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Biomedical subjects

Antonio Mutti

Publications and source records attributed to Antonio Mutti.

At least 37 records · Page 2Linked to original sources
PubMed2005

Determination of dichloromethane, trichloroethylene and perchloroethylene in urine samples by headspace solid phase microextraction gas chromatography-mass spectrometry.

A method for the determination of volatile chlorinated hydrocarbons, namely dichloromethane (DCM), trichloroethylene (TCE), and perchloroethylene (PCE), in urine samples was developed using headspace solid phase microextraction (HS-SPME) gas chromatography-mass spectrometry (GC-MS). HS-SPME was performed using a 75 microm Carboxen-polydimethylsiloxane fiber. Factors, which affect the HS-SPME process, such as adsorption and desorption times, stirring, salting-out effect, and temperature of sampling have been evaluated and optimized. The highest extraction efficiency was obtained when sampling was performed at room temperature (22 degrees C), from samples saturated with salt and under agitation. Linearity of the HS-SPME-GC-MS method was established over four orders of magnitude and the limit of detection was 0.005 microg/l for all the compounds. Precision, calculated as %R.S.D. at three different concentration levels, was within 1-8% for all intra- and inter-day determinations. The method was applied to the quantitative determination of TCE and PCE in human urine samples from exposed (TCE, n=5; median, 9.32 microg/l and PCE, n=39; median, 0.58 microg/l) and non-exposed individuals (n=120; median concentrations, 0.64, 0.22 and 0.11 microg/l for DCM, TCE and PCE, respectively. In addition, two cases of acute accidental exposure to DCM are reported, and the elimination kinetics in blood and urine was followed up. The calculated half-lives of urinary and blood DCM were, respectively, 7.5 and 8.1 h for one subject and 3.8 and 4.3 h for the other.

Adult↗
PubMed2005

Contribution of studies on renal effects of heavy metals and selected organic compounds to our understanding of the progression of chronic nephropathies towards renal failure.

Risk assessment for a number of workplace or environmental chemicals, especially heavy metals and industrial organic compounds, relies mostly on clinical and epidemiologic findings. The low incidence of chronic nephropathies raises methodological issues in carrying out and interpreting human data on the progression of early changes towards end-stage renal disease. To overcome such limitations of epidemiological studies, two main approaches have been explored: (i) human studies relying on biomarkers and (ii) experimental animal models. Animal experiments have been useful to characterize early changes, such as hyperfiltration, eventually leading to chronic renal failure. Animal studies provided insights into the mechanisms underlying microalbuminuria and microproteinuria. Such biomarkers of early changes, developed for use at the workplace, have then been used to monitor such chronic disorders and multifactorial diseases as diabetes and arterial hypertension. Another area where occupational medicine has provided evidence is the effectiveness of primary prevention over other possible approaches. Avoidance of exposure to heavy metals and volatile hydrocarbons and their derivatives, mainly in individuals with diagnosed renal disorders, remains the best approach towards a substantial reduction in the burden of renal diseases.

Animals↗
PubMed2005

Exhaled breath analysis: from occupational to respiratory medicine.

Breath analysis is a technique rapidly gaining ground as a non-invasive tool to diagnose and monitor various aspects of lung diseases. Measurement of exhaled breath is safe, rapid, simple to perform, and effort independent. Given that human breath contains upwards of 250 chemicals, the potential for developing new applications is high. Much of the current knowledge on breath analysis in respiratory medicine derives from years of experience gained in occupational settings, where breath analysis has been used mainly to assess exposure to volatile chemicals. Laboratory based analysis of exhaled air is a complex, expensive and time consuming process and thus is not in wide spread use in occupational medicine. However, recent knowledge of exhaled breath analysis in pulmonology, in particular in bronchial asthma and lung cancer, and the development of fast, and easy to perform non-invasive procedures for breath analysis, re-opened possible application of exhaled breath as a novel approach for biological monitoring of inhaled pneumotoxic substances. The simultaneous quantification of biomarkers of dose and effect in exhaled air may provide new insights into lung damage occurring in workers exposed to inhaled toxicants, thus representing a new and fascinating application in risk assessment strategies.

