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Biomedical subjects

L Soleo

Publications and source records attributed to L Soleo.

At least 19 recordsLinked to original sources

Needs, education and accreditation in occupational medicine in Italy.

In Europe, continuing medical education is one of the main instruments for improving physicians' performance and ensuring adequate health care for citizens. Recent regulations have made such continuing education compulsory in Italy. Considering the particular features of occupational medicine, the Italian Society of Industrial Medicine and Industrial Hygiene (S.I.M.L.I.I.) recently set up a specific education and accreditation programme for occupational physicians, called the "Excellence Accreditation Scheme". The programme is based on the findings of a survey among occupational physicians, carried out in collaboration with the National Institute of Occupational Safety and Prevention (I.S.P.E.S.L.), which enquired into their training and continuing education needs. The programme started in 2003, and its first edition-presented here-involved more than 400 physicians specialising in occupational health.

Accreditation↗

Biological monitoring in occupational exposure to low levels of 1,3-butadiene.

Exposure to 1,3-butadiene (BD), a probable carcinogen to humans, was investigated in two groups of subjects working in a petrochemical plant where BD is produced and used to prepare polymers: 42 occupationally exposed workers and 43 internal non-occupationally exposed controls. BD personal exposure was very low but significantly different in the two groups (median airborne BD 1.5 and 0.4 microg/m(3) in exposed and controls, respectively). Similarly, BD in blood and urine, but not in exhaled air, was higher in the exposed workers than in controls (blood BD 3.7 ng/l versus <1.8 ng/l, urinary BD 2.4 ng/l versus <1.0 ng/l). These three biomarkers correlated significantly with personal exposure ( 0.283 < or = Pearson's r < or = 0.383) and between them (0.780 < or = r < or = 0.896). Excretion of urinary mercapturic acids N-acetyl-S-(3,4-hydroxybutyl)-l-cysteine (MI), N-acetyl-S-(1-hydroxymethyl-2-propenyl)-l-cysteine and N-acetyl-S-(2-hydroxy-3-butenyl)-l-cysteine (MII), chromosomal aberrations (CA), and sister chromatid exchanges (SCE) in peripheral blood lymphocytes were not influenced by occupational exposure. Our results show that unmetabolised BD in biological fluids, and particularly urinary BD, represents the biomarker of choice for assessing occupational exposure to low airborne concentrations of BD.

Acetylcysteine↗

Determination of urinary S-phenylmercapturic acid by liquid chromatography-tandem mass spectrometry.

Urinary S-phenylmercapturic acid (S-PMA) is considered a useful biomarker for the measurement of low levels of benzene exposure, related to occupational exposure, smoking habits or environmental pollution. S-PMA quantitative analysis requires highly sensitive and specific techniques and purification procedures, mainly based on liquid-liquid or solid-phase extraction, which result in time expensive analyses. A method was developed for the quantitative determination of S-PMA in urine by using a simple, reproducible and easily automatizable HPLC purification followed by LC/ESI-NI/MS2 analysis. In order to reduce the cost of the analysis, related to the use of expensive labeled standards, p-bromo-S-phenylmercapturic acid (p-Br-S-PMA) was synthesized, characterized and used as internal standard. The feasibility and efficacy of the proposed method were examined by constructing calibration curves in the range from 6.2 to 200 microg/l and data were analyzed in terms of linearity and statistical parameters. The detection limit, related to the purification of 1 ml urine sample is 5 microg/l. The method was applied to the analysis of 12 urine samples from smoker subjects non-occupationally exposed to benzene. S-PMA urinary levels ranged from 13.6 to >200 microg/l, suggesting a high influence of life style in the S-PMA excretion. The proposed analytical method is suitable for the biological monitoring of both smoker and non-smoker workers, occupationally exposed to benzene. By processing at least 2 ml of urine samples, the method appears to be also useful for the evaluation of benzene uptake due to the environmental pollution.

