Exposure to individual and multiple carcinogenic metals during paediatric age: an experience from an Italian urban scenario.

BACKGROUND: Exposure to single and multiple carcinogenic metals and/or semimetals represents a major environmental risk factor for public health. In particular, children are more susceptible to environmental pollutants than adults, but specific studies are still limited. The aims of the present study were: 1) to trace the exposure and co-exposure profiles to eight known or suspected carcinogenic metals and semimetals (As, Be, Cd, Co, Cr, Ni, Pb, and Sb); and: 2) to evaluate the influence of some possible interfering/confounding factors on the exposure to these elements during childhood. STUDY DESIGN: Cross-sectional study. METHODS: We recruited 159 healthy Italian children attending a primary school of the urban area of Rome, Italy. Selected metals were determined by inductively coupled plasma mass spectrometry on urinary samples collected at the end of a "typical" day (one sample for each child), while information about possible confounding/interfering factors were collected via questionnaires. RESULTS: The great part of the studied children resulted co-exposed to the monitored metals: 83.2%, 69.2%, 51.0% and 29.3% of the participants were concurrently exposed to at least two, three, four and five trace elements, respectively. Gender was the only one among the investigated variable that significantly influenced the co-exposure, with females resulting at lower risk (OR = 0.392; 95 IC = 0.156 - 0.989; p < 0.047). CONCLUSIONS: Given the importance of protecting child's health and the risks related to the exposure to carcinogenic metals, especially when they occur simultaneously, other researches in this field are strongly recommended.

Urinary biomarkers of exposure and of oxidative damage in children exposed to low airborne concentrations of benzene.

The aim of this work was to evaluate the oxidative damage to nucleic acids in children (5-11 years) associated with exposure to environmental pollutants and tobacco smoke (ETS). For each subject, urinary sampling was done twice (evening and next morning) to measure by tandem LC-MS-MS such oxidated products of nucleic acids as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and 8-oxo-7,8-dihydroguanine (8-oxoGua). Methyl tert-butyl ether (U-MTBE), benzene (U-Benz), and its metabolites (t,t-muconic and S-phenylmercapturic acids, t,t-MA and S-PMA, respectively) were determined as biomarkers of exposure to air pollution, and cotinine as a biomarker of exposure to ETS. Biomarkers of exposure (S-PMA and U-MTBE) and of DNA oxidation (8-oxodGuo) were dependent on the urbanization and industrialization levels and increased in the evening sample as compared to next morning (p<0.05). In both evening and next morning samples, 8-oxodGuo and 8-oxoGuo correlated with each other (r=0.596 and r=0.537, respectively, p<0.01) and with biomarkers of benzene exposure, particularly S-PMA (r=0.59 and r=0.45 for 8-oxodGuo and r=0.411 and r=0.383 for 8-oxoGuo, p<0.01). No such correlations were observed for U-MTBE and cotinine. Multiple linear regression analyses showed that 8-oxodGuo was positively associated with S-PMA at both sampling times (ß=0.18 and ß=0.14 for evening and next morning sampling, respectively; p<0.02) and weakly with U-MTBE (ß=0.07, p=0.020) only in the evening urines. These results suggest that the selected biomarkers of exposure to benzene, particularly S-PMA, are good tracers of exposure to complex mixtures of oxidative pollutants and that the associated oxidative damage to nucleic acids is detectable even at very low levels of exposure.

Porphyrin conjugated SiC/SiOx nanowires for X-ray-excited photodynamic therapy.

The development of innovative nanosystems opens new perspectives for multidisciplinary applications at the frontier between materials science and nanomedicine. Here we present a novel hybrid nanosystem based on cytocompatible inorganic SiC/SiOx core/shell nanowires conjugated via click-chemistry procedures with an organic photosensitizer, a tetracarboxyphenyl porphyrin derivative. We show that this nanosystem is an efficient source of singlet oxygen for cell oxidative stress when irradiated with 6 MV X-Rays at low doses (0.4-2 Gy). The in-vitro clonogenic survival assay on lung adenocarcinoma cells shows that 12 days after irradiation at a dose of 2 Gy, the cell population is reduced by about 75% with respect to control cells. These results demonstrate that our approach is very efficient to enhance radiation therapy effects for cancer treatments.

