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.

[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.

Ligasure Precise vs. conventional diathermy for Milligan-Morgan hemorrhoidectomy: a prospective, randomized, multicenter trial.

PURPOSE: Milligan-Morgan hemorrhoidectomy using radiofrequency dissection (Ligasure) has been proposed instead of conventional diathermy in view of its potential benefits in terms of postoperative anal pain and better hemostatic control, but the medical literature is still controversial. This multicenter, randomized, controlled trial was designed to compare the outcomes between Ligasure and conventional diathermy hemorrhoidectomy in the Milligan-Morgan procedures in a sufficient number of patients. METHODS: Patients with Grades III and IV hemorrhoids were randomized to two groups: Ligasure hemorrhoidectomy and conventional diathermy. Postoperative anal pain was measured by the Visual Analog Scale (VAS) and the analgesia required. Postoperative complications, wound healing, and return to working activities also were evaluated as secondary outcomes. RESULTS: A total of 273 patients, well matched for age, gender, working activity and grade of hemorrhoids, were randomized to two groups: Ligasure 146, and diathermy 127. The severity of postoperative anal pain was significantly less in the Ligasure group when measured at least 12 hours after defecation (P < 0.01), whereas it was similar at the time of defecation. The Ligasure group had significantly lower requirements for painkiller pills. There were no significant differences in early and late complications. Return to work and normal activities was significantly faster in the Ligasure group. CONCLUSION: Ligasure hemorrhoidectomy is an effective procedure for Grades III and IV hemorrhoids and facilitates a faster return to work and normal activities by reducing postoperative pain.

Biomass burning and carbon monoxide patterns in Brazil during the extreme drought years of 2005, 2010, and 2015.

In the 21st century, severe droughts associated with climate change will increase biomass burning (BB) in Brazil caused by the human activities. Recent droughts, especially in 2005, 2010, and 2015, caused strong socioeconomic and environmental impacts. The 2015 drought considered the most severe since 1901, surpassed the 2005 and 2010 events in respect to area and duration. Herein, based on satellite data, the 2005, 2010 and 2015 drought impacts on wildfire episodes and carbon monoxide (CO) variability during the dry and the dry-to-wet transition seasons were examined. The BB occurrences in the dry season were fewer during 2015 than during 2005 (-44%) and 2010 (-47%). Contrasting, the BB events in the dry-to-wet transition season, were higher during 2015 than during 2005 (+192%) and 2010 (+332%). The BB outbreaks were concentrated in the southern and southwestern Amazon during 2005, in the Cerrado region during 2010, and mainly in the central and northern Amazon during 2015, an area normally with few fires. The CO concentration showed positive variations (up to +30%) occurred in the southern Amazon and central Brazil during the 2005 and 2010 dry seasons, and north of 20 °S during the 2015-2016 dry-to-wet transition season. The BB outbreaks and the CO emissions showed a considerable spatiotemporal variability among the droughts of 2005, 2010, and 2016, first of them driven by local conditions in the tropical North Atlantic (TNA), characterized by warm than normal sea surface waters and the other two by the El Niño occurrences.

Embolism to the brain during carotid stenting and surgery.

