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Biomedical subjects

A Cavalleri

Publications and source records attributed to A Cavalleri.

At least 19 recordsLinked to original sources

Urinary excretion of specific mercapturic acids in workers exposed to styrene.

Styrene is an important chemical of wide industrial use, particularly in the manufacture of polymers and reinforced plastics. Environmental and occupational exposures to styrene occur predominantly via inhalation. Styrene undergoes biotransformation mainly by side chain oxidation catalyzed by cytochrome P-450 enzymes to its reactive metabolite, styrene oxide. The (R)- and (S)-enantiomers of styrene oxide can be conjugated with glutathione to both (R)- and (S)-diastereoisomers of specific mercapturic acids, N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (M2). We conducted this biomonitoring study with the aim of evaluating the association between excretion of specific mercapturic acids (M1 and M2) and level of exposure to styrene among occupationally exposed people. The mean time-weighted average (TWA) exposure was about one-half the current threshold limit value, the range of the values varied from 44 to 228 mg/m3. Geometric mean (GM) concentrations of 650, 1,084, and 31.8 micrograms/g creatinine were measured, respectively, for M1-S, M2, and M1-R. The environmental styrene concentration exhibited a significant correlation with total specific mercapturic acid (Mtot = sum of M1-R, M1-S, and M2), making it possible for the first time to calculate the approximate relationship between styrene uptake and excretion of these substances. The M2 mercapturic acid had a better correlation (r = 0.56) with respect to M1-R and M1-S. Significant correlations were found also between the excretion of specific mercapturic acids and biological exposure indices (i.e., mandelic and phenylglyoxylic acids and urinary styrene).

Acetylcysteine

Color vision loss among styrene-exposed workers neurotoxicological threshold assessment.

Styrene represents nowadays one of the most used organic solvent. The current exposure limit proposed for this chemical differs significantly from country to country: the Threshold Limit Value-Time Weighted Average (TLV-TWA) proposed by the American Conference of Governmental Industrial Hygienists (ACGIH) is 50 ppm while the German, Finnish and Swedish occupational exposure limit is 20 ppm. Nevertheless, effects on the nervous system were recently reported in workers exposed at TWA styrene levels below the current TLV. Neuro-optic pathways have been shown to be particularly vulnerable to organic solvent exposure. Analysis and measurements of visual functions can provide important information on early neurotoxic effects. Previous studies support the hypothesis that styrene exposure can induce a dose-dependent color vision loss. The aim of this study is to assess a threshold level below which no detectable effect occurs for color vision. We applied a sub-application of the change point problem in two-phase regression considering one phase as a constant line. In accordance with this model the maximum-likelihood technique was used as a method to examine the dose- effect relationship between external styrene exposure and chromatic discrimination. The present article presents a joint analysis of data from two previously published studies, one carried out in Canada and the other in Italy. The age and seniority of the workers from both countries were remarkably similar, as were the process type, the chemicals used and the work-tasks of exposed subjects. The mathematical method presented here shows the existence of a statistically significant threshold. This finding shows that, in fiberglass-reinforced plastics industry, visual color impairment could be significantly detected above 4 ppm (upper limit of the confidence interval at 5% = 26 ppm). The exact clinical meaning of this effect, and also the progress of the impairment in exposed workers, is still to be assessed in further studies. The results of our study support the need of a reduction of the occupational limits for styrene in workplaces to values close to or lower than German, Finnish or Swedish exposure limits.

Adult

Methods for urinary testosterone analysis.

Urinary testosterone analysis requires a multistep procedure to achieve a good degree of sensitivity and specificity in the dosage. Hydrolysis, extraction, purification and quantification are usually performed in sequence, and several options can be chosen for each of them. After introductory remarks on the applications of urinary testosterone measurement and a short description of the metabolic pathway of the hormone, an overview of the techniques most commonly used in each step is presented. Advantages and disadvantages of each of them are outlined, and a procedure for urinary testosterone analysis is suggested. The procedure consists of: enzymatic hydrolysis with Helix pomatia juice, followed by solid-phase extraction of hydrolyzed urine by a C18 cartridge coupled with an NH2 cartridge and high-performance liquid chromatography cleanup of the extract. Then, quantification can be achieved by gas chromatography or radioimmunoassay.