Exhaled breath analysis in suspected cases of non-small-cell lung cancer: a cross-sectional study.

Lung cancer is one of the most frequently diagnosed cancers worldwide and is still the leading cause of cancer-related deaths. There is a considerable interest in finding diagnostic methods in the disease's earliest stages. A complementary approach to imaging techniques could be provided by exhaled breath gas phase and exhaled breath condensate (EBC) analysis. The aim of this study was to quantify various biomarkers in the exhaled breath gas phase and EBC in suspected cases of non-small-cell lung cancer (NSCLC). The study involved 138 subjects with suspected lung cancer, 71 of whom had a subsequent diagnosis of NSCLC. The diagnostic power of a combination of hydrogen peroxide (H2O2)-EBC, and exhaled pentane, 2-methyl pentane, hexane, ethyl benzene, heptanal, trans-2-nonenal in distinguishing NSCLC and non-NSCLC subjects was poor-to-fair (area under the curve (AUC) = 0.68), similar to that of smoking history alone (expressed as pack-years, AUC = 0.70); a further improvement was observed when smoking history was combined with exhaled compounds (AUC = 0.80). The diagnostic power was increased in those patients with little or no past smoke exposure (AUC = 0.92) or where past smoke exposure was up to 30 pack-years (AUC = 0.85). Exhaled substances had a good accuracy in discriminating suspected cancerous cases only in those subjects with a modest smoking history (≤ 30 pack-years), but the inclusion of other exhaled biomarkers may increase the overall accuracy, regardless of tobacco smoke.

[Interpretative strategies of lung function tests: obstructive pattern]. / Strategie interpretative del deficit ostruttivo all'esame spirometrico.

INTRODUCTION: Periodic spirometric assessment is critical in the health surveillance of workers who are exposed to respiratory pollutants and plays a key role in the prevention of occupational lung diseases. OBJECTIVES: The aim of this review is to provide updates on the proper spirometry examination procedure and the criteria for data interpretation, in order to correctly diagnose obstructive impairment and longitudinal decline of pulmonary function. METHODS: A review of the most recent scientific literature was carried out focusing on those papers dealing with spirometric techniques, choice of reference values, and criteria for data interpretation. RESULTS: Over the years, the use of different diagnostic algorithms and reference values have led to poor clarity among users as well as diagnostic misclassifications. CONCLUSIONS: For spirometric data reliability it is mandatory to perform appropriate pulmonary function tests, make a correct selection of reference values and use updated interpretive criteria.

Synergistic interactions between PBDEs and PCBs in human neuroblastoma cells.

Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants. Exposure to these chemicals has been associated with developmental neurotoxicity, endocrine dysfunction, and reproductive disorders. Humans and wildlife are generally exposed to a mixture of these environmental pollutants, highlighting the need to evaluate the potential effects of combined exposures. In this study, we investigated the cytotoxic effects of the combined exposure to two PBDEs and two PCBs in a human neuronal cell line. 2,2',4,4'-Tetrabromodiphenyl ether, 2,2',4,4',5-pentabromodiphenyl ether, PCB-126 (3,3',4,4',5-pentachlorobiphenyl; a dioxin-like PCB), and PCB-153 (2,2',4,4',5,5'-hexachlorobiphenyl; a non-dioxin-like PCB) were chosen, because their concentrations are among the highest in human tissues and the environment. The results suggest that the nature of interactions is related to the PCB structure. Mixtures of PCB-153 and both PBDEs had a prevalently synergistic effect. In contrast, mixtures of each PBDE congener with PCB-126 showed additive effects at threshold concentrations, and synergistic effects at higher concentrations. These results emphasize the concept that the toxicity of xenobiotics may be affected by possible interactions, which may be of significance given the common coexposures to multiple contaminants.

[New perspectives in biomonitoring of metallic elements: the example of hexavalent chromium]. / Nuove prospettive nel monitoraggio biologico degli elementi metallici: l'esempio del cromo esavalente.

