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.

Role of interleukin-23 circulating levels increase in resected colorectal cancer before and after chemotherapy: preliminary data and future perspectives.

Expression of IL-23, a heterodimeric cytokine involved in the induction of Th17 cells, is increased in human tumors. Although the endogenous IL-23 expression has been reported to promote tumor development and growth, the studies using local and systemic administration of IL-23 have shown that its application at the excessive amount induces antitumor immune responses. IL-23 is, today, considered the key driver of intestinal inflammation and its role in inflammatory responses is tissue-specific. The aim of this study was to investigate the role of circulating levels of IL-23 in patients with resected colorectal cancer (CRC) before and after chemotherapy, respect to healthy controls. Twenty-five patients were enrolled between June 2007 and January 2009, and followed through 2010. All patients underwent chemotherapy, mostly FOLFOX4. Twenty-sex and age-matched healthy donors were recruited as controls. IL-23 serum concentrations, measured by a quantitative enzyme immunoassay technique, were significantly higher in patients with resected CRC (26.02 ± 28.63 pg/ml versus 7.1 ± 6.4 pg/ml, P < 0.001) and after chemotherapy respect to controls (21.74 ± 23.82 pg/ml versus 7.17 ± 6.43 pg/ml, P < 0.001). An increase was documented also before chemotherapy (26.02 ± 28.63 pg/ml versus 21.74 ± 23.82 pg/ml, P = 0.7) but not statistically significant. This work investigated, for the first time, the role of IL-23 in CRC resection and chemotherapy, showing no correlation with the severity of disease, tumor removal, and chemotherapeutic treatment. However, other works are needed to better clarify if IL-23 could be considered a key-molecule in human CRC and a target for tumor treatment.

[Genetic markers of individual susceptibility and oxidative stress in subjects exposed to low dose of benzene. Preliminary data]. / Indicatori genetici di suscettibilità individuale e stress ossidativo in soggetti esposti a basse dosi di benzene. Dati preliminari.

In the present study we used AOPPs and AGE as early markers of oxidative stress in refinery oil workers. In addition we evaluated whether a genetically determined reduction in the ability to detoxify electrophilic compounds, such as that expected among individuals with glutathione S-transferase (GST) null genotypes might influence the levels of AOPPs thus increasing toxicity. The study was performed on 25 oil refinery workers and in 18 age-matched control subjects. We found a statistically significant increase of AOPPs in exposed workers with respect to controls while AGE levels were not different. Finally serum level of AOPPs and AGE were not correlated with the different GTS genotypes.

[New data on pumice's structure and biological effects among miners and millers]. / Nuove acquisizioni sull struttura dell pietra pmie e possibili effetti pleurici nei lavoratori del settore.

Pleural plaques among pumice workers on Lipari Island have been described and the Authors have suggested the hypothesis that such biological effect could be related to the particles' morphology characterized by the presence of elements similar to fibers. Analysis on compact bulk materials and on dust samples from different sites of the Island have been performed to obtain information on the chemical composition of such materials. The Scan Electron Microscopy (SEM) analyses confirm the presence of fibrous particles with a chemical structure similar to the Refractory Ceramic Fibers (RCF) composition. These results could explain the presence of plural plaques among the workers and new clinical and epidemiological evaluations of the potential effects associated to this exposure are needed.

Serum levels of carbonylated and nitrosylated proteins in mobbing victims with workplace adjustment disorders.

AIM: Today the most important problem in the work place is psychological abuse, which may affect the health because of high levels of stress and anxiety. There is evidence that most psychiatric disorders are associated with increased oxidative stress but nothing is reported about the presence of oxidative stress in mobbing victims. METHODS: This study has been carried out in a group of 19 patients affected by workplace mobbing-due adjustment disorders, in comparison with 38 healthy subjects, to evaluate whether oxidative stress may be induced by mobbing. RESULTS: Serum levels of protein carbonyl groups and of nitrosylated proteins, biological markers of oxidative stress conditions, were higher than those measured in healthy subjects. CONCLUSIONS: These findings may contribute to a better understanding of the redox homeostasis dysregulation occurring in victims of workplace mobbing.