Chromatography, Affinity

Colour vision loss in workers exposed to elemental mercury vapour.

We evaluated colour vision in 33 workers exposed to elemental mercury (Hg) vapour and in 33 referents matched for sex, age, alcohol consumption and cigarette smoking. The results were expressed as colour confusion index (CCI). In the workers urinary excretion of Hg (HgU) ranged from 28 to 287 micrograms/g creatinine. Subclinical colour vision loss, mainly in the blue-yellow range, was observed in the workers. This effect was related to exposure, as indicated by the correlation between HgU and CCI (r = 0.488, P < 0.01). In the workers whose HgU exceeded 50 micrograms/g creatinine, mean CCI was significantly increased compared to the matched referents. The results suggest that exposure to elemental Hg inducing HgU values exceeding 50 micrograms/g creatinine can induce a dose-related colour vision loss.

Adult

Testosterone, dihydrotestosterone and oestradiol levels in postmenopausal breast cancer tissues.

The ability of breast tumours to synthesize hormones is well recognized, and local production of sex steroids is thought to play a role in breast cancer growth. We measured the intratumour and circulating levels of testosterone, dihydrotestosterone (DHT) and oestradiol in 35 histologically confirmed carcinomatous mammary tissues obtained at breast surgery from 34 postmenopausal patients, age 50-85 years. Intra-tissue steroids were extracted with ethanol:acetone (1:1; v/v), defatted with 70% methanol in water, and extracted with ether. Steroids, from tissue and serum, were separated by partition chromatography on celite columns and were measured by RIA. Intratumour testosterone and DHT concentrations were significantly correlated, after the exclusion of an outlier (rs = 0.71; P = 0.0001). No association was found between oestradiol and either of the two androgens. Mean oestradiol and DHT concentrations were significantly higher in tissue than in blood (P = 0.0001). Mean testosterone levels in tissues did not significantly differ from those measured in blood. Our data suggest that at least a part of intratissue DHT is produced locally from testosterone. The meaning of high oestradiol and DHT levels in cancer tissue still needs to be defined.

Aged

Perchloroethylene exposure can induce colour vision loss.

We evaluated colour vision in 35 dry-cleaners exposed to perchloroethylene (PCE) and in a paired number of controls matched for sex, age, alcohol consumption and cigarette smoking. A subclinical colour vision loss, mainly in the blue-yellow range, was present in dry-cleaners. This effect was related to PCE exposure levels, and appeared at environmental concentrations of the solvent well below the current exposure limits for exposed workers. The results suggest that PCE exposure, even at low environmental levels, can induce a dose-related impairment of colour vision.

Adult

Testosterone levels as a marker of prognosis to goserelin treatment in metastatic breast cancer.

Testosterone levels were measured in blood and urine of 35 premenopausal metastatic breast cancer patients before starting therapy with the gonadotrophin-releasing hormone (GnRH) analogue, goserelin. The aim of the study was to verify the reliability of testosterone measurement as a marker of prognosis. The time interval between starting therapy and progressive disease (time to progression) was chosen to assess prognosis. Univariate and multivariate analysis showed that only urinary testosterone levels were significantly associated with time to progression (Wald test 6.66, P = 0.01 for univariate and Wald test 7.93, P = 0.0049 for multivariate analysis), whereas no association was found for testosterone in blood. A statistical model is proposed to evaluate probability of progressive disease in relation to testosterone values in urine at different times. According to the model, the probability of progression decreases with increasing urinary testosterone values.

Adult

Urinary styrene in the biological monitoring of styrene exposure.

