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Biomedical subjects

A Mutti

Publications and source records attributed to A Mutti.

At least 127 records · Page 7Linked to original sources
PubMed1978

[Relation between environmental concentration, urinary elimination and body burden of chromium in occupationally exposed workers].

Biological and environmental monitoring of chromium exposure was carried out on 20 welders working with special electrodes in the manufacture of tank-cars. The workers were divided in groups, according to the different degree of chromium accumulation, which was determined by renal clearance of diffusible chromium. A closed linear relationship between TWA concentration of hydrosoluble chromium in air and urinary excretion of the metal at the end of exposure was observed. The parameters of regression lines in welders with more (clearance 10 ml/min) or less (clearance 5 ml/min) accumulation of chromium suggest that the renal burden influences not only the basal excretion, but also the excretion at the end of exposure. We underline the difficulty in the determination of correct biological limits if we take them from TLV in air. We must at least consider the degree of accumulation in exposed workers too.

Air Pollutants↗
PubMed1977

[Physiopathological and functional semeiologic considerations in a case of primary normoaldosteronemic hyperaldosteronism].

Among the atypical pictures of primary aldosteronism, sometimes, normal blood and urine concentration of aldosterone have been observed in association with an adrenal aldosterone-producing adenoma. Here we report a case of atypical primary aldosteronism so characterized: -- the patient had the typical clinical findings of aldosteronism (hypertension, hypokalemic alkalosis, polyuria, etc). -- the patient exhibted all the biochemical abnormalities of primary aldosteronism: increase of exchangeable Na and of plasma volume, decrease of exchangeable K, etc. -- the patient had normal blood and urine levels of aldosterone. -- the patient's blood and urine aldosterone concentration increased following sodium depletion and K administration. Such increase was comparable with that obtained in normal subjects after the same tests. However, at the end of these tests, the patient was still in potassium depletion and sodium repletion. Therefore, it was concluded that the secretion of aldosterone, although normal in absolute values, was inappropriate to the metabolic status of the patient, since such "normal" values were found in association with conditions that should have produced an inhibition of aldosterone production. The catheterization of adrenal veins demonstrated the existence of a right adrenal adenoma. The blood pressure and the biochemical parameters of the patients have been normalized by right adrenalectomy.

Adenoma↗
PubMed1977

[Chromium exposure biological indices and clinical findings in chromium plating industry (author's transl)].

According to the investigations carried out on workers of two chromium plating plants, the authors believe that chromium urinary excretion allows to determine the degree of its acute absorption. Moreover, the renal clearance of diffusible chromium allows the evaluation of chromium body burden and is related to the duration as well as to the severity of exposure. This interpretation is supported by the relation between the exposure biological indexes and the clinical and instrumental investigations which make possible the evaluation of lesions caused by chromium exposure, mostly concerning the respiratory system.

Body Burden↗
PubMedDate not supplied

Selective vulnerability of dopaminergic systems to industrial chemicals: risk assessment of related neuroendocrine changes.

Increased serum prolactin (PRL) is a common finding among subjects exposed to styrene, perchloroethylene, lead (Pb), and manganese (Mn) at levels below the current threshold limit values. On a group basis, abnormally high basal PRL shows a dose-related distribution among workers exposed to styrene, Pb, and Mn. On the basis of dose-response relationships, the benchmark doses (BMD) for styrene metabolites in urine, lead in blood (Pb-B), and Mn in urine (Mn-U), are 4 mg/g creatinine, 112 micrograms/L, and 0.3 microgram/L, respectively. Noteworthy, the BMD for Mn-U and Pb-B is well below the upper reference limit. A shift in the distribution but not in the prevalence of abnormally high values of serum PRL was observed among perchloroethylene-exposed dry cleaners, which makes interpretation in terms of risk difficult. The measurement of PRL thus provides opportunities for early identification of excess exposure to neurotoxic chemicals affecting dopaminergic control of pituitary secretion. For styrene, Pb, and Mn the BMD provides an objective and statistically determined threshold, which seems to be in good agreement with the estimated no-observed-adverse-effect-level (NOAEL). The NOAEL, however, is based on traditional approaches that require the application of uncertainty factors, e.g., a default factor of 10 when extrapolating the NOAEL from the lowest-observed-adverse-effect-level (LOAEL). Due to its sensitivity to a number of potential confounders, caution must be exercised when using PRL as a screening test at the individual level. Also, age and sex dependent variations in susceptibility may hamper extrapolations from the occupational settings to the general population.