Breath Tests↗
PubMed2004

Methylmercury cytotoxicity in PC12 cells is mediated by primary glutathione depletion independent of excess reactive oxygen species generation.

Low doses, chronic exposure to mercurial organic compounds is a worldwide health concern and could be pathogenetically relevant as co-factor in several neurodegenerative diseases. In this in vitro study we wanted to further improve our knowledge on the mechanisms of toxicity of methylmercury hydroxide (MeHgOH) in the unprimed PC12 cell line. Cell viability, mitochondrial function, redox state, and cell morphology were recorded at different time points to sequence the events leading to cell death. The lowest cytotoxic concentration and EC50 were 0.3 and 1.3 microM, respectively. 5 microM MeHgOH was fatal for 80% of the cell population after 24 h; within 1 h it caused glutathione (GSH) depletion and a partial dissipation of Deltapsim. At this concentration, reactive oxygen species (ROS) generation was only slight and delayed. After 6h more than 50% of ATP was available and caspase 3 was active. Time-lapse confocal microscopy showed that only a fraction of the cells completed apoptosis while others turned toward necrosis (necrapoptosis). Pre-incubation with N-acetylcysteine (NAC) and GSH but not Cyclosporin A rescued over 80% of the cells. These results provide experimental evidence that, in this cell model, MeHgOH triggers cell death via a primary depletion of GSH but in the absence of ROS overproduction.

Animals↗
PubMed2004

Determination of urinary styrene metabolites in the general Italian population by liquid chromatography-tandem mass spectrometry.

OBJECTIVE: To apply mass spectrometry-based techniques for the determination of background levels of metabolites of widespread organic solvents, such as styrene, in unexposed subjects from the general population. METHODS: The study population consisted of 129 healthy Italian subjects, not occupationally exposed to styrene (67 men; 37% smokers). Urinary levels of mandelic acid (MA) and phenylglyoxylic acid (PGA) were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Using LC-MS/MS, we were able to detect the peaks of MA and PGA in 100% of samples. The distribution of styrene metabolites was log-normal, the geometric means of MA and PGA concentrations being 0.443 mg/g creatinine [geometric standard deviation (GSD) 2.34] and 0.107 mg/g creatinine (GSD 3.49), respectively. The reference intervals estimated for MA and PGA were 0.084-2.339 and 0.009-1.238 mg/g creatinine, respectively. CONCLUSION: The application of highly sensitive and selective mass spectrometry-based analytical techniques could be useful in the definition of reference values for metabolites of organic pollutants and for better assessment of low-level occupational exposure to organic solvents.

Adult↗
PubMed2004

A novel approach based on solid phase microextraction gas chromatography and mass spectrometry to the determination of highly reactive organic compounds in cells cultures: styrene oxide.

A solid phase microextraction (SPME) gas chromatography/mass spectrometry (GC/MS) method was developed to assess actual doses of highly reactive organic compounds like styrene oxide (SO) in exposed cell cultures. Using SPME, we set up a method to measure accurately extracellular SO concentrations as well as to obtain an approximate assessment of intracellular levels. The SPME-GC/MS method was developed and validated using two different coating materials, carboxen-PDMS and polyacrylate. In cell-free systems, linearity was established over 3 orders of magnitude for both fibers, but carboxen-PDMS showed higher extraction efficiency and a lower limit of detection (0.5 x 10(-7) vs 10(-6) M for polyacrylate). Precision calculated as % RSD was within 4-16% for all intra- and interday determinations. Experiments performed to study SO stability in cell-free medium showed a time-dependent decrease in SO concentration (11% of initial the concentration after 24 h), mostly due to the spontaneous hydrolysis of SO into styrene glycol, which was measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS). When the neuronal cell line (SK-N-MC) was exposed to a nominal concentration of 0.3 x 10(-4) M SO, the actual concentration measured in the supernatant was considerably lower and was found to decrease during incubation. Intracellular SO was estimated indirectly, by difference between the amount measured in the medium without cells and in the supernatant of the cell-containing medium.

Acrylates↗
PubMed2004

Cytogenetic markers, DNA single-strand breaks, urinary metabolites, and DNA repair rates in styrene-exposed lamination workers.