Acetylcysteine↗

Effect of shift work on body mass index: results of a study performed in 319 glucose-tolerant men working in a Southern Italian industry.

OBJECTIVE: To examine the influence of shift work on metabolic and cardiovascular risk factors in subjects working in an industry sited in Apulia, Southern Italy. DESIGN: Cross-sectional study of metabolic effects of shift work in glucose tolerant workers in a chemical industry in southern Italy. SUBJECTS: The subjects included 319 glucose tolerant male individuals, aged 35-60 y. MEASUREMENTS: Anthropometric parameters (body mass index (BMI) and waist-to-hip ratio (WHR)), fasting concentrations of glucose, insulin, and lipids (total cholesterol, HDL-cholesterol, triglycerides), the sum of glucose levels during 75 g-oral glucose tolerance test (Sigma-OGTT), and systolic and diastolic blood pressure (SBP and DBP, respectively). RESULTS: The prevalence of obesity was higher among shift workers compared to day workers, whereas body fat distribution was not different between the two groups. Shift workers had higher BMI than day workers, and shift working was associated with BMI, independently of age and work duration. Shift workers had significantly higher SBP levels, which were independently influenced by BMI, but not by shift work, thus suggesting that the difference in SBP may well be mediated by the increased body fatness. CONCLUSION: In workers of an industry sited in Southern Italy, shift work may be directly responsible for increased body fatness and is indirectly associated with higher blood pressure levels and some features of metabolic syndrome.

Adult↗

Assessment of reference values for mercury in urine: the results of an Italian polycentric study.

The results of a polycentric study to assess the reference values of urinary mercury (U-Hg) in four Italian cities are presented. A total of 383 subjects were selected on the basis of standardised criteria by a questionnaire on personal habits, lifestyle, occupational or non-occupational exposure to Hg, medical history, number and area of dental amalgams. U-Hg was determined by hydride generation atomic absorption method (HG-AAS), with a detection limit of 0.5 microg/l and by flow injection (FI) inductively coupled plasma mass spectrometry (ICP-MS), with a detection limit of 0.03 microg/l. The median value of U-Hg, determined by HG-AAS, was 0.78 microg/g creatinine (0.75 for males and 0.83 for females), with 5 degrees and 95 degrees percentiles, respectively, of 0.17 and 3.66 microg/g creatinine. When determined by FI ICP-MS, the median value was 0.79 microg/g creatinine (0.77 for males and 0.79 for females) with 5 degrees and 95 degrees percentiles of, respectively, 0.12 and 5.02 microg/g creatinine. Among the independent variables, city of origin, area of dental amalgams, fish intake and tobacco smoking significantly influenced the U-Hg levels. The U-Hg reference values from this survey are lower than those from other recent investigations, probably due to characteristics and selection of the examined individuals and to the strict control of pre-analytical and analytical factors of variability.

Adult↗

Blood lead reference values: the results of an Italian polycentric study.

This paper presents the results of a polycentric study carried out in seven different areas, organized by the Italian Society of Reference Values (SIVR) for assessing reference values of lead in blood (B-Pb) at the current doses of the metal to general population. The estimated arithmetic mean for B-Pb in males was of 45.1 microg/l and 30.6 microg/l in females; the 95th centile was 100 and 60 for males and females, respectively. The main variables influencing B-Pb levels were gender, age, BMI, outside sport practice, alcohol consumption and smoking habits, while the geographic area and the urban residence did not affect the metal concentration in blood.

Adolescent↗

Hemoglobin adducts as biomarkers of 1,3-butadiene in occupationally low exposed Italian workers and a few diesel-exposed miners.