UNLABELLED: The aim of this study was to assess the prevalence and clinical relevance of microembolism in one hundred unselected patients submitted to 50 carotid endarterectomy (CEA) and 50 carotid stenting (CAS) procedures from January 2005 to January 2006 for hemodynamic lesions of the carotid bifurcation (> 70% stenosis). MATERIAL AND METHODS: High-resolution Colour-Flow Mapping (CFM), Transcranial Doppler (TCD), cerebral computed tomography (CT) or magnetic resonance (MR) and four psychometric tests (Mini mental state, Beck depression inventory, Zung anxiety inventory, SF-12) were carried out in the preoperative evaluation in all the patients. In the CEAs loco-regional anesthesia (100%), patch angioplasty (84%) and Pruitt- Inahara shunt (4%) were employed; in the CASs local anesthesia (100%), three different carotid stents (Precise-Cordis, Acculink-Guidant and Carotid Wallstent-Boston Scientific) and three temporary distal filter protection devices (Angioguard-Cordis, Accunet-Guidant, Filterwire-EZ- Boston Scientific), without pre-dilatation, were employed. TCD monitoring was used intra-operatively and 12 hours post-operatively to evaluate the presence and the number of microembolic events (ME's) and to investigate the efficiency of neuroprotective filter devices. The efficacy of the in situ opened filter was judged evaluating the decrease of mean blood velocity in ipsilateral middle cerebral artery and the reduction rate of microembolic events (number of microemboli detected during the entire procedure/number of microemboli detected during the filter positioning). Diffusion-weighted magnetic resonance imaging (DWI) of the brain was obtained within 24 to 48 hours after the procedures to detect new ischemic brain lesions. Psychometric tests were repeated at the discharge of the patient and after two months to evaluate cognitive faculties. RESULTS: During postoperative period (30 days) and follow-up, no procedure-related death and three regressive minor strokes occurred : 1 in CEA (2%) and 2 in CASs (4%) ; a cranial nerve lesion occurred in CEA (2%). TCD monitoring showed ME's (a mean of five events) in 37 CEAs (74%) and in 50 CASs (100%) (a mean of 60 ME's). In five patients submitted to CAS repeated microemboli occurred during one hour postoperative TCD control (10%). A 10-30% decrease of mean blood velocity basal value was recorded in the ipsilateral middle cerebral artery when the filter device was opened. A mean 70% reduction of ME's was obtained with a cerebral protection system deployed. Postoperative DWI detected new focal ischemic lesions in 24 patients [22 after CAS (44%) (a mean of 5 new ipsi and contra-lateral lesions) , and 2 after CEA (4%). Cognitive capability worsened in 20 patients [18 after CAS (36%) e 2 after CEA (4%)]. CONCLUSIONS: Mortality and morbidity rates of patients submitted to CAS are comparable to the results obtained by CEA. A great number of ME's are recorded by TCD during endovascular procedures, more than during open surgery. ME's due to CAS are reduced by filter protection devices, but the cognitive faculties in a great number of "asymptomatic" patients are decreased after CAS.

[Chronobiological evaluation of effects biomarkers and sampling]. / Importanza della valutazione cronobiologica degli indicatori di effetto per una corretta strategia di campionamento.

Occupational exposure to oxidants is often associated with an increase in the levels of oxidative DNA damage in urine. Besides 8-hydroxy-2'-deoxyguanosine (8-oxo-dG), other products of position-8 guanine oxidation have been identified in urine, including 8-hydroxy-guanine (8-oxo-G) and 8-hydroxyguanosine (8-oxy-Guo). The aim of the present study was the characterization of these effect biomarkers in terms of inter- and intra-individuals varaibility, as well as in terms of their excretion profile during a 24 h-period. Urine samples were collected from 11 volunteers (6 samples/day). Urine concentrations of 8-oxo-G, 8-oxo-Guo, and 8-oxo-dG were determined by liquid chromatography-tandem mass spectrometry. The inter-individual variability, expressed as variation coefficient, was 85-150% for 8-oxo-G, 20-45% for 8-oxo-Guo, and 30-45% for 8-oxo-dG. The statistical anaysis for repeated measurements showed that none of the biomarkers was affected by significant variation during the day (one-way ANOVA, p < 0.05), thus excluding the existence of a circadian rhythm. We conclude that the sampling time is not critical for the assessment of oxidative DNA damage in urine.

[Neuroendocrine and renal effects of inorganic lead]. / Effetti neuroendocrini e renali del piombo inorganico.

In this study 371 workers occupationally exposed to inorganic Pb (range of blood lead concentrations, PbB: 100-800 microg/l) were examined in order to assess neuroendocrine and renal effects, with regard to exposure levels and ALAD polymorphism. Plasma prolactin, urinary excretion of plasmaproteins and renal tissue constituents were measured. None of such markers differed significantly between workers stratified according to PbB levels, except for heat-stable isoenzyme NAG-B: its very low prevalence of values above the upper reference limit increased significantly with increasing PbB. No significant differences were found in indicators by ALAD genotype. Our findings did not provide evidence of any renal and neuroendocrine effects in workers exposed to the current lead levels.

[Heme oxygenase 1 expression in foundry workers]. / Espressione dell'eme ossigenasi-1 in un gruppo di lavoratori di un'acciaieria.