Plating industry is an important productive sector in all the national territory, because of its contribution to a high number of industrial products and crafts. In the chrome plating sector there is a specific chemical risk due to the exposure to compounds containing hexavalent Chromium [Cr(VI)]. Exhaled breath condensate (EBC) has been used to study both acute and long term exposure to Cr(VI) in chrome plating workers. Cr-EBC correlates with specific oxidative stress biomarkers. Moreover, both total Cr and its hexavalent fraction can be measured in EBC, which therefore is a promising biological fluid to assess the absorbed dose at the target organ level, the pulmonary reduction kinetics of Cr(VI) and in general its local pneumotoxic effects. EBC collection and analysis could give additional information to the traditional measures performed during biomonitoring.

Association between environmental exposure to benzene and oxidative damage to nucleic acids in children.

OBJECTIVES: To evaluate the association between environmental exposure to benzene and oxidative damage to nucleic acids in children, also considering the role of Environmental Tobacco Smoke (ETS). METHODS: 396 children living in central Italy were recruited in districts with different urbanization and air pollution. All biomarkers were determined in spot urine samples by mass spectrometric techniques to assess exposure [benzene (U-Benz), and its metabolites (t,t-muconic and S-phenylmercapturic acids, t,t-MA and S-PMA, respectively), cotinine] and nucleic acid oxidation [8-oxo-7, 8-dibydro-2'-deoxyguanosine (8-oxodGuo), 8-oxo-7, 8-dihydroguanosine (8-oxoGuo), and 8-oxo-7, 8-dihydroguanine (8-oxoGua)]. RESULTS: Biomarkers of exposure and nucleic acid oxidation increased with urbanization and were correlated with each other (r > 0.18, p < 0.005). In a multiple linear regression model, benzene exposure, assessed by S-PMA and t,t-MA, was associated (p < 0.0001) with both 8-oxodGuo (R2 = 0.392) and 8-oxoGuo (R2 = 0.193) in all areas of residence, with similar slopes. CONCLUSIONS: (i) Biomarkers of exposure to benzene increased as a function of environmental air pollution and urbanization level; (ii) U-Benz clearly distinguished both exposure to ETS and areas of residence, whereas benzene metabolites were associated only with the latter; (iii) the variance of 8-oxodGuo and 8-oxoGuo was accounted for by environmental benzene exposure, thus suggesting that benzene is a good tracer of other components of complex mixtures of pollutants causing oxidative damage to nucleic acids.

[Sleep disorders, risk of accidents and traffic accidents in a group of drivers of public transport]. / Disturbi del sonno, rischio infortunistico e incidenti stradali in un gruppo di autisti di mezzi pubblici.

In order to evaluate the prevalence of sleep disorders and visuomotor performance, a survey was conducted on 253 drivers of public transport company, aged between 25 and 64 years. Biometric data (BMI, neck circumference and waist, PA) were collected and three questionnaires were administered to investigate sleep disorders. Simple and multiple choice reaction times were administered using a computerized test battery. Records on road accidents in the period 2005-2011 and all accidents in the period 2002-2010 were analyzed. On the basis of clinical and anamnestic questionnaire, workers were divided into two groups: 194 drivers (group 1) without suspicion of sleep disorders and 59 drivers (group 2) with suspected sleep disorders, and 41 with suspected obstructive sleep apnea syndrome (OSAS). The drivers with suspicion of sleep disorders, in particular those with suspected diagnosis of OSAS, showed reaction times significantly prolonged as compared to the drivers of the group 1. In group 2, a higher incidence of (all) accidents was found, whereas the incidence of road accidents was significantly increased only in drivers with suspected OSAS. In addition to the sleep disorders, the use of drugs altering vigilance (antihistamines and benzodiazepines) were significant determinants. In-depth clinical examinations are in progress to confirm the suspected diagnosis of sleep disorders.

[Laboratory animal; allergy; asthma]. / Allergia da animali da laboratorio.