The effect of occupational exposure to styrene on frequencies of chromosomal aberrations and binucleated cells with micronuclei and on single-strand break levels in peripheral blood lymphocytes was studied in 86 reinforced plastic workers and 42 control individuals (including 16 maintenance workers with intermittent, low-dose exposure). In these individuals, the irradiation-specific DNA repair rates and the repair rates of 8-oxoguanines were investigated. We assessed the exposure by measuring the concentrations of styrene in air and in blood and of mandelic acid, phenylglyoxylic acid, 4-vinyl phenol conjugates and regioisomeric phenyl hydroxyethyl mercapturic acids in urine. All these parameters correlated with one another. No clear relationship was found between the styrene exposure and the frequencies of chromosomal aberrations. Binucleated cells with micronuclei were moderately related to the parameters of styrene exposure. We found a negative correlation between all exposure parameters and single-strand breaks. The positive correlation between exposure parameters and DNA repair rates suggests that particular DNA repair pathways may be induced by styrene exposure.

Adult↗
PubMed2004

Exhaled breath condensate as a suitable matrix to assess lung dose and effects in workers exposed to cobalt and tungsten.

The aim of the present study was to investigate whether exhaled breath condensate (EBC), a fluid formed by cooling exhaled air, can be used as a suitable matrix to assess target tissue dose and effects of inhaled cobalt and tungsten, using EBC malondialdehyde (MDA) as a biomarker of pulmonary oxidative stress. Thirty-three workers exposed to Co and W in workshops producing either diamond tools or hard-metal mechanical parts participated in this study. Two EBC and urinary samples were collected: one before and one at the end of the work shift. Controls were selected among nonexposed workers. Co, W, and MDA in EBC were analyzed with analytical methods based on mass spectrometric reference techniques. In the EBC from controls, Co was detectable at ultratrace levels, whereas W was undetectable. In exposed workers, EBC Co ranged from a few to several hundred nanomoles per liter. Corresponding W levels ranged from undetectable to several tens of nanomoles per liter. A parallel trend was observed for much higher urinary levels. Both Co and W in biological media were higher at the end of the work shift in comparison with preexposure values. In EBC, MDA levels were increased depending on Co concentration and were enhanced by coexposure to W. Such a correlation between EBC MDA and both Co and W levels was not observed with urinary concentration of either element. These results suggest the potential usefulness of EBC to complete and integrate biomonitoring and health surveillance procedures among workers exposed to mixtures of transition elements and hard metals. Key words: cobalt, exhaled breath condensate, hard metals, lung, malondialdehyde, oxidative stress, tungsten.

Adult↗
PubMed2003

Development of a simplified method for the simultaneous determination of retinol, alpha-tocopherol, and beta-carotene in serum by liquid chromatography-tandem mass spectrometry with atmospheric pressure chemical ionization.

A new and simple method for the determination of fat-soluble vitamins (retinol, alpha-tocopherol, and beta-carotene) in human serum was developed and validated by using liquid chromatography-tandem mass spectrometry with atmospheric pressure chemical ionization (LC-APCI-MS-MS). Different solvent mixtures were tested to obtain deproteinization and extraction of the analytes from the matrix. As a result, a volume of 240 microL of a 1:1 (v/v) ethanol/ethyl acetate mixture added to 60 microL of serum was found to be suitable for both protein precipitation and antioxidants solubilization, giving the best recovery for all three analytes. Deproteinized samples (20 microL) were injected after dilution, without the need for concentration or evaporation to dryness and reconstruction of the sample. Vitamins were separated on a C-8 column using a 95:5 (v/v) methanol/dichloromethane mixture and ionized in the positive-ion mode; detection was performed in the selected-reaction monitoring mode. Linearity of the LC-APCI-MS-MS method was established over 5 orders of magnitude for retinol and alpha-tocopherol, whereas in the case of beta-carotene it was limited to 4 orders. Lower limits of quantitation were 1.7, 2.3, and 4.1 nM for retinol, alpha-tocopherol, and beta-carotene, respectively. Serum concentrations of retinol, alpha-tocopherol, and alpha+beta-carotene determined in a group of healthy volunteers were 2.48, 38.07, and 0.50 microM, respectively, in samples collected in winter ( n=122) and 2.69, 45.88, and 0.90 microM during summer ( n=66).