Heme oxygenase 1 (HO-1) catalyses the oxidation of heme to biliverdin, and its expression is induced by oxidative stress. This study was aimed at assessing the role of metabolic polymorphisms (CYP1A1, CYP1B1, GSTM1, GSTP1, EPHX) in the modulation of HO-1 gene expression in 37 foundry workers. Blood and urine samples were obtained at the beginning (BS) and at the end (ES) of work shift, in February (T1) and June (T2). Urinary 1-hydroxypyrene (1-OHP) was measured as a tracer of PAH exposure. HO-1 gene expression in ES samples normalized to BS values (HO-1 ES/BS) was higher at T2 respect to T1. HO-1 gene induction was related to ES 1-OHP when considering either T2 samples or the combination of the two samplings. HO-1 ES/BS was significantly increased in subjects with at least a mutant allele for GSTP1 as compared to subjects with GSTP1AA genotype (1.23 +/- 0.002 vs 0.88 +/- 0.002, p < 0.05). Only in subjects with at least one vari.nt allele for GSTP1, a positive correlation between HO-1 ET/IT expression and 1-OHP FT levels was observed (r2 = 0.21, p = 0.016). The present study demonstrates a correlation between PAH exposure, as assessed by urinary 1-OHP, and the induction of HO-1 expression. Such a correlation seems to be limited to subjects bearing variant alleles for GSTP1. At the same exposure levels, these subjects showed a greater expression of HO-1 FT as compared to subjects with GSTP1 wild type genotype, possibly due to a higher oxidative stress in the subjects expressing the mutant GSTP1-1 isoform, which could imply a limited scavenging capacity.

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.

Determination of naphthalene metabolites in human urine by liquid chromatography-mass spectrometry with electrospray ionization.

The use of a liquid chromatography-electrospray mass spectrometry system was investigated for the quantitative analysis of naphthalene metabolites (alpha-naphthol, alpha-naphthylglucuronide and beta-naphthylsulphate) in untreated urine samples. Chromatography was carried out under ion-suppressed reversed-phase conditions, by using high-speed (3 cm, 3 microns) columns and formic acid (2 mM) as a modifier in the mobile phase. The ionization was obtained in the negative-ion mode. Linearity, sensitivity and precision of the method were explored by operating in selected-ion monitoring mode. The method was applied to the quantitative analysis of naphthalene metabolites in untreated urine samples from workers in a naphthalene producing plant. Solid-phase extraction was used for sample clean-up and trace enrichment. Liquid chromatography-tandem mass spectrometry experiments were performed for confirmation purposes.

Determination of free and glucuronated hexane metabolites without prior hydrolysis by liquid- and gas-chromatography coupled with mass spectrometry.

Since n-hexane metabolites are excreted as glucuronide conjugates, most conventional analytical procedures require preliminary hydrolysis, yielding to the 'total' 2,5-hexanedione (2,5-HD), but also giving rise to a number of artifacts. The whole pattern of n-hexane metabolites, both conjugated and unconjugated, as well as different methods of sample pretreatment have been evaluated by hyphenated techniques (liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS)). Aliquots of urine from rats exposed to n-hexane underwent enzymatic or acid hydrolysis or both; whereas one aliquot was applied to LC-MS, dichloromethane extracts were analyzed by GC-MS. In untreated urine, four glucuronides (-G) were identified and characterized by LC-MS: 2-hexanol-G, 5-hydroxy-2-hexanone-G, 4,5-dyhydroxy-2-hexanone-G, and 2,5-hexanediol-G. 'Free' 2,5-HD was detectable in non-hydrolyzed samples by both GC- and LC-MS. Whereas enzymatic hydrolysis did not increase the amount of 2,5-HD, acid hydrolysis led to increase 2,5-HD in variable amount and produced gamma-valerolactone as a result of a complete transformation of 4,5-dihydroxy-2-hexanone-G and the partial conversion from 5-hydroxy-2-hexanone-G. Further experiments showed that both 5-hydroxy-2-hexanone-G and 4,5-dihydroxy-2-hexanone-G, isolated by solid-phase extraction and hydrolyzed, yield comparable amount of 2,5-HD and gamma-valerolactone. In samples treated by acid hydrolysis, GC-MS only does not allow to understand the true source of 'total' 2,5-HD, which may be produced not only from 4,5-dihydroxy-2-hexanone-G but also from the more abundant 5-hydroxy-2-hexanone-G, which thus represents the main source of analytical artifacts. 'Free' 2,5-HD seems to be both suitable from an analytical point of view and meaningful for biological monitoring purposes, provided that conjugate metabolites are rapidly removed from the body leading to a negligible neurotoxic risk.