Laboratory animal allergy (LAA) may develop when susceptible persons are exposed to allergens produced by laboratory animals. LAA is associated with exposure to urine, fur, and salivae of rats, guinea pigs, dogs and rabbits. Approximately 30% of persons who are exposed to laboratory animals may develop LAA and some will also develop asthma. LAA is most likely to occur in persons with previously known allergies, especially to domestic pets. The majority of LAA sufferers experience symptoms within six months their first exposure to laboratory animals; almost all develop symptoms within three years. The most common symptoms are watery eyes and an itchy, runny nose, although skin symptoms and lower respiratory tract symptoms may also occur. Feeding and handling laboratory animals or cleaning their cages generates ten times the amount of allergens compared with undisturbed conditions. Prevention of animal allergy depends on control of allergenic material in the work environment and on organizational and individual protection measures. Pre-placement evaluation and periodic medical surveillance of workers are important pieces of the overall occupational health programme. The emphasis of these medical evaluations should be on counselling and early disease detection.

[Acute lead poisoning: a singular case of hemolytic anemia and lead colic]. / Intossicazione acuta da piombo: un caso singolare di anemia emolitica e colica saturnina.

BACKGROUND: Acute lead poisoning due to food intake is exceptional in adults and often associated with mental illness OBJECTIVES: to describe a case report of acute lead intoxication with haemolytic anemia and lead colic. METHODS: A 41-year old male patient was admitted to hospital for abdominal pain and persistent constipation. Abdominal X-ray showed a radiopaque mass in the caecum and progressive anaemia was observed The patient was discharged with a diagnosis of bowel obstruction. Due to persistence of the symptoms he was again hospitalized; abdominal X-ray showed diffuse radiopaque particles in the colon and haemoglobin (hb) had dropped to 8.7 g/dl. Blood levels of lead and zinc protoporphryin were 106.7 microg/dl and 6.6 microg/gHb, respectively. The timely start of chelating therapy led to a rapid return to normal peripheral blood counts and a decline in blood lead levels. RESULTS: Although acute lead poisoning due to intake with food is exceptional in adults and often associated with mental illness, in this case, it was not possible to clarify the route and vehicle of ingestion of the toxic. Lead body burden was shown as a caecal mass, probably as a result of ingesting a single bolus of lead dust which, considering the size and density of the mass, was estimated as weighing several grammes. This acute lead intake induced an acute haemolysis due to enhanced fragility of the erythrocyte membrane. CONCLUSIONS: In the course of acute lead intoxication, the critical organ is not the bone marrow, but rather the red blood cell, leading to haemolysis and anaemia.

[Environmental and biological monitoring of exposure to monoaromatic hydrocarbons and to methyl tert-butyl ether in a group of petrol station workers]. / Monitoraggio ambientale e biologico dell'esposizione ad idrocarburi mono-aromatici ed a metil tert-butil etere in un gruppo di lavoratori addetti all'erogazione di carburanti.

The aim of the study was to evaluate biomarkers of exposure to gasoline in petrol station workers by a combined approach of environmental and biological monitoring. The personal exposure to benzene, toluene, ethylbenzene and xylene (BTEX) and the urinary levels of BTEX, methyl tert-butyl ether (U-MTBE), trans,trans-muconic (t,t-MA) and S-phenylmercapturic acids (S-PMA) and cotinine were determined by mass spectrometry coupled chromatographic techniques. U-MTBE levels were strictly influenced by occupational exposure to gasoline, whereas both U-B and S-PMA levels depended from smoking habits and occupational exposure.

[Biological monitoring and exposure to silica: application of new dose and effect biomarkers]. / Monitoraggio biologico ed esposizione a silice: applicazione di nuovi indicatori di dose e di effetto.

Si-CAE was measured in 16 composite marble industry workers furthermore, a spirometry was performed and 8oxoGua, 8oxoGuo 8oxodGuo, SP-A, SP-D, CC16 and HO-1 were dosed. A lower spirometric values (FEV1 and FVC) were observed among workers compared with controls and the following markers were increased: Si-CAE, 8oxoGuo and HO-1 expression. This study shows that exposure to silica can increase the levels of Si-CAE, which can be used to estimate the dose to the target. Finally, nonspecific spirometric abnormalities and an increase in biomarkers of effect were observed.

[Early molecular diagnosis of lung cancer: a method to rule out the disease]. / Diagnosi molecolare precoce del tumore polmonare: un metodo per escludere la malattia.