[Genetic polymorphisms (GSTT1 e GSTM1) and urinary excretion of t,t-muconic acid among refinery workers]. / Polimorfismi genetici (GSTT1 e GSTM1) ed escrezione urinaria di acido t,t-muconico in lavoratori di una raffineria.

Many xenobiotics agents are metabolized by enzymes mechanisms through Phase I, activating substances procancerogene through oxidative reactions, and / or through mechanisms Phase II, acting on metabolic intermediate products of oxidative processes with conjugation reactions with endogenous mediators, in order to generate hydrophilic products that can be easily excreted by the body. Among the enzymes Phase II is a heterogeneous group represented by glutathione S-transferase. Genetic polymorphisms encoding for these enzymes (GSTs) are responsible phenotypic expression of enzymes specifically involved in the detoxification and elimination of different genotoxic agents (IPA, toluene, benzene). Accordingly, the authors have investigated a population of subjects professionally exposed to benzene (used in active refining and storage of crude oil) in order to assess the genetic profile in relation to possible null genotype (responsible for the failure phenotypic expression of protein) of polymorphism GSTT1 and GSTM1 and correlate the impact that the genotype effect of normal metabolic pathway t, t-muconico.

[Efficacy of preventive measures for reducing professional disorders due to pumice powder]. / Efficacia degli interventi di prevenzione nella riduzione delle malattie professionali da polvere di pomice.

The analysis of the incidence of pumice pneumoconiosis in the period 1970-2002 allows to evaluate the positive effects, particularly on the deadly forms of the disease, of the technical interventions aimed at reducing dusts. The main interventions in the field of the workmanship of pumice were made at the beginning of 70s, with the introduction of electrofilters in the working cycle and the change of the pumice desiccation system, from plate ovens to closed-cycle rotating ovens. This eliminated the need for manual shedding of pumice stones on oven plates. That duty had caused, between 70s and 80s, an high incidence of deadly forms of pneumoconiosis, which dramatically decreased with the reduction of workers exposed to the above risk. A comparison between the period 1970-75 (before preventive technical interventions) and the period 1976-2002 clearly shows an evident decrease both of deadly forms of pneumoconiosis and of acceptance of appeals for professional silicosis.

[Screen dermatitis and visual display units]. / Screen dermatitis e videoterminali.

Over the last fifteen years, the increasing prevalence of screens and electromagnetic devices used in a number of activities has determined the occurrence of new emerging clinical problems. Hence the need to evaluate the ergonomic aspects of the professions using such equipment to study the effects of electromagnetic fields on human health. The objective difficulties to standardize the studies on this field makes controversial the debate on the evidences in support of these nosographical entities and on the possible causative factors. One interesting area is that of dermatological diseases. The authors present the results of a study on the incidence of dermatological diseases of the face and of the neck in a population of screen workers. To achieve this goal subjects underwent dermatological counselling during the periodic of monitoring visits. Subjects were then identified in two groups: screen workers and as a control group, subjects not exposed to electronic equipments. Members of the first group when compared with those of the second, suffered more frequently from skin diseases, although there was just a statistical trend. However skin diseases were distributed with different frequency in the two groups and seborrheic dermatitis was much more represented among screen workers.

Computed tomography features of liparitosis: a pneumoconiosis due to amorphous silica.

The purpose of this study was to describe the radiological features of pleural, parenchymal and mediastinal damage due to occupational inhalation of pumice. In total, 31 workers were evaluated for annual follow-up. Spiral computed tomography (CT) was obtained in the three patients with evident parenchymal abnormalities at chest radiograph. High-resolution computed tomography (HRCT) was performed in the remaining 28 subjects with no radiographical evidence of pleuropulmonary damage or evidence of pleural plaques, in order to exclude parenchymal involvement. Pumice samples were analysed by radiograph diffraction and scanning electron microscopy. Spiral CT showed parahilar conglomerate masses containing fine reticular calcifications in three of 31 (9.7%) patients. HRCT showed several bilateral pleural plaques, without any parenchymal lesion in eight of 28 (28.6%) cases. Statistical analysis indicated correlation between CT findings and pulmonary function, as well as exposure to pumice. The analysis of pumice excluded the presence of asbestos. The findings from this study suggest that pleural plaque may be the only sign of disease in patients with a history of pumice inhalation. However, conglomerate parahilar masses are probably due to exposure to massive amounts of heated pumice, and seem to have different pathogenesis and histopathological characteristics to silicosis.