The urinary excretion of styrene represents a promising indicator of exposure to this solvent. Nevertheless extensive research under field conditions is scant. In this investigation 214 styrene-exposed workers from 10 fiberglass-reinforced plastics factories were studied. Environmental monitoring was performed by personal passive sampling. Blood styrene and the urinary excretion of styrene and its main metabolites, mandelic acid (MA) and phenylglyoxylic acid (PGA), were measured. The correlation coefficient between the time-weighted average of environmental styrene and the mean urinary excretion of styrene was 0.88 (0.91 after logarithmic transformation), compared with the 0.82 and 0.78 of the end-of-shift MA and PGA values, respectively. A high correlation (0.86) was also found between styrene in the blood and urine. The results, obtained under field conditions with a large group of exposed workers, confirm the usefulness of the urinary excretion of styrene as an exposure index for the biological monitoring of styrene exposure.

Adolescent

Kinetics of urinary excretion and effects on colour vision after exposure to styrene.

We evaluated the influence of the body burden of styrene on biological indices of exposure and the effects of this solvent on colour perception. The exposure of 19 workers was followed during a working week by personal sampling and biological monitoring. Although no significant difference in daily exposure was observed, pre-shift values of urinary styrene and urinary mandelic acid increased significantly during the week, and the regression line between external dose and biological exposure indices changed correspondingly. These data suggest that body burden can influence the results of biological monitoring of styrene. The effect of styrene on colour vision was evaluated in two further groups: 73 exposed workers and 53 referents and 36 pairs of workers and controls. A dose-related impairment was observed, which appeared to be synergistic with age and was not significantly improved by a one-month interruption of exposure. Our data show the need to improve biological monitoring of exposure to styrene and, in particular, to establish dose-effect and dose-response relationships between exposure and early effects. Urinary excretion of styrene and colour vision assessment represent, respectively, promising indices of exposure to and an effect of styrene.

Adult

Urinary testosterone measurement by gas chromatography after solid-phase extraction and high-performance liquid chromatography.

A method was developed for the rapid determination of testosterone in urine. The procedure consists of solid-phase extraction (SPE) followed by high-performance liquid chromatographic (HPLC) clean-up before gas chromatographic determination. Recovery was evaluated by adding [3H]testosterone (10(4) cpm) to urine samples; the mean recovery of radioactivity after SPE and HPLC was 82%. Precision was estimated by repeated measurement of testosterone in four different urine samples; the coefficient of variation was 7.9% (95% confidence limits 6.1-11.4%). Accuracy was evaluated by standard addition and dilution assays; a linear relationship was found between the expected and observed values (r2 = 0.982). The method is rapid, effective and suitable for routine analysis.

Chromatography, Gas

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

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

Air Pollutants, Occupational

Serum and urinary androgens and risk of breast cancer in postmenopausal women.

Serum levels of testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone sulfate, and sex hormone-binding globulin and urinary levels of testosterone and androstanediol were compared in 75 women with breast carcinoma and 150 age-matched healthy controls. Odds ratios for quartiles of hormones, adjusted for known potential confounders, were computed using conditional logistic regression. Risk of breast cancer was positively associated with levels of all androgens in serum and urine but appeared stronger for testosterone (for trend, P = 0.03) and dehydroepiandrosterone sulfate (for trend, P = 0.06) in serum and for testosterone (for trend, P = 0.001) and androstanediol (for trend, P = 0.04) in urine. The adjusted odd ratios for high versus low quartiles were 2.7 (95% confidence interval, 1.1-6.5) for serum testosterone, 2.8 (1.1-7.4) for dehydroepiandrosterone sulfate, 4.7 (1.8-12.1) for urinary testosterone, and 3.4 (1.4-8.7) for urinary androstanediol. These observations suggest that endogenous androgenic hormones may play an important role in the epidemiology of postmenopausal breast cancer in women.

Age Factors

Accumulation of active androgens in breast cyst fluids.

80 breast cyst fluids (BCF) from 57 patients were divided by K+/Na+ ratio: 56 with ratio over 1 (type I) and 24 with ratio less than 1 (type II). Significantly higher amounts of testosterone, dihydrotestosterone and dehydroepiandrosterone sulphate (DHAS) were found in type I than in type II cysts. A positive relation was found between testosterone and dihydrotestosterone in both types. DHAS was significantly correlated with testosterone and dihydrotestosterone in type I casts only. In 52 patients, blood was sampled after cyst evacuation. Testosterone was significantly higher in blood than in BCF while dihydrotestosterone and androstenedione were significantly higher in BCF. No relation was observed between circulating levels of androgens and their intracystic concentrations. Women bearing type I cysts may be at increased risk of developing cancer. These findings support the hypothesis that androgens play a role in the hormonal aetiology of breast cancer.