Aim of this study was the determination of new markers for the diagnosis of lung cancer. 61 patients with non-small cell lung cancer (NSCLC) and 42 controls were enrolled. In the NSCLC patients the following markers were increased: H2O2 in exhaled breath condensate, pentane, hexane, nonenal, trans-2-heptanal, trans-2-nonenal in exhaled breath, while pentanal was decreased. Using multivariate statistical models, a sensitivity of 73.8% and a specificity of 76.8% were calculated. This study shows that with this non-invasive test followed by a most powerful test on positives (e.g. PET) it is possible to decrease the number of false positives.

Assessing variability and comparing short-term biomarkers of styrene exposure using a repeated measurements approach.

The aim of this work is to compare several short-term biomarkers of styrene exposure, namely urinary styrene (StyU), mercapturic acids (M1+M2), mandelic acid (MA), phenylglyoxylic acid (PGA), phenylglycine (PHG), and 4-vinylphenol conjugates (VP), for use as biomarkers of exposure in epidemiologic studies. A repeated measurements protocol (typically 4 measurements per worker over 6 weeks) was applied to measure airborne styrene (StyA) and urinary biomarkers in 10 varnish and 8 fiberglass reinforced plastic workers. Estimated geometric mean personal exposures to StyA were 2.96mg/m(3) in varnish workers and 15.7mg/m(3) in plastic workers. The corresponding levels of StyU, M1+M2, MA, PGA, MA+PGA, PHG and VP were 5.13microg/L, 0.111, 38.2, 22.7, 62.6, 0.978, and 3.97mg/g creatinine in varnish workers and 8.38microg/L, 0.303, 146, 83.4, 232, 2.85 and 3.97mg/g creatinine in plastic workers. Within-worker (sigma(wY)(2)) and between-worker (sigma(bY)(2)) variance components were estimated from the log-transformed data as were the corresponding fold ranges containing 95% of the respective lognormal distributions of daily levels ((w)R(0.95)) and subject-specific mean levels ((b)R(0.95)). Estimates of (w)R(0.95) (range: 4-26) were generally smaller than those of (b)R(0.95) (range: 5-790) for both environmental and biological markers; this indicates that exposures varied much more between workers than within workers in these groups. Since attenuation bias in an estimated exposure-response relationship increases with the variance ratio lambda=sigma(wY)(2)/sigma(bY)(2), we estimated values of lambda for all exposure measures in our study. Values of lambda were typically much less than one (median=0.220) and ranged from 0.089 for M1+M2 in plastic workers to 1.38 for PHG in varnish workers. Since values of lambda were 0.147 and 0.271 for StyA in varnish workers and plastic workers, respectively, compared to 0.178 and 0.210 for MA in the same groups, our results suggest that either air measurements or conventional biomarker measurements (urinary MA) would be comparable surrogates for individual exposures in epidemiologic studies.

Occupational asphyxiation by unknown compound(s): environmental and toxicological approach.

During a routine truck-tank washing operation, five healthy workers were found motionless inside an empty tanker. Four of them died inside the tanker while the fifth died the following day in hospital. Since the true nature of the fatal compound(s) were not known, a rigorous environmental and toxicological approach supported by autopsy findings was essential to clarify the cause of death. Environmental results indicated that H(2)S fumes arising from the liquid sulfur previously shipped were responsible for the serial deaths, also confirmed by a simulation performed on two similar truck-tanks. These environmental findings were supported by toxicological analyses through the measurement of thiosulfate, one of the main H(2)S metabolites. Abnormal thiosulfate concentrations from 1.1 to 186.2 mg/kg were revealed in all post-mortem biological samples (blood, lung, liver, kidney, brain and fat). Finally, the cluster analysis performed on thiosulfate body distribution contributed to establishing the time of death according to the accident scene reconstruction. This report presents valuable findings in correctly identifying the cause of death in gas asphyxiation cases by unknown compound(s).

An integrated approach to biomonitoring exposure to styrene and styrene-(7,8)-oxide using a repeated measurements sampling design.