Hemoglobin adducts were determined as biomarkers of 1,3-butadiene (BD) in 30 workers and 10 controls from an Italian BD plant and in 14 diesel-exposed miners. N-(2,3,4-trihydroxybutyl)valine (THBVal), an N-terminal valine globin adduct of reactive butadiene metabolites, was analyzed by gas chromatography/high resolution mass spectrometry after a modified Edman degradation and further acetylation. The BD exposure for the plant workers was 31 microg/m(3) (personal sampling). Whereas there was no detectable difference in hemoglobin adduct levels (range 17.7-61.4 pmol/g globin) between the total group of exposed and controls, slight but significant differences could be found between two subgroups of workers from different production units as well as one subgroup and controls (P<0.05), between smoking (n=13) and non-smoking exposed workers (n=17; P=0.066) as well as between smoking exposed workers and controls (P=0.055). Adduct levels of the miners (all non-smokers) were in the same range as those of the Italian BD-workers and controls. The internal exposure and strain measured by THBVal levels resulting from a very low occupational BD exposure was in the range of the contribution of moderate smoking.

Biomarkers↗

In vitro inhibition of thymulin production in mercury-exposed thymus of young mice.

Lymphocyte differentiation, maturation and peripheral functions are affected by the thymic protein hormone thymulin. Mercury at very low concentrations has been seen to impair some lymphocytic functions causing subclinical manifestations in exposed workers. The present study was performed to test in vitro the effect of mercury on the production kinetics of thymulin using cultures of whole thymuses from young mice. Exposure to mercury (10(-8) M and 10(-6) M) added to the cultures, reduced kinetic thymulin production at all time intervals considered (1, 2, 4, 5 and 6 h) as compared to kinetic thymulin production of thymuses from young control mice. After the first hour the inhibition is more evident at the highest mercury concentration. Thymulin production decreased by 70, 74, 82 and 86% and by 55, 66, 73 and 81% for mercury concentrations of 10(-6) M and 10(-8) M, respectively, after 2, 4, 5 and 6 h. Mercury toxic effect on thymulin kinetics may be directly exerted to thymulin synthesis in epithelial cells, although it is less dramatic than that of cycloheximide (CHX), known as a potent inhibitor of protein synthesis in such cells. The toxic effect of mercury on thymic endocrine activity might cause the subclinical effects on cell-mediated immunological status observed in mercury exposed workers.

Animals↗

Monocyte-macrophage system and polymorphonuclear leukocytes in workers exposed to low levels of metallic mercury.

Our previous research (Soleo L, Vacca A, Vimercati L et al. Occup Environ Med 1997;54:437-442) showed a reduction in tumor necrosis factor-alpha (TNF-alpha) serum levels in workers with prolonged exposure to low doses of inorganic mercury, suggesting an in vivo functional defect of the monocyte-macrophage system. On this basis, here we wondered whether workers exposed to lower doses of metallic mercury displayed possible changes in the monocyte-macrophage system. In this particular cohort of workers, we also sought for the effects of the exposure on the polymorphonuclear leukocytes (PMNL) chemotaxis. The monocyte-macrophage system and the natural killer (NK) cells were examined in 19 exposed workers and in 25 unexposed workers, as the control group (controls). Specifically, the circulating monocyte-macrophage cells and their CD13, CD15 and CD33 subsets, serum cytokines (IL-8, GM-CSF and TNF-alpha) and the NK cells were analyzed. In seven exposed and seven controls randomly chosen workers the PMNL chemotaxis was also assessed. The selected indicator of mercury exposure were the levels of mercury in the urine (U-Hg), that was significantly higher in exposed workers than the controls (9.7 +/- 5.5 microg/l and 2.4 +/- 1.2 microg/l, respectively). None of the exposed workers had shown signs of either acute or chronic inorganic mercury toxicity or any form of hypersensitivity. Several immunological variables tested, monocyte-macrophage cells and their subsets, NK cells and serum cytokines overlapped between the exposed and the control workers. When the workers were considered as a whole (exposed plus controls), no correlation was found between current U-Hg and all immunological parameters. However, when exposed workers were studied separately, an inverse correlation was disclosed between cumulative U-Hg and cells (as percentage) expressing the CD13 (r = -0.599; P = 0.007) and CD15 (r = -0.614; P = 0.005) molecules, and NK cells (r = -0.455; P = 0.05). Moreover, a significant impairment in the PMNL chemotaxis (t = 3.70; P = 0.003) was observed in the exposed workers. The results of our study suggest that the exposure to very low levels of metallic mercury led to subtle impairment of circulating monocyte and NK cells (as percentages) according to the increase in U-Hg levels, as well as of the PMNL chemotactic function in this particular group of workers, even though they remain clinically asymptomatic. Therefore, we suggest that impairment of these parameters provide a sensitive indicator of metallic mercury and other chemical contaminants present in the environment.