Adult

Repeated serum and urinary androgen measurements in premenopausal and postmenopausal women.

Intra-individual variability for serum and urinary hormones has been inadequately considered in previous studies. Therefore, in the planning phase of a prospective study of Hormones and Diet in the Etiology of Breast Cancer (ORDET study), androgen levels have been examined at two different times in 56 women (26 in premenopause and 30 in postmenopause). Hormonal measurements in serum showed a good level of agreement for both premenopause (pre) and postmenopause (post): androstenedione pre r = 0.70 (p less than 0.0001), post r = 0.77 (p less than 0.0001); testosterone pre r = 0.73 (p less than 0.0001), post log values r = 0.74 (p less than 0.0001). Dihydrotestosterone showed a good level for premenopause only: log values pre r = 0.82 (p less than 0.0001), post r = 0.41 (p less than 0.05). Agreement levels in urine were inferior to those of serum: testosterone pre r = 0.53 (p less than 0.05), post r = 0.41 (p less than 0.05); androstanediol log values r = 0.46 (p less than 0.001), post log values r = 0.57 (p less than 0.05). Correlation between the two measurements improves considering age, parity, time of blood collection and, for urine, the interval of sample collections.

Adult

Evaluation of serum aminoterminal propeptide of type III procollagen as an early marker of the active fibrotic process in asbestos-exposed workers.

In an evaluation of the possibility of type III procollagen N-terminal propeptide (PIIINP) being an early marker of the active fibrotic process in asbestos-exposed workers, 91 asbestos workers had higher serum PIIINP concentrations than 108 referents. In 24 workers exposed to low levels of airborne asbestos, the serum PIIINP was higher than in the referents but lower than in an exposed group with higher exposure; furthermore a significant correlation (r = 0.63) was found between serum PIIINP and individual cumulative exposure. These data suggest a dose-effect relationship between asbestos exposure and PIIINP serum concentration. In addition workers with a reduced pulmonary function had higher PIIINP values than the referents or the exposed workers with normal pulmonary function. The serum PIIINP levels were related to asbestos exposure even at low airborne concentrations and may represent an early biological marker of impending fibrotic process induced by asbestos.

Adult

Acquired dyschromatopsia among styrene-exposed workers.

We investigated the occurrence of color vision loss in 75 styrene-exposed workers and in 60 referents. Color vision was evaluated by adopting the Lanthony D 15 desaturated panel, a test specifically suited to detect mild acquired dyschromatopsia. The results of the test were expressed as Color Confusion Index. Styrene exposure was evaluated with both environmental and biological monitoring. Airborne levels of the solvent were 3.2 to 549.5 mg/m3. In styrene-exposed workers color vision was significantly impaired when compared with referents matched for age. A significative correlation was found between environmental and urinary levels of styrene and Color Confusion Index excluding the influence of age in multiple regression analysis, indicating the possibility of a dose-effect relationship. The findings suggest that styrene can induce an early appearance of a dose-dependent color vision loss.

Adult

Hormones in male breast cancer.

Urinary levels of testosterone, 5 alpha-androstanediol, 17-hydroxycorticosteroids, pregnanediol, and circulating levels of testosterone, 17 beta-estradiol, dehydroepiandrosterone-sulfate, prolactin, luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin, were measured in 10 male patients with breast cancer and in a suitable group of healthy controls. No difference, either in blood or in urine, was observed between the two groups in the hormonal levels. The lack of abnormalities in peripherally detectable hormones suggests that the well recognized hormone dependency of male breast cancer may be due to some endocrine imbalance in the central (diencephalic) regulation of the sex steroids pathway. Alternatively, abnormal response of breast tissue to normal hormonal stimuli might be hypothesized in these patients.

Adult