The aim of this work was to investigate urinary analytes and haemoglobin and albumin adducts as biomarkers of exposure to airborne styrene (Sty) and styrene-(7,8)-oxide (StyOX) and to evaluate the influence of smoking habit and genetic polymorphism of metabolic enzymes GSTM1 and GSTT1 on these biomarkers. We obtained three or four air and urine samples from each exposed worker (eight reinforced plastics workers and 13 varnish workers), one air and urine samples from 22 control workers (automobile mechanics) and one blood sample from all subjects. Median levels of exposure to Sty and StyOX, respectively, were 18.2 mg m(-3) and 133 microg m(-3) for reinforced plastics workers, 3.4 mg m(-3) and 12 microg m(-3) for varnish workers, and <0.3 mg m(-3) and <5 microg m(-3) for controls. Urinary levels of styrene, mandelic acid, phenylglyoxylic acid, phenylglycine (PHG), 4-vinylphenol (VP) and mercapturic acids (M1+M2), as well as cysteinyl adducts of serum albumin (but not those of haemoglobin) were significantly associated with exposure status (controls

Opinion of hepatic transplant waiting list patients regarding split liver transplantation.

BACKGROUND: Split liver transplantation (SLT) increases organ supply for hepatic transplantation. Long-term patient survival and complication rates seem to be equivalent between orthotopic liver transplantation (OLT) and SLT. There are controversies among transplant physicians due to an ethical dilemma between benefiting individual needs or those of society. Barshes and Goss (Am J Transplant 5:2047, 2005) demonstrated that the majority of adult liver transplant candidates are favorable to SLT. The aim of our study was to evaluate the opinions of patients at a Brazilian university hospital regarding SLT. MATERIALS AND METHODS: A questionnaire with 14 questions was applied to 50 patients included in a hepatic transplant waiting list regarding SLT. RESULTS: The overall attitudes of 66% of the participants were classified as utilitarian, 31% were classified as self-preserving, and 3% were undecided. Ninety-one percent of patients would be willing to share even if their expected survival after SLT was shorter than that with OLT. For 77% of patients, children must have priority over adults. However, 83% were unaware of the donors for pediatric transplantations. CONCLUSIONS: SLT is a consistent solution for organ demand despite controversies among transplant physicians. The present study demonstrated that most patients were favorable to SLT. In conclusion, attitudes toward graft sharing are not barriers to SLT.

[Non-invasive assessment of lung pathobiology in hairdressers]. / Valutazione non invasiva della patobiologia polmonare in una coorte di lavoratori del settore acconciatura.

BACKGROUND: Hairdressers are exposed to chemical agents with potentially irritant and sensitizing effects on airways. OBJECTIVES: To asses the presence of respiratory symptoms and biochemical and functional changes of the airways in a cohort of hairdressers. METHODS: Respiratory symptoms, lung function tests, fractional exhaled nitric oxide (FE(NO)50) and selected oxidative stress biomarkers [hydrogen peroxide (H2O2), malondialdehyde (MDA) and 4-hydroxynonenal (HNE)] in exhaled breath condensate (EBC) were assessed in 23 hairdressers on a rest day (Group 1); 12 workers (Group 2) were willing to perform the same tests at the beginning (BS) and at the end of a shift (ES) on the same working day. Eighteen subjects not occupationally exposed to airways irritants formed the control group. RESULTS: Most of the hairdressers reported respiratory symptoms during work; however, all (except one) showed normal spirometry indexes. FE(NO)50 levels were within the reference limits and did not change comparing BS vs. ES sampling. H2O2 and HNE values in EBC were higher in Group 1 (H2O2: 0,16 [0,05-0,19] microM; HNE: 0,94 [0,82-1,22] nM) than in controls (H2O2: 0,05 [0,02-0,09] microM; HNE: 0,61 [0,49-0,78] nM, p < 0,001). In Group 2, H2O2 and MDA levels were higher in EBC collected at ES (0,56 [0,23-3,62] mM and 5,21 [4,93-5,95] nM) in comparison with the BS values (0,11 [0,03-0,28] mM and 4,12 [3,46-5,16] nM, p < 0,001 and p < 0,02, respectively). CONCLUSIONS: Increased levels of oxidative stress biomarkers are detectable in EBC of hairdressers, without impairment in respiratory function. Exhaled biomarkers of oxidative stress may be sensitive end points for evaluating early biochemical changes in the airways of hairdressers.