Adult↗

Mass spectrometric identification of a candidate biomarker peptide from the in vitro interaction of epichlorohydrin with red blood cells.

The reaction products of epichlorohydrin with human alpha- and beta- globins, obtained through in vitro incubation of these compounds and red blood cells, were determined by using reversed-phase high-performance liquid chromatography (RP-HPLC), electrospray ionization mass spectrometry and matrix-assisted laser desorption/ionization tandem mass spectrometry. The alpha-globin was much more reactive than the beta-globin. At low incubation ratios, approximating the order of magnitude of epichlorohydrin concentration as found in workplaces, the only modified peptide still detectable was the 62-90 belonging to the alpha-chain and carrying an incremental mass of 92 u on either His72 or His89. Given that the two peptides co-eluted in a single chromatographic peak during RP-HPLC separation, they could be chosen as suitable biomarkers for quantification in the setting up of a new methodology for the biological monitoring of persons occupationally exposed, replacing currently known procedures.

Amino Acids↗

A novel approach for identification and measurement of hemoglobin adducts with 1,2,3,4-diepoxybutane by liquid chromatography/electrospray ionisation mass spectrometry and matrix-assisted laser desorption/ionisation tandem mass spectrometry.

The structural characterisation of the adducts formed by in vitro interaction of hemoglobin (Hb) with 1,2,3,4-diepoxybutane (DEB), the most reactive 1,3-butadiene (BD) metabolite, was obtained by liquid chromatography/electrospray ionisation mass spectrometry (LC/ES-MS) analysis of modified tryptic peptides of human hemoglobin chains. The reactive sites of human hemoglobin towards DEB and its hydroxylated derivatives (trihydroxybutyl (THB)-derivatives) were identified through the characterisation of alkylated tryptic peptides by matrix-assisted laser desorption/ionisation tandem mass spectrometry (MALDI-MS/MS). Based on this characterisation, a procedure was set up to measure the Hb-adducts of THB-derivatives by isotope dilution mass spectrometry with the use of a deuterated peptide standard. The results obtained here could permit optimisation of molecular dosimetry of BD-adducts, and extension of the analysis to the biological monitoring of occupational exposure to butadiene.

Alkylation↗

Increment of sister chromatid exchange frequencies (SCE) due to epichlorohydrin (ECH) in vitro treatment in human lymphocytes.

Although several studies have examined the effects on health of exposure to epichlorohydrin (ECH) through normal industrial operations and production, there is still considerable interest in its potential harmful effects on humans. The aim of the present study was to evaluate ECH effects in vitro through controlled investigations by using sister chromatid exchange (SCE), micronucleus (MN), and chromosome aberrations (CA) as the test battery. Cultures for cytogenetic tests were set up from blood samples of four healthy non-smoking and three smoking males. The experiments were performed using four different concentrations: 10(-10) M, 10(-8) M, 10(-6) M, and 10(-4) M, of ECH in DMSO. Analysis of variance showed that concentrations of ECH had significant effects on SCE/cell frequencies in the lymphocyte cultures of all donors (F=100.25, P<0.001). We were unable to find any evidence of significant increases in CA and MN frequencies in ECH-treated lymphocyte cultures with respect to the controls.

