The Role of Albumin in Human Toxicology of Cobalt: Contribution from a Clinical Case

The distribution and adverse effects, especially to optic and acoustic nerves, of cobalt released from a hip arthroplasty and its association with albumin were studied. The analysis of cobalt was performed in plasma, whole blood, urine, and cerebrospinal fluid by inductively coupled plasma mass spectrometry (ICP-MS). The fraction of albumin binding the metal was determined by colorimetric assay using dithiothreitol (DTT). In all the biological matrices very high levels of cobalt were measured, but contrary to expected, a higher concentration in whole blood than in plasma was observed. The determination of altered albumin confirmed this hypothesis. This evidence might indicate an alteration in the binding of cobalt to albumin and a consequent increase in the concentration of the diffusible (free) fraction of the metal. This appears an interesting starting point for further investigations for identifying and better understanding cobalt neurotoxicity, apparently not so frequent in occupational medicine and clinical practice

Cobalt, chromium and molybdenum ions kinetics in the human body: data gained from a total hip replacement with massive third body wear of the head and neuropathy by cobalt intoxication.

6openopenPazzaglia, U; Apostoli, P; Congiu, T; Catalani, S; Marchese, M; Zarattini, G.Pazzaglia, Ugo; Apostoli, Pietro; Congiu, T; Catalani, S; Marchese, M; Zarattini, Guid

Polychlorinated biphenyl serum levels in subjects with hepatocellular carcinoma as compared with the general population

Background. Polychlorinated biphenyls (PCBs) have been recognized as human carcinogens and cause liver cancer in animal experimental studies. However, no study investigated their association with hepatocellular carcinoma (HCC) so far. This study aimed to evaluate the serum PCB concentration in HCC patients and in healthy subjects of the general population living in Brescia, North Italy, a highly industrialized area with heavy PCB environmental pollution due to the presence of a PCB producing factory. Methods. Lipid-adjusted PCB concentrations, computed as the sum of 24 congeners, were measured in the serum of 101 HCC patients and in 101 healthy subjects of the same age and gender. Results. Hepatitis B and C virus infection and history of heavy alcohol intake were found, alone and combined, in 87% of HCC patients. No difference was found in PCB serum concentration of HCC patients with and without, and according to, the major risk factors for liver disease. No significant difference was observed in serum total PCB concentration between HCC patients (median: 1081; range: 287.0-3182.0 ng/g lipid) and healthy subjects (median: 1199.3; range: 225.7-22825 ng/g lipid). PCB congeners 118, 138, 153, 156, 180 and 194 were the only ones found over the detection limit in at least 30% of HCC patients. The serum level of PCB 118, but not that of other congeners, was higher in HCC patients than in healthy subjects. Conclusion. These findings do not support the hypothesis that PCBs play an important role in HCC development, although a contribution by some specific congeners cannot be ruled ou

Is age more than manual material handling associated with lumbar vertebral body and disc changes? A cross-sectional multicentre MRI study

Conflicting evidence exists to what extent manual material handling (MMH) causes lumbar disc disease, lack of evidence exist that this effect takes place especially at L5-S1 level, where the greatest moment