Biomarkers↗
PubMedDate not supplied

Exposure to hydrocarbons and renal disease: an experimental animal model.

The association between hydrocarbon exposure and chronic glomerulonephritis is still a controversial scientific issue. Recent epidemiological evidence suggests a role of exposure to hydrocarbons in the progression of glomerulonephritis towards chronic renal failure. The present experimental study on rats has been designed to assess the possible role of styrene in the progression of adriamycin (ADR) nephrosis, a well known model of renal fibrosis following nephrotic syndrome induced by ADR. Female Sprague-Dawley rats were exposed to styrene, 300 ppm, 6 h/day, 5 days/week for 12 weeks (group 1); treated with ADR, 2 mg/Kg, i.v., twice on day 1 and day 15 of the study (group 2); Additional groups of animals received both the styrene and ADR treatments (group 3) or served as controls (group 4). The urinary excretion of total and single proteins (albumin, Retinol-Binding Protein (RBP), Clara Cell 16 Kd protein (CC16), fibronectin) was measured monthly, whereas histopathology and determinations requiring blood sampling were carried out at the end of the experiment. A progressive increase in total proteinuria, falling in the nephrotic range already by the 6th week was observed in ADR-treated groups. Styrene exposure caused up to a 3- to 5-fold increase as compared to controls. Co-exposure to ADR and styrene also resulted in a proteinuria much greater than that caused by ADR alone. The interactive effect of styrene and ADR was statistically significant for albuminuria and urinary fibronectin. A similar response was observed for glomerular filtration rate at the end of the experiment, styrene-exposed animals showing hyperfiltration as compared to their respective control group. At the end of the experiment, histopathological scoring for interstitial infiltration and fibrosis was also significantly higher in styrene-treated animals as compared to their respective control groups. In ADR-treated rats, low molecular weight proteinuria (l.m.w.p.) was only slightly affected, suggesting minimal tubular dysfunction associated with extensive tubular atrophy. However, styrene-exposed animals showed l.m.w.p. higher than their respective controls. In summary, in this animal model we were able to confirm both styrene-induced microproteinuria, mainly albuminuria and minor increases in l.m.w.p., observed among occupationally exposed workers and the role of hydrocarbon exposure as a factor accelerating the progression of renal disease suggested by epidemiological investigations in patients suffering from chronic renal disease. Whereas in rats exposed to styrene only, microproteinuria was stable over time and minor histopathological changes were noted at the end of the experiment, evidence of a role of solvent exposure in the progression of ADR nephropathy was obtained in terms of both renal dysfunction and interstitial fibrosis. The mechanistic basis of styrene-ADR interaction is unclear. However, experimental evidence is consistent with epidemiological findings suggesting the need to avoid solvent exposure in patients suffering from renal diseases.

Albuminuria↗
PubMedDate not supplied

Peripheral biomarkers and exposure to manganese.

Biochemical mechanisms underlying manganese (Mn) toxicity include dopamine (DA) auto-oxidation and free radical generation with subsequent neuronal damage. A neuroendocrine approach based on the measurement of serum prolactin (PRL) has been proposed to assess the tonic inhibition of pituitary lactotrope cells by the tubero-infundibular DA system. Low level exposure to Mn oxides in industrial settings is associated with a shift in the distribution of serum PRL towards higher levels as compared to matched controls. The follow-up of a small cohort of workers from a ferro-manganese plant showed that the increased prevalence of abnormally high PRL values is stable over time. Although the mechanistic basis for their application is less straightforward, other biochemical markers such as dopamine beta hydroxylase and monoamine oxidase Type B, have also been assessed. Contrary to PRL levels, these markers cannot be recommended to monitor early biochemical effects of manganese exposure at the workplace. Early biochemical events can be modified by genetically determined individual differences. Owing to the possible role of a reduced capacity of glutathione conjugation as a risk factor increasing the susceptibility to the action of free radicals generated in the presence of Mn, the class mu glutathione S transferase (GSTM1) genotype has also been assessed in workers occupationally exposed. However, the GSTM1 null genotype does not appear to play an important role in the susceptibility to biochemical effects of Mn. A logistic model of the dose-response relationship based on urinary Mn as marker of exposure indicates that the benchmark dose corresponds to Mn levels as low as 0.4 microgram/l. This would imply that environmental exposure to Mn may contribute to abnormally high serum PRL in the general population.