Adult↗

Auditory dysfunction in occupational noise exposed workers.

Occupational noise-induced hearing loss (NIHL) is well known to be an epidemiologically relevant problem. The subjects affected with NIHL show alteration of hearing thresholds as well as a worsening of the cochlear analysis functions and, usually, an impaired speech discrimination in presence of background noise. The study has evaluated the relationships between hearing threshold and equivalent exposure lever per day (Lepd), age and working seniority in a homogeneous sample of occupationally noise exposed workers. Three subgroups were also selected to study the most important cochlear functions as well as nerve and central functions. The first subgroup (Nn) contained normal hearing workers exposed to non-hazardous noise, while the second (Bn) contained workers exposed to high level continuous noise during their work day without clinical evidence of NIHL. The third subgroup (Bd) included subjects affected with the typical 4 kHz notch exposed to the same noise conditions than subgroup Bn. The results show that the hearing impaired subjects have the worst overall cochlear performance; however also the normal hearing workers exposed to hazardous noise have worse performance than subgroup Nn, relatively to high frequency thresholds, frequency resolution, TEOAEs, DPOAEs, stapedial acoustic reflex dynamic parameters. The results suggest that these measures could be used in the monitoring of the NIHL as indicators of subtle alterations of the hearing function.

Acoustic Impedance Tests↗

Minimal immunological effects on workers with prolonged low exposure to inorganic mercury.

OBJECTIVES: This study was carried out to investigate possible immunological changes in workers with prolonged low exposure to inorganic mercury in a fluorescent light bulb factory. METHODS: 29 immunological variables were examined in 34 workers with prolonged low level exposure to inorganic mercury (exposed workers) and 35 unexposed workers as the controls. The selected indicator of mercury exposure was concentration of mercury in the urine (U-Hg), which declined progressively from 36.0 micrograms/l in 1978 to 6.0 micrograms/l in the study year 1994. RESULTS: None of the exposed workers had ever shown signs of either acute or chronic inorganic mercury toxicity or had shown any form of hypersensitivity. The only changes found in the exposed workers, compared with the controls, were a reduction of the cells that express cluster differentiation (CD25,(T activation antigen (Tac antigen))) and concentrations of tumour necrosis factor-alpha (TNF-alpha) in serum. However, the decrease of cells that express CD25 was unrelated to occupational exposure and was, in all likelihood a chance finding. Conversely, the decline in serum TNF-alpha was closely associated with occupational exposure. However, no dose-response relation was found between U-Hg and TNF-alpha concentrations; nor were TNF-alpha concentrations affected by cumulative occupational exposure to inorganic mercury in over 20 years. CONCLUSIONS: Tentatively, we suggest that reduced serum TNF-alpha concentrations might be indicative of an in vivo functional defect of the monocyte macrophage system in this particular group of workers even though they were clinically asymptomatic.

Biomarkers↗

Acute radiodermatitis from accidental overexposure to X-rays.

Approximately 2 weeks after accidental overexposure to X-ray radiation, a worker developed acute radiodermatitis on fingers of both hands. Exposure simulation indicated that total ionizing radiation absorbed by his fingers amounted to about 20 Gy. After 2 years, acute radiodermatitis evolved to chronicity of lesions with presence of atrophic skin, teleangiectasia, alopecia, and dyskeratosis on three right-hand fingers. Cytogenetic dosimetry of peripheral blood lymphocytes, performed 2 months after acute radiation, showed an increase of micronuclei (7% vs. 1 +/- 0.4% according to laboratory reference data). The increase was ascribed to the high dose of ionizing radiation absorbed by circulating lymphocytes in the vessels of overexposed tissues. The cytogenetic examination was repeated 27 months after acute irradiation; it was found that the percentage of micronuclei had been restored to within reference levels. The possibility of using cytogenetic dosimetry, following acute partial exposure to X-rays, not just as an indicator of previous exposure, but also as an indicator of the absorbed radiation dose is examined. Lastly, the possible stochastic effects that may set in on the skin of the affected fingers and the need for periodically monitoring the evolution of chronic skin lesions, are discussed.