Early events of experimental exposure to amorphous and crystalline silica in the rat: time course of surfactant protein D.

Pneumoconioses determined by chronic inhalation of different kinds of silica present with peculiar clinical and histopathological features. Silicosis, caused by crystalline silica, is characterized by typical fibrous parenchymal nodules. Less defined are pneumoconioses due to amorphous silica. Aim of current experimental research on silicosis is to investigate the early events that lead to nodular fibrosis of the lung. A secretory component of the pulmonary environment, surfactant, seems to be involved in silica toxicity; surfactant protein D is a protein constituent, apparently involved in the homeostasis of the phospholipid component. We studied the behaviour of SP-D 2, 12 and 24 hours after treatment with 200 mg/kg crystalline silica or pumice powder suspended in 400 microl/kg saline solution and instiled intratracheally to rats. Both immunohistochemical localization and immunoblotting quantification demonstrated a sensible increase in intracellular SP-D, localized in alveolar type II cells and some bronchiolar epithelial cells, 2 hours after treatment. Increment appears less marked 12 hours after administration, reaching again levels comparable to control at 24 hours. The behaviour of SP-D after pumice instilation is similar, but with a significantly minor increment at 2 hours. These results indicate crystalline silica as responsible for a stronger acute injury of pulmonary tissue.

[Cutaneous histopathologic changes in laboratories working in the processing of petroleum]. / Modificazioni isotopatologiche cutanee in lavoratori addetti alla movimentazione di prodotti petroliferi.

Petroleum and its derivatives are a complex mixture of many constituents in varying proportions, such as polycyclic aromatic hydrocarbons, alcohols, ethers and additives. It is well established that petroleum derivatives are absorbed through the skin but exposure has not been quantified. Manifestations of cutaneous exposure vary from squamous cell carcinoma to irritative contact dermatitis such as occurs in the workplace. The aim of the investigation was to evaluate cutaneous histomorphological alterations in a group of 10 healthy workers occupationally exposed to repeated and low amounts of gasoline for a prolonged period. Histological examination and immunocytochemical techniques were performed after taking punch biopsies. The results showed the presence of perivascular lympho-plasma cell infiltration and leucocyte cells scattered in the dermal layer. A mild increase in epidermal Langerhans cells was also observed while the detection of the Ki-67 antigen in keratinocytes gave a normal appearance. In conclusion, the overall histomorphological and immunological features was not specific, but resembled skin reactions due to several irritative agents. Such skin alterations can lead to contact dermatitis.

Ocular discomfort and conjunctival alterations in operating room workers. A single-institution pilot study.

OBJECTIVES: The aim of this pilot study was to relate the eye symptoms complained of by subjects working in the operating rooms of a hospital in southern Italy, with the observations of alterations of the ocular surface. METHODS: An epidemiological study was carried out by a questionnaire aimed at investigating the prevalence of ocular discomfort symptoms among 213 subjects working in operating rooms and 40 subjects working in the wards. The investigated symptoms were the following: tiredness, heaviness, burning, redness, tearing, itching, blinking, foreign body sensation, and photophobia. A randomised comparative study of the ocular surface and conjunctival cytology was also carried out, comparing two groups of age- and gender-matched subjects. Group 1 included 24 subjects randomly chosen from the operating room workers with ocular discomfort symptoms; group 2 included ten subjects randomly enrolled from hospital personnel working in the wards. Ophthalmological examination of the ocular surface was performed on each subject in the following order: slit-lamp examination, break-up time (BUT) of the pre-corneal tear film, corneal fluorescein stain, lachrymal basal secretion test, conjunctival impression cytology. RESULTS: A high prevalence (72.3%) of ocular discomfort symptoms was reported by operating room workers, while in ward personnel the prevalence was 55% (P = 0.04). The ocular tests showed that the conjunctival features and BUT were statistically significantly altered in subjects in group 1. Also, the conjunctival impression cytology study showed statistically significant alterations of all the investigated parameters: specimen cellularity, cell-to-cell contacts, nucleus/cytoplasm ratio, chromatin pattern, goblet cell distribution, keratinisation and the total cytological score. CONCLUSIONS: Our results show that self-reported eye complaints and ocular surface alterations have a high prevalence in subjects working in the operating rooms. This seems to indicate that the operating room environment could play a role in the onset of the eye disturbances.