Biomarkers↗
PubMedDate not supplied

[Renal effects of low doses of mercury].

OBJECTIVES: The present study was aimed at investigating early markers of renal damage and dysfunction in subjects exposed to low doses of mercury from different sources. Different groups of subjects were examined with urinary Hg excretion (HgU) ranging from 0.1 to 35.0 micrograms/g creatinine: 122 occupationally exposed workers, 22 subjects living in a non-polluted area, but consuming large amounts of tuna and sword fish, and 197 controls. METHODS: Several markers of renal changes were measured in urine (albumin, fibronectin, beta 2-microglobulin, retinol-binding protein, tubular antigens, N-acetyl-beta-D-glucosaminidase activity) and serum (beta 2-microglobulin and cystatin C). Serum autoantibodies towards collagen, laminin and tubular antigens were assessed in subjects with abnormal renal markers. The role of glutathione-S-tranferases GSTT1 and GSTM1 polymorphisms in the inter-individual variability of biological response to Hg was also investigated. RESULTS: Renal markers were not correlated with HgU. None of such markers differed significantly between exposed workers and controls, except for urinary beta 2-microglobulin, which was decreased in Hg-exposed workers (GM = 55.8 vs 86.6 micrograms/g creatinine), in the absence of any changes in serum concentration. Subjects usually eating tuna and sword fish showed an increased urinary excretion of beta 2-microglobulin, albumin and fibronectin. Serum titres of auto-antibodies did not differ between the groups. Neither in controls nor in exposed workers were the observed differences modified by the GSTM1 and GSTT1 genotypes. CONCLUSION: The present study did not provide evidence of any changes in kidney integrity and function in subjects exposed to very low levels of inorganic Hg resulting in urinary Hg lower than 35 micrograms/g creatinine. Nor did we obtain evidence of Hg-induced autoimmunity towards kidney components. The potential modifying role of GST polymorphisms could not be clarified in the absence of effects associated with exposure to the risk factor, i.e., to inorganic Hg. Preliminary data suggesting nephrotoxic effects of organic Hg from a diet rich in large fish resulting in increased levels of both blood and urinary Hg--which however did not exceed 20 micrograms/g creatinine--deserves further investigation.

Adult↗
PubMedDate not supplied

[Neuroendocrine and neurobehavioral effects associated with exposure to low doses of mercury from habitual consumption of marine fish].

OBJECTIVES: To evaluate neuroendocrine and neurobehavioral effects possibly associated with increased dietary intake of organic mercury (Hg), a group of 22 subjects living on the island of Carloforte (south-west Sardinia) was examined, who were regular consumers of tuna fish with relatively high Hg content. This group, never exposed occupationally to either Hg or to other neurotoxic substances, was compared with 22 age-matched controls employed at a chemical plant in Portotorres (northern Sardinia). METHODS: Hg in urine (HgU) and serum prolactin (PRL) were measured in all cases, whereas measurements of total (HgB) and organic blood mercury were available only for 10 subjects from Carloforte and 6 controls. Data about working history and lifestyle (education, smoking habit, alcohol and sea fish consumption) were collected by an interviewer using a standardised questionnaire. Neurotoxic symptoms were evaluated by a self-administered questionnaire, whereas a test battery, including some computerised tests of the Swedish Performance Evaluation System (SPES) to assess vigilance and psychomotor performance, some tests on motor coordination (Luria-Nebraska and Branches Alternate Movement Task) and one memory test for numbers (Digit Span) was administered to assess neurobehavioral changes associated with exposure to dietary intake of organic mercury. In all cases, characteristics of hand tremor were evaluated by the CATSYS System 7.0. RESULTS: HgU values were significantly higher in the Carloforte group (median 6.5, range 1.8-21.5 micrograms/g creatinine) compared with controls (median 1.5, range 0.5-5.3 micrograms/g creatinine). Serum PRL was significantly higher among subjects from Carloforte and correlated with both urine and blood Hg levels. The scores of each item of the questionnaire investigating neurological symptoms were not statistically different in the two groups. In some tests of the SPES battery (Color Word Vigilance, Digit Symbol and Finger Tapping) the performance of the Carloforte group was significantly worse than that of controls, whereas in the other neurobehavioral tests poorer performances by the Carloforte group were not statistically significant. None of the tremor parameters was significantly different comparing the two groups. Multivariate analysis--controlling for education level and other covariates--carried out for the Symbol-Digit Reaction Time and for the Branches Alternate Movement Task (BAMT) showed that organic Hg concentration in blood was the most significant factor negatively affecting individual performance in these tests. Serum PRL was correlated with some neurobehavioral tests (Digit Symbol, Finger Tapping and BAMT). CONCLUSIONS: Some of the neurobehavioral tests were sensitive enough to discriminate groups with different Hg body burden, even in the low-dose range. However, the pattern of results suggests adverse neurobehavioral effects, especially on psycho-motor coordination, with a significant dose-effect relationship, mostly associated with long-term exposure to low levels of organic mercury due to the usual consumption of large fish with relatively high levels of Hg in the flash.