Absorption↗

Toxicity of fungicides containing ethylene-bis-dithiocarbamate in serumless dissociated mesencephalic-striatal primary coculture.

Agricultural exposure to the organomanganese fungicide MANEB (manganese-ethylene-bis-dithiocarbamate) may induce an extrapyramidal syndrome resembling parkinsonism. To evaluate the relative role of manganese (Mn) and ethylene-bis-dithiocarbamate (EBDTC) in the hazard of organomanganese fungicides, we studied the effects of MANCOZEB (Mn-Zinc-EBDTC) and ZINEB (Zinc-EBDTC) on serumless dissociated mesencephalic-striatal primary coculture. High affinity 3H-dopamine (DA) and 14C GABA uptakes as well as immunocytochemical staining of tyrosine hydroxylase (TH)-containing cells were used as specific functional markers of DA and GABA neuron viability. Both MANCOZEB and ZINEB, at 10 and 50 microM concentrations, dose dependently reduced DA and GABA viability parameters. These data suggest that EBDTC rather than Mn may be primarily responsible for the cytotoxicity of organomanganese fungicides on neuronal systems relevant to the pathophysiology of parkinsonism.

Animals↗

Manganese toxicity in serumless dissociated mesencephalic and striatal primary culture.

Exposure to elevated levels of Manganese (Mn) can result in an irreversible brain disease characterized by extrapyramidal signs and symptoms resembling Parkinson's disease. To identify the neuronal target of Mn neurotoxicity, MnCl2 was added to serumless dissociated mesencephalic-striatal cultures from rat embryo on day 4 in vitro. High affinity 3H-dopamine (DA) and 14C-GABA uptakes were assessed as specific functional markers of DAergic and GABAergic cell viability, respectively. After 60-min exposure, MnCl2 at 0-200 microM did not modify the morphologic appearance of the cultures, specific DA and GABA uptakes, or the number of DA neurons visualized by immuno-cytochemical staining with tyrosine hydroxylase. In contrast, culture exposure to 20 microM MnCl2 for 24 h selectively reduced specific GABA uptake without affecting specific DA uptake or the number of DA neurons. The exposure to a higher MnCl2 concentration was accompanied by signs of general toxicity. Striatal GABA neurons seemed to be more susceptible to Mn toxicity than mesencephalic GABA neurons. Overall, our data suggest that striatal neurons rather than mesencephalic DA neurons may be the main target of Mn neurotoxicity.

Animals↗

Occupational sensitization to epoxy resin and reactive diluents in marble workers.

10 out of 22 marble workers handling a bicomponent resin, based on epoxy resin and ortho-cresyl glycidyl ether (CGE), developed contact dermatitis and airborne contact dermatitis within 20 days to 2 months of exposure. All 22 subjects were patch tested with epoxy resin, bisphenol A, epichlorohydrin and a series of reactive diluents. The 10 symptomatic subjects were all positive to the reactive diluent CGE, and 4 of them also to epoxy resin. The other reactive diluents that gave positive reactions were phenyl glycidyl ether (7 cases), cyclohexanedimethanol glycidyl ether (2 cases), 1,6-hexanediol diglycidyl ether (2 cases) and allyl glycidyl ether (1 case). The findings of our study suggest that allergic potential is directly proportional to the electronic charge available, for all electron-rich molecules (solvents, high and low polymers, reagents) that interact with the glycidyl ether group. Lesser, but still noticeable, effects are detected when activation of the glycidyl group is related to the possible formation of intramolecular hydrogen bonds. In practice, the occupational problem was partly solved by changing the type of glycidyl ether.

Adult↗