[Occupational activity with risk of leptospirosis. Prevention and health surveillance]. / Rassegna delle attività lavorative a rischio d'infezione da leptospire. Prevenzione e sorveglianza sanitaria.

The analysis of the epidemiological studies carried out in Italy give us the idea for a very precise survey of the occupational leptospirosis. We have identified the occupational hazards and the precautionary measures. In Italy the first epidemiological data about human leptospirosis goes back to 1917. During following decades were highlighted several occupational forms of leptospirosis, specifically seasonal epidemics among rice-workers. Epidemiological studies carried out in Italy from 1950 to 1990 showed that leptospirosis was again widespread although precautionary measures and there was a probable spread of the "minor leptospirosis" at the same time of common cases of "major leptospirosis". The latest data issued by Ministry of the Health related years '94-'97 confirm the persistence of leptospirosis, for the most part in the north. However there is a problem of underestimate because many times human leptospirosis show itself with minor clinical forms. In the working environment is essential the function of the Medico Competente. He must avail himself of the precautionary measures for the biological risk specified in D.lgs 626/94.

Myeloproliferative Disease: Markers of Endothelial and Platelet Status in Patients with Essential Thrombocythemia and Polycythemia Vera.

Vascular complications are the main cause of morbidity in polycythemia vera (PV) and essential thrombocythemia (ET). To investigate plasma concentrations of soluble P-selectin (sP-Sel.), soluble E-selectin (sE-Sel.) and soluble thrombomodulin (sTM) in relation to the presence of thromboembolic events 38 patients with Chronic Myeloproliferative Disorders (CMD) (14 PV pts and 24 ET pts), 15 age - matched controls and 15 patients with secondary thrombocytosis were studied. Plasma levels of P-Sel., E-Sel. and TM were significantly increased in the group of patients as compared with control subjects (respectively p < 0.001, p < 0.04 and p < 0.01). sP-Sel. levels showed no significant difference between the patients and those with secondary thrombocytosis. No difference in sP-sel levels were also observed between subgroups of CMD patients with and without vascular complications. However, among patients with ET, those with thrombosis had higher sP-Sel levels than those without thrombosis (1.177 +/- 110.48 ng/ml vs 816.25 +/- 99.27 ng/ml). High levels of sE-Sel and sTM were found in CMD patients (71.93 +/- 39.08 ng/ml and 35.81 +/- 20.79 ng/ml, respectively). Plasma sE-Sel. concentration was significantly higher in CMD patients with thrombosis than that in CMD patients without thrombosis (p < 0.001). There was no difference in sTM concentration between two groups. These findings indicate that sustained endothelium and platelet activation is present in patients with ET and PV and it might contribute to the pathogenesis of thromboembolic events in these patients.

A cross-sectional study of workers with occupational exposure to petroleum derivatives.