Biomarkers of dose and susceptibility in cyclists exposed to monoaromatic hydrocarbons.

A quasi-experimental field study was carried out in 24 volunteers with the aim of: (i) assessing personal exposure to aromatic hydrocarbons polluting urban areas; and (ii) exploring the role of polymorphic enzymes relevant to the biotransformation of benzene in the inter-individual variability of biomarkers. Each subject covered by bicycle: (i) inner city routes with often jammed traffic; and (ii) open rural routes. Time-weighted average airborne concentrations of benzene, toluene, ethylbenzene and xylenes (BTEX) were determined during 2-h runs. BTEX were determined by solid-phase micro-extraction (SPME) followed by gas chromatography coupled with mass spectrometry (GC-MS) in blood and spot urine samples collected just before and immediately after the runs. Urinary t,t-muconic acid was measured by high performance liquid chromatography (HPLC)-UV. Genotypes of epoxide hydrolase (EH) and glutathione-S-transferase class mu-1 (GSTM1) were also characterised. As compared to pre-run values, benzene and toluene in blood, and toluene and xylenes in urine significantly increased after urban runs. Urinary t,t-muconic acid was significantly higher in post-run samples after both urban (P < 0.001) and rural runs (P < 0.05). Despite a narrow range of exposure levels, a significant relationship was observed between airborne benzene and post-run t,t-muconic acid (r2 = 0.349, P < 0.00). When subgroups were distinguished according to EH and GSTM, subjects bearing both the EH wild type and GSTM 'null' genotype showed significant exposure-related changes in t,t-muconic acid excretion. Even at very low exposure levels, a 2-h bike run in a polluted urban environment may give rise to measurable changes in biomarkers of internal dose of selected aromatic hydrocarbons. Genetically-based metabolic differences may account for part of the inter-individual variability of biomarkers of exposure.

[Urinary excretion of 4-vinyl phenol after experimental and occupational exposure to styrene]. / Escrezione urinaria di 4-vinilfenolo dopo esposizione sperimentale e professionale a stirene.

Aim of this study was to assess the importance and the role of a minor metabolic route of styrene metabolism, involving the oxidation of the arene moiety of styrene, by means of the characterization of the conjugated urinary metabolites of 4-vinylphenol (4-VP). 4-vinylphenol-glucuronide (4-VP-G) and -sulfate (4-VP-S) were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) from 174 workers belonging to three cohorts recruited in European countries, and from 26 volunteers exposed to 50 mg/m3 (11.8 ppm) of styrene for 8 h. The 4-VP conjugates represented about 0.5-1% of the total excretion of styrene metabolites. Both 4-VP-G and 4-VP-S are eliminated with a mono-phasic kinetic, the glucuronide being excreted faster (half-time, 2.2 +/- 0.2 h) than the sulfate (half-time 9.7 +/- 1.7 h). The urinary 4-VP was found to be significantly correlated both with airborne styrene (r = 0.607, p < 0.001) and the sum of MA and PGA (r = 0.903, p < 0.001 in 'end-of-shift' samples). A measurable background excretion of 4-VP was also found in all urine samples from controls not occupationally exposed to styrene. This background appears to be highly correlated to smoking (p < 0.001). Consequently, the use of 4-VP as a biomarker of styrene exposure is recommended for exposures exceeding 1 ppm.

[Genetic polymorphism of biotransforming enzymes and genotoxic effects of styrenes]. / Polimorfismi genetici degli enzimi della biotrasformazione ed effetti genotossici dello stirene.

A cross-sectional study was carried out on laminators producing glass-fibre reinforced plastics, to evaluate the role of genetic polymorphism of xenobiotic metabolising enzymes on the genotoxicity of styrene. Clastogenic effects, evaluated by the micronucleus test, are related with end-of-shift urinary concentration of 4-vinylphenol and seem to be modulated by NQO1 polymorphism; aneuploidogenic effects, evaluated by the identification of centromers in micronuclei using the fluorescence in situ hybridisation technique with a pancentromeric probe, are related with before-shift urinary levels of mandelic and phenylglyoxylic acids and seem to be modulated by the GSTM1 polymorphism.