Adult↗
PubMed2003

Assessment of biotransformation of the arene moiety of styrene in volunteers and occupationally exposed workers.

Styrene is a chemical widely used in the plastic industry. The main pathway of styrene metabolism in humans occurs via the oxidation to styrene-7,8-oxide (7,8-SO). The aim of this study was the investigation of a minor metabolic route, 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 electrospray tandem mass spectrometry (LC-ESI-MS/MS) from 174 workers belonging to three cohorts recruited in European countries and from 26 volunteers exposed to 50 mg/m(3) (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 monophasic 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). Apart from 7,8-SO, 4-VP is the only styrene metabolite not shared with ethylbenzene and therefore thought to be a highly specific marker of styrene exposure. However, 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) and possibly also to the dietary intake of styrene or 4-VP. Consequently, the use of 4-VP as a biomarker of styrene exposure is recommended for exposures exceeding 1 ppm.

Adult↗
PubMed2003

Biomarkers of renal effects in children and adults with low environmental exposure to heavy metals.

The health effects of chronic exposure to heavy metals such as lead, cadmium, and mercury are widely documented, yet few data exist about the renal impact of low environmental exposure to these metals, particularly in children. The aim of this study was to assess renal parameters in children and adults living in an environment known for its past heavy metal contamination around two nonferrous smelters in northern France (Noyelles-Godault and Auby) and to compare their results with age and gender-matched controls living in neighboring municipalities with unpolluted soil (total: 400 children, 600 adults, sex ratio = 1). The integrity of renal function was assessed by measuring the urinary excretion levels of total protein, albumin, transferrin, beta(2)-microglobulin, retinol-binding protein, brush border antigen, and the enzyme N-acetyl-beta-D-glucosaminidase (NAG). The mean blood concentrations of lead (Pb-B, children </=42.2 micro/L, adults </=71.3. micro/L) and of cadmium (Cd-B, children </=0.52 microg/L, adults 0.86 microg/L) were all relatively low, indicating a low uptake of these heavy metals from the environment despite relatively high levels in soil (between 100 and 1700 ppm for lead and 0.7 to 233 ppm for cadmium). Pb-B levels were, however, significantly increased in boys, girls, and women--but not men--living in the polluted area. Boys, men, and women living in the polluted area had also on average higher Cd-B levels. The concentrations of mercury in urine (Hg-U) were by contrast similar in control and exposed groups. None of the renal parameters studied showed a significant difference between control and exposed groups. The influence of heavy metals on renal parameters was further assessed by stepwise multiple regression, testing Pb-B, Cd-B, Hg-U, age, gender, body mass index (BMI), urinary creatinine levels, and area of residence as predictors in both children and adults, including first-order metal interaction terms, smoking habits, and alcohol consumption in adults. The only positive correlation was found between the urinary excretion of NAG activity (standardized for BMI and urinary creatinine) and Cd-B levels when taking the whole children population, indicating that even low cadmium burdens may produce subtle effects on the proximal tubule in children, although deleterious consequences are unlikely should exposure not increase. However, in the absence of other positive findings even after studying the smaller subgroups with higher levels of heavy metals, these results are clearly indicative of the minimal renal impact of living around nonferrous smelters that are currently complying with pollution regulations, even when soil contamination is still high.

Adult↗
PubMed2003

Aldehydes in exhaled breath condensate of patients with chronic obstructive pulmonary disease.

