a possible influence of Cr on this pair.

Adolescent↗

Rare-earth pneumoconiosis: a new case.

A new case of rare-earth (RE) pneumoconiosis is described. The subject had worked as a photoengraver for 13 years and had not been exposed for 17 years. Chest X-ray showed a diffuse nodular pattern (q 2/3-ILO/1980). The patient was asymptomatic despite a restrictive spirometric impairment. The diagnosis derived from the finding, in the bronchoalveolar lavage fluid, of abnormal levels of La, Ce, Nd, Sm, Tb, Yb, and Lu. The presence of these elements was demonstrated by two methods: the neutron activation analysis and (as regards Ce alone) the X-ray energy spectrometry of mineral particles observed with electron microscope. Abnormal levels of rare earths were demonstrated also in the nails, suggesting an absorption of the RE from the lung.

Cerium↗

Thallium-induced testicular toxicity in the rat.

Reproductive tract functions were studied in adult male Wistar rats given 10 ppm thallium as thallium sulfate in the drinking water. After 60 days of treatment, spermatozoa isolated from the cauda epididymides and vas deferens showed reduced motility and immature germ cells were found in the tubular lumen. Histological examination of testes in thallium-treated animals revealed disarrangement of the tubular epithelium and ultrastructural changes in the Sertoli cells with cytoplasmic vacuolation and distension of the smooth endoplasmic reticulum. The activity of testicular beta-glucuronidase was significantly reduced whereas acid phosphatase and sorbitol dehydrogenase activities were unchanged. Plasma testosterone levels were within normal limits. No abnormalities in testicular morphology and biochemistry were seen in animals sacrificed at the end of the first month of thallium exposure. These findings indicate that the male reproductive system is a susceptible target site to toxic effects of thallium under chronic exposure. They also suggest a major involvement of Sertoli cells in the mechanism underlying thallium-induced testicular damage.

Acid Phosphatase↗

Trace of metal exposure in hard metal lung disease.

A male subject exposed for many years to metal dusts from grinding and cutting hard metals was investigated four years after the exposure ceased. While chest x-ray films and histologic examinations showed diffuse interstitial fibrosis and severe perivascular and peribronchiolar fibrosis, radiochemical neutron activation analysis (NAA) showed high W, Ta and Co concentrations in the pulmonary specimen compared to the corresponding determinations in 17 control subjects. Tantalum was also found in high concentrations in bronchoalveolar lavage fluid (BAL) and in the blood. In addition other elements such as Ni, Cr, Th and Cd were found in the lung biopsy specimen of the worker in amounts significantly higher than in the control subjects. The results suggest that hard metal origin of pulmonary fibrosis can be detected many years after removal from exposure.

Adult↗

Retention and tissue binding of titanium in the rat.

The fate of a soluble form of titanium (Ti) was studied in rats injected intraperitoneally with 1 microgram of Ti per rat as [44Ti]ammonium oxalotitanate (IV). After 16 h the Ti concentration in all tissues tested was of the order of 0.5 ng/g wet weight. After 19 days the Ti concentration increased in most tissues, especially in spleen, femur and kidney. By this time 55 ng had been excreted both via urine and faeces and the Ti concentration in blood plasma (mainly associated with plasma proteins) was three times lower than at 16 h postinjection. Chromatographic separation of the day 19 liver cytosol showed the ability of biological macromolecules to incorporate Ti compounds. Ti-labelled 'titanic acid' and 'titanium phosphate' showed low solubility which was, however, higher in human serum than in water and sodium chloride solution. The chromatographic profiles of plasma from incubated human blood in vitro with [44Ti]titanium oxalate showed the capacity of plasma proteins to complex Ti compounds. The results indicated that the long retention of Ti in the body may be due to its ability to form biocomplexes with cellular constituents.

Animals↗

Pathways of Cr (III) and Cr (VI) in the rat after intratracheal administration.

51Cr-labelled Cr3+ and CrO2-4 solutions were administered intratracheally to male rats in doses of 0.1 and 10 micrograms of Cr per rat to evidentiate metabolic differences especially in the lung and in the mechanisms of excretion. Twenty four hours after administration the highest 51Cr amount was present in the lungs for both valency states, being in the Cr (III)-treated group, however, about two times higher. In all other tissues tested the values in the Cr (VI)-treated animals were much higher. Intracellularly, in the Cr (III)-treated group more than 40% of the total lung homogenate was found in the nuclear fraction and only 10% in the cytosol. In the Cr (VI)-treated group 25% was present in the nuclei and more than 50% in the cytosol. Gel filtration 24 h after intratracheal injection showed that in both cytosols chromium was eluted in three peaks including a low-molecular-weight component. Quantitatively, however, the ratios between the 51Cr associated with the three peaks were significantly different between the Cr (III)- and the Cr (VI)-treated animals. This suggests that binding of chromium to low-molecular-weight components should be involved in the passage of this element from the lung to the other tissues. Excretion studies for 7 days showed that after this time the Cr (III)-treated animals excreted about 4% of the dose via urine and more than 36% via faeces, whereas in the Cr (VI)-treated rats the 51Cr was eliminated nearly equally between urine and faeces.

Animals↗

Intestinal absorption and excretion of thallium (201Tl) in the rat.

The gastrointestinal transport of 201Tl-labelled monovalent thallium has been studied in normal and rats with cannulated bile ducts using an in vivo ligated loop technique. A marked difference in the Tl absorptive capacity among the various sections of the gut was observed. 201Tl was taken up more quickly from the colon than from any other segment and the uptake from the ileum and jejunum was higher than from the stomach. In addition, considerable amounts of the intravenously administered thallium were excreted into the intestinal lumen. The biliary excretion was very low compared with the direct transfer of 201Tl across the gastrointestinal wall that occurred against a tissue-to-plasma concentration gradient. In the rat, the large intestine seems to be the major area for the enteral reabsorption and recycling of thallium (I) ions.

Animals↗