Adult↗
PubMedDate not supplied

Occupational risk factors for renal cell cancer. An Italian case-control study.

AIM: To examine possible associations between occupational and environmental risk factors and renal cell cancer (RCC), a tumour with unclear aetiology and increasing incidence. METHODS: A questionnaire-based case-control study of 100 histologically verified cases of RCC and 200 controls was conducted at Parma University Hospital. The control group was enrolled from patients attending different outpatient departments and represented the same residential area as the cases. For all exposure variables under study, two levels of duration were defined: "short" and "prolonged" for less than 10 years or more, respectively. RESULTS: The highest risk estimates for RCC were found for "prolonged" exposure to organic solvents with an odds ratio (OR) of 2.2 (95% confidence interval, CI: 1.0-4.8). "Prolonged" exposures to pesticides and copper sulphate were also associated with increased risk, OR 2.0 (95% CI: 0.8-4.7) and OR 2.7 (95% CI: 1.3-5.5), respectively. CONCLUSIONS: Our data suggests an association between RCC and exposure to organic solvents, pesticides and copper sulphate. A risk gradient as a function of exposure duration was found for organic solvents (p = 0.044) and copper sulphate (p = 0.036), but not for pesticides.

Aged↗
PubMedDate not supplied

[In vitro models for the evaluation of the neurotoxicity of methylmercury. Current state of knowledge].

BACKGROUND: In adults, MeHg poisoning is characterized by damage to discrete anatomical areas of the brain (visual cortex, loss of neurons from the granule layer of the cerebellum). However, the immature central nervous system (CNS), which is extremely sensitive to MeHg neurotoxicity, shows a diffuse and widespread damage disorganization of cerebral cortex cytoarchitecture, disappearance of granule cells with narrowing of the molecular layer. While adverse effects have been unequivocally demonstrated in poisoning incidents in humans (visual abnormalities, sensory impairment of the extremities, cerebellar ataxia, hearing loss, muscle weakness, tremor and mental deterioration), the implications of lower level exposures, such as those occurring in fish-eating populations, are still controversial. The high affinity of MeHg for thiol groups makes proteins and peptides bearing cysteines the predominant targets for structural and functional modification by MeHg in all subcellular compartments. METHODS: The identification of MeHg cellular and sub-cellular targets in the CNS is complicated by the fact that it is difficult to observe the outcomes directly in vivo. In neurobiology, in vitro cell culture techniques have been successfully developed and employed to address specific questions of cell biology and nervous system functioning and provide a means to systematically study the complexity of cellular functions of the CNS elements. Moreover, they provide a convenient experimental tool for testing possible functions or postulates in vivo that otherwise might not be conducted. RESULTS: Several mechanisms have been proposed as being implicated in the neurotoxic effects of MeHg. Examples of MeHg molecular effects which may be relevant to risk assessment are presented, including cell death mode, effects on microtubules, calcium signalling, oxidative stress, effects on neurotransmitter systems. CONCLUSIONS: Molecular and cellular approaches permit exploration of early biological responses to chemical or physical agents and definition of the role of these early effects in altered cellular structure and function.