The aims of the present study were (1) to evaluate whether individual aldehydes resulting from lipid peroxidation can be measured in exhaled breath condensate, (2) to assess the influence of sampling procedures on aldehyde concentrations, and (3) to compare aldehyde levels of patients with stable, moderate to severe, chronic obstructive pulmonary disease with those of smoking and nonsmoking control subjects. Aldehydes (malondialdehyde, hexanal, heptanal, and nonanal) were measured by liquid chromatography-tandem mass spectrometry in all samples and overlapping results were obtained by different sampling procedures. Malondialdehyde (57.2 +/- 2.4 nmol/L), hexanal (63.5 +/- 4.4 nmol/L), and heptanal (26.6 +/- 3.9 nmol/L) were increased in patients as compared with nonsmoking control subjects (17.7 +/- 5.5 nmol/L, p < 0.0001; 14.2 +/- 3.5 nmol/L, p = 0.004; and 18.7 +/- 0.9 nmol/L, p = 0.002, respectively). Only malondialdehyde was increased in patients compared with smoking control subjects (35.6 +/- 4.0 nmol/L, p = 0.0007). In conclusion, different classes of aldehydes were identified in exhaled breath condensate of humans. Whereas all aldehydes but nonanal were lower in control subjects as compared with other groups, only malondialdehyde distinguished smoking control subjects from patients with chronic obstructive pulmonary disease and could be envisaged as a biomarker potentially useful to monitor the disease and its response to therapy.

Adult↗
PubMed2003

Genetic polymorphism of drug-metabolizing enzymes and styrene-induced DNA damage.

A cross-sectional study was carried out on 48 workers exposed to styrene and 14 unexposed healthy controls in order to investigate the genotoxic potential of styrene exposure. DNA damage was assessed in peripheral blood leukocytes (WBCs) by the comet assay. Polymorphisms in glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and the gene encoding microsomal epoxide hydrolase (EPHX) were characterized to assess their possible modifying role in styrene metabolism and subsequent DNA damage. Exposed workers showed significantly higher levels of DNA damage compared to controls. Among workers, the GSTM1 and GSTT1 polymorphisms significantly affected comet parameters. Subjects bearing a GSTM1pos genotype showed a significantly higher proportion of damaged nuclei compared to people lacking GSTM1-1 expression (GSTM1null), whereas GSTT1pos workers showed significantly lower DNA damage than GSTT1null individuals. Styrene-7,8-oxide (SO)-induced DNA damage was assessed in vitro in WBCs isolated from the healthy controls. A clear dose-response relationship at micromolar doses of SO was found for the whole group. WBCs collected from subjects bearing the homozygous wildtype GSTP1 genotype showed a significant protection compared to cells from subjects bearing at least one GSTP1 variant allele. The field survey confirms that styrene exposure is associated with increased DNA damage and indicates a modulating role for GSTM1 and GSTT1 genotypes. In vitro experiments suggest that the extent of SO-induced DNA strand breaks depends, at least in part, on interindividual differences in GSH-conjugation capabilities.

Adult↗
PubMed2003

Determination of patterns of biologically relevant aldehydes in exhaled breath condensate of healthy subjects by liquid chromatography/atmospheric chemical ionization tandem mass spectrometry.

A method for the simultaneous determination of several classes of aldehydes in exhaled breath condensate (EBC) was developed using liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry (LC/APCI-MS/MS). EBC is a biological matrix obtained by a relatively new, simple and noninvasive technique and provides an indirect assessment of pulmonary status. The measurement of aldehydes in EBC represents a biomarker of the effect of oxidative stress caused by smoke, disease, or strong oxidants like ozone. Malondialdehyde (MDA), acrolein, alpha,beta-unsaturated hydroxylated aldehydes [namely 4-hydroxyhexenal (4-HHE) and 4-hydroxynonenal (4-HNE)], and saturated aldehydes (n-hexanal, n-heptanal and n-nonanal) were measured in EBC after derivatization with 2,4-dinitrophenylhydrazine (DNPH). Atmospheric pressure chemical ionization of the analytes was obtained in positive-ion mode for MDA, and in negative-ion mode for acrolein, 4-HHE, 4-HNE, and saturated aldehydes. DNPH derivatives were separated on a C18 column using variable proportions of 20 mM aqueous acetic acid and methanol. Linearity was established over 4-5 orders of magnitude and limits of detection were in the 0.3-1.0 nM range. Intra-day and inter-day precision were in the 1.3-9.9% range for all the compounds. MDA, acrolein and n-alkanals were detectable in all EBC samples, whereas the highly reactive 4-HHE and 4-HNE were found in only a few samples. Statistically significant higher concentrations of MDA, acrolein and n-hexanal were found in EBC from smokers.

Air Pressure↗