[Indicators of pulmonary epithelial damage among workers at a foundry exposed to airborne pollutants]. / Indicatori di danno epiteliale polmonare in lavoratori di una acciaieria elettrica esposti ad inquinanti aerodispersi.

Foundry ambient air contains very high concentrations of noxious substances, such as particulate matter and gaseous pollutants, which can target the respiratory epithelium. Serum concentrations of the 16-kDa Clara cell protein (CC16-S) may reflect both the integrity of the epithelial barrier and smoke-induced Clara cell toxicity. To evaluate whether CC16-S is a sensitive biomarker of early respiratory disturbances, it was determined in a group of 35 foundry male workers (aged 41.1 +/- 6.9 years) examined both prior to and at the end of their work-shift (06:00 a.m.-02:00 p.m.). Exposure to inhalable/respirable dusts and PAH was characterized; urinary excretion of 1-hydroxypyrene (1-OH-P) and naphtol was measured to assess exposure to pyrene and naphthalene, respectively. CC16 serum levels decreased at the end of the shift (10.7 +/- 3.82 micrograms/L vs. 8.39 +/- 3.05 micrograms/L; p < 0.01); such decrements were significantly larger in more exposed workers. Although smokers had lower baseline values as compared to non smokers, both subgroups showed an average decrease of 30% in CC16-S concentrations at the end of shift. CC16-S was also negatively correlated with 1-OH-P, but not with naphtol concentrations. Decreased CC16-S levels can result from citotoxicity and would represent an useful biomarker of pneumotoxicity in foundry workers exposed to complex mixtures.

[New biomarkers of exposure]. / Nuovi indicatori di esposizione.

In this paper we have defined the new biomarkers of exposure (NBE) as those biomarkers discovered in the last five years and, among previously validated biomarkers, also those applied in different ranges of doses or those determined in biological matrices which differ from matrices originally considered. We examined the results from the surveys carried out by the main Italian research units involved in biological monitoring, i.e. those from the Universities of Brescia, Milan, Naples, Padua, Parma, Pavia, Turin and Verona. The data were collected using a standardized model and included the following: type of element or organic compound, type of biomarker, analytical technique and method, their relationship with environmental monitoring data, their relationship with effect indicators or effects in general, improvement with respect to old biomarkers, reference values. Twenty two NBEs were identified: 14 elements and chemical compounds as such or as metabolites, 4 examples of mixtures, 3 of new matrices, one of speciation. Among the others, aspects such as interest in requiring NBE, quality assurance, availability, cost-benefit ratio were discussed. We conclude that development of this specific field of research appears to be a crucial point for future improvement in risk assessment and health surveillance procedures.

Linezolid levels in a patient with biliary tract sepsis, severe hepatic failure and acute kidney injury on sustained low-efficiency dialysis (SLED).

We report on a patient with biliary sepsis due to Vancomycin-resistant Enterococcus faecium (VRE) treated with linezolid (LNZ), who had both hepatic failure and acute kidney injury requiring daily sustained low-efficiency dialysis (SLED), a new intermittent, prolonged diffusive modality of renal replacement therapy for ICU patients. Following cholecystostomy and peritoneal drain insertion, serum, bile and peritoneal fluid serial samples were simultaneously collected for LNZ concentration measurement (chromatography/mass spectrometry). Unusually high serum antibiotic levels (20 mg/L or more) were achieved as early as 36 hours since the start of LNZ administration, owing to relatively low hepatic clearance. Serum LNZ leveled off after commencing SLED, apparently reaching steady state levels. The lowest values of Cmin in bile was 5.86 mg/L; the average serum and bile AUC0-12 over the observation period were 204 mg/L*h and 276 mg/L*h, with a AUC0-24/MIC ratio of 227 h and 307 h, respectively. The excellent biliary pharmacodynamic exposure suggests that standard-dose LNZ might represent a valuable choice in severe biliary infection, even in the presence of hepatic failure, when the patients receive highly efficient modalities of renal replacement therapy.