Adult↗
PubMedDate not supplied

[Definition of neurotoxic risk based on the benchmark dose in vitro: illustration with experimental models based on the use of known neurotoxic substances].

The BMD approach has been used to compare the cell viability (MTT assay) of different rat (C6 and PC12, glial and neuronal, respectively) and human cell lines (D384 and SK-N-MC, glial and neuronal, respectively) after 24-h exposure to the following neurotoxic substances: Manganese Chloride (MnCl2), Methyl-mercury (Me-Hg) and the enantiomers of Styrene Oxide (SO). For all rat and human cell lines, the potency of the examined compounds was: MnCl2 < S-SO < R-SO < Me-Hg. A preliminary comparison with in vivo toxicity data for these substances gave rise to consistent results. Whereas a reasonable agreement between in vitro and in vivo data has been found for Mn and styrene oxide, a wide scatter of LOAEL has been reported for Me-Hg and these appear to be either much higher or lower than the BMD for the MTT assay we observed in vitro.

Animals↗
PubMedDate not supplied

[Volatile hydrocarbons in exhaled air: preliminary data on the characteristic profile associated with lung tumors].

The aim of this pilot study was to identify and quantify selected volatile organic compounds (VOCs), such as aliphatic and aromatic hydrocarbons in exhaled air from patients with non small cells lung cancer (NSCLC) as compared to healthy subjects, either smokers or non smokers. Exhaled air has been collected by repeated expirations in Tedlar bags. VOCs were sampled by solid phase micro-extraction (SPME) and analyzed by gascromatography/mass spectometry. NSCLC patients showed higher levels of pentane, 2-metilpentane, 2,4-dimetilheptane in the exhaled air as compared to smokers and non smokers. BTEX (benzene, toluene, etilbenzene and xylenes) concentrations were higher in smokers compared to other groups, whereas no differences were observed between subjects with NSCLC and smokers for heptane and octane. In summary, selected VOCs have sufficient diagnostic power to differentiate among the three groups we examined. These differences might be exploited to identify characteristic fingerprints of various lung diseases.

Adult↗
PubMedDate not supplied

[Urinary excretion of 4-vinyl phenol after experimental and occupational exposure to styrene].

Aim of this study was to assess the importance and the role of a minor metabolic route of styrene metabolism, involving the oxidation of the arene moiety of styrene, by means of the characterization of the conjugated urinary metabolites of 4-vinylphenol (4-VP). 4-vinylphenol-glucuronide (4-VP-G) and -sulfate (4-VP-S) were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) from 174 workers belonging to three cohorts recruited in European countries, and from 26 volunteers exposed to 50 mg/m3 (11.8 ppm) of styrene for 8 h. The 4-VP conjugates represented about 0.5-1% of the total excretion of styrene metabolites. Both 4-VP-G and 4-VP-S are eliminated with a mono-phasic kinetic, the glucuronide being excreted faster (half-time, 2.2 +/- 0.2 h) than the sulfate (half-time 9.7 +/- 1.7 h). The urinary 4-VP was found to be significantly correlated both with airborne styrene (r = 0.607, p < 0.001) and the sum of MA and PGA (r = 0.903, p < 0.001 in 'end-of-shift' samples). A measurable background excretion of 4-VP was also found in all urine samples from controls not occupationally exposed to styrene. This background appears to be highly correlated to smoking (p < 0.001). Consequently, the use of 4-VP as a biomarker of styrene exposure is recommended for exposures exceeding 1 ppm.

Adult↗
PubMedDate not supplied

[Genetic polymorphism of biotransforming enzymes and genotoxic effects of styrenes].

A cross-sectional study was carried out on laminators producing glass-fibre reinforced plastics, to evaluate the role of genetic polymorphism of xenobiotic metabolising enzymes on the genotoxicity of styrene. Clastogenic effects, evaluated by the micronucleus test, are related with end-of-shift urinary concentration of 4-vinylphenol and seem to be modulated by NQO1 polymorphism; aneuploidogenic effects, evaluated by the identification of centromers in micronuclei using the fluorescence in situ hybridisation technique with a pancentromeric probe, are related with before-shift urinary levels of mandelic and phenylglyoxylic acids and seem to be modulated by the GSTM1 polymorphism.

Adult↗