Reference ranges of urinary biomarkers of oxidized guanine in (2'-deoxy)ribonucleotides and nucleic acids

This study was aimed at defining the reference ranges for biomarkers of oxidized guanine in (2'-deoxy)ribonucleotides and nucleic acids from a large Italian sample. We recruited 300 healthy subjects (150 males; mean age 44.1±13.6years; 26% smokers) without any known exposure to occupational oxidizing agents. They were asked to provide a spot urine sample, on which the following markers were determined by liquid chromatography-tandem mass spectrometry: 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), 8-oxo-7,8-dihydroguanine (8-oxoGua), and cotinine. The reference ranges, estimated as the 5th-95th percentiles of creatinine-normalized values (pmol/μmol(creat)) were 0.7-4.2, 0.9-4.7, and 5.6-120.7 for 8-oxodGuo, 8-oxoGuo, and 8-oxoGua, respectively. Oxidation biomarkers were correlated with one another (p<0.005) and with urinary creatinine (p<0.0001). Males excreted significantly higher concentrations of 8-oxoGua than females (p<0.0001). 8-OxoGua and 8-oxoGuo showed a positive association with age (p<0.001), also after stratification by gender. Multiple linear regression models including urinary creatinine concentration, age, and smoking habit as independent variables showed a significant effect of age, but not of smoking, on the levels of 8-oxoGuo in males (p<0.0001) and of both 8-oxoGuo and 8-oxoGua in females (p<0.0001). A preliminary assessment in a small group (n=25) of patients affected by advanced non-small-cell lung cancer and receiving platinum-based chemotherapy showed significantly higher values of both 8-oxoGuo and 8-oxodGuo (p<0.0001 for both) compared to the referent population.     

Alteration of steroid hormone sulfation andd-glucaric acid excretion in lead workers

The capability of lead to interfere with the first and/or second phase of enzymatic reaction of biotransformation has been investigated in ten lead workers and in ten controls by studying the steroid hormone sulfation andd-glucaric acid (GA) urinary excretion. No statistical differences have been found for the total amount of urinary steroids, whereas a decrease of about 50% was observed for the sulfated fraction in lead workers. The mean value for the GA excretion in the exposed subjects (1.8±0.7 mmol/mol creatinine) was significantly lower than in the control group (4.4±0.8 mmol/mol creatinine). In spite of the small number of investigated subjects, it can be hypothesized that an interaction of lead with sulfotransferase exists. The decreased GA excretion does not prove an altered activity of microsomal enzymes, although inhibition of microsomal activity following lead exposure was previously reported.     

Metallic elements in exhaled breath condensate and serum of patients with exacerbation of chronic obstructive pulmonary disease

Biomarkers in exacerbated chronic obstructive pulmonary disease may be useful in aiding diagnosis, defining specific phenotypes of disease, monitoring the disease and evaluating the effects of drugs. The aim of this study was the characterization of metallic elements in exhaled breath condensate and serum as novel biomarkers of exposure and susceptibility in exacerbated chronic obstructive pulmonary disease using reference analytical techniques. C-Reactive protein and procalcitonin were assessed as previously validated diagnostic and prognostic biomarkers which have been associated with disease exacerbation, thus useful as a basis of comparison with metal levels. Exhaled breath condensate and serum were obtained in 28 patients at the beginning of an episode of disease exacerbation and when they recovered. Trace elements and toxic metals were measured by inductively coupled plasma-mass spectrometry. Serum biomarkers were measured by immunoassay. Exhaled manganese and magnesium levels were influenced by exacerbation of chronic obstructive pulmonary disease, an increase in their concentrations--respectively by 20 and 50%--being observed at exacerbation in comparison with values obtained at recovery; serum elemental composition was not modified by exacerbation; serum levels of C-reactive protein and procalcitonin at exacerbation were higher than values at recovery. In outpatients who experienced a mild-moderate chronic obstructive pulmonary disease exacerbation, manganese and magnesium levels in exhaled breath condensate are elevated at admission in comparison with values at recovery, whereas no other changes were observed in metallic elements at both the pulmonary and systemic level.     