Expression of human involucrin (hINV) a protein of the cornified cell envelope, was studied in the skin of gasoline storage workers, in order to evaluate the effects of the exposure to petroleum derivatives. A total of 25 forearm skin punch biopsies were carried out. Twenty of which were performed on exposed subjects and five on controls. The specimens were processed for immunohistochemistry and hINV expression was evaluated using an anti-hINV monoclonal antibody and the ABC technique. Percentage of immunolabeled keratinocytes was significantly higher in subjects exposed to gasoline with respect to the control sample. A premature hINV expression was detected both in suprapapillary and interpapillary keratinocytes. Such overexpression of hINV seems to be related to an attempt of increasing skin defence mechanism. Therefore it was concluded that also in absence of clinical skin manifestation the exposure to gasoline determines an involvement of keratinocytes on molecular basis.

Effect of inhaled glutathione on airway response to 'Fog' challenge in asthmatic patients.

OBJECTIVE: We report on the effect of glutathione, an antioxidant compound on the airway response to the ultrasonically nebulised distilled water (UNDW, 'fog') challenge. METHODS: 12 subjects with mild-to-moderate bronchial asthma underwent double-blind, cross-over pretreatment, administered 30 min earlier, in a randomised order with inhaled glutathione (G) (600 mg), sodium cromoglycate (SCG) (20 mg) and placebo (P), followed by the challenge. RESULTS: After P pretreatment UNDW challenge caused a mean 20.41% decrease in FEV-1 (p < 0.05), after G, a mean 6.04% fall in FEV-1 (p = n.s.), and after SCG a mean 5.99% fall in FEV-1 (p = n.s.). CONCLUSIONS: G significantly attenuated 'fog'-induced falls in FEV-1 (p < 0.001 compared with P) and showed a protective effect on UNDW-induced bronchoconstriction.

Markers of Endothelial and Platelet Status in Patients with Essential Thrombocythemia and Polycythemia Vera.

Vascular complications are the main cause of morbidity in polycythemia vera (PV) and essential thrombocythemia (ET). To investigate plasma concentrations of soluble P-selectin (sP-Sel.), soluble E-selectin (sE-Sel.) and soluble thrombomodulin (sTM) in relation to the presence of thromboembolic events 38 patients with Chronic Myeloproliferative Disorders (CMD) (14 PV pts and 24 ET pts), 15 age-matched controls and 15 patients with secondary thrombocytosis were studied. Plasma levels of P-Sel., E-Sel. and TM were significantly increased in the group of patients as compared with control subjects (respectively p < 0.001, p < 0.04 and p < 0.01). sP-Sel. levels showed no significant difference between the patients and those with secondary thrombocytosis. No difference in sP-sel levels were also observed between subgroups of CMD patients with and without vascular complications. However, among patients with ET, those with thrombosis had higher sP-Sel levels than those without thrombosis (1.177 ± 110.48 ng/ml vs 816.25 ± 99.27 ng/ml). High levels of sE-Sel and sTM were found in CMD patients (71.93 ± 39.08 ng/ml and 35.81 ± 20.79 ng/ml, respectively). Plasma sE-Sel. concentration was significantly higher in CMD patients with thrombosis than that in CMD patients without thrombosis (p < 0.001). There was no difference in sTM concentration between two groups. These findings indicate that sustained endothelium and platelet activation is present in patients with ET and PV and it might contribute to the pathogenesis of thromboembolic events in these patients.

Increased concentration of circulating acid glycosaminoglycans in chronic lymphocytic leukaemia and essential thrombocythaemia.

To verify whether the increase in the number of circulating blood cells that synthesize glycosaminoglycans, B-lymphocytes or platelets, in proliferative disorders, may be associated with changes in the circulation of acid glycosaminoglycans, the serum and plasma concentrations of these polysaccharides have been measured in terms of their sugar components, following isolation and purification by chromatographic methods, in patients with chronic lymphocytic leukaemia or with essential thrombocythaemia and in healthy controls. In the patients, the concentrations of total circulating glycosaminoglycans and of both glucosamine-containing and galactosamine-containing serum glycosaminoglycans were significantly higher than in controls. These concentrations did not significantly correlate with the number of lymphocytes in patients with chronic lymphocytic leukaemia and of platelets in patients with essential thrombocythaemia. Analytical data suggest that excess glycosaminoglycans are mainly composed of chondroitin sulphate molecules and contain heparan sulphate structures.