Health conditions of bus drivers in a 6 year follow up study

The bus drivers of a public bus company, working in a fast rotating 4 shift system from 05.00 to 24.30, were examined in 1993 (230 persons) and 1999 (266 persons). The comparison between the two years showed no significant differences for all the parameters evaluated by the Standard Shiftwork Index and medical examination. In both surveys work organisation was considered "efficient-fairly good" by most workers, who were mostly satisfied with their job. Work load was rated significantly higher for "afternoon" and "morning" shifts, during which most accidents at work and "in itinere" occurred. Night sleep was reduced by 3 hours on "early" shift and about 2 hours on "morning" shifts. The most prevalent health troubles dealt with low back pain, gastritis, headache and haemorrhoids. Neuroticism was the trait more correlated with poorer health conditions, whereas shiftwork exposure appeared as a significant predictor of risk of critical Effort/Reward Imbalance and minor psychological disorders. Both extrinsic and intrinsic efforts significantly increased with age, but not reward. The comparison of the same cohort of 108 persons examined both in 1993 and in 1999 showed a significant increase of low back pain, gastrointestinal troubles, haemorrhoids and lipids disorders.     

Interference of Manganese on neuroendocrinal system in exposed workers

The neurotoxic effects of Manganese (Mn) are well known, and are usually caused by high occupational exposure over long periods of time. The effects caused by low doses of this metal have been poorly evaluated. For this reason, we decided to evaluate neuroendocrinal tests in a group of 14 male workers employed in a ferrousmanganese foundry (exposed to Mn air concentrations within the TLV-TWA) and in 14 male control subjects, by analyzing FSH, LH, prolactin, and cortisol. The urinary Mn, prolactin, and cortisol levels were significantly higher in the worker’s group. The preliminary results of this research seem to show that for exposure below the TLV, Mn can somehow interfere with the neuroendocrine system. In order to confirm the existence of these effects and to verify their possible correlation with the dopaminergic control system, further studies are necessary.     

Focal adhesion molecules as potential target of lead toxicity in NRK-52E cell line

In this study, we investigated the influence of inorganic lead (Pb(II)), an environmental pollutant having nephrotoxic action, on the focal adhesion (FA) organization of a rat kidney epithelial cell line (NRK-52E). In particular, we evaluated the effects of the metal on the recruitment of paxillin, focal adhesion kinase, vinculin and cytoskeleton proteins at the FAs complexes. We provided evidences that, in proliferating NRK-52E cell cultures, low concentrations of Pb(II) affect the cell adhesive ability and stimulate the disassembly of FAs, thus inhibiting the integrin-activated signalling. These effects appeared to be strictly associated to the Pb-induced arrest of cell cycle at G0/G1 phase also proved in this cell line.     

Resistance to cadmium salts and metal absorption by different microbial species

The present study evaluates the inhibitory activity and the absorption of cadmium (Cd) salts by different microbial species, including Gram-positive (Staphylococcus aureus andS. epidermidis), Gram-negative (Pseudomonas aeruginosa, Escherichia coli, Salmonella typhimurium, andProteus mirabilis) bacteria and one yeast (Candida albicans). The metal absorption by growing cells was considered both in liquid and in solid medium. For one strain ofP. aeruginosa the presence of Cd deposits inside the cell was investigated by transmission electron microscopy. Generally, the Gram-negative species tested proved to be highly resistant to Cd ions and accumulated great amounts of Cd during growth. Two strains ofP. aeruginosa showed a high degree of resistance to Cd and were particularly efficient in removing the metal from solutions. The Gram-positive bacteria showed a heterogeneous behavior: anS. aureus strain susceptible to Cd absorbed, at low metal concentrations, higher amounts of metal than a Cd-resistant one. The metal absorption for Gram-negative species was dose dependent, while for the Cd-resistant staphylococci it reached a plateau. Our results suggest that microorganisms can represent a good model to study the interactions between heavy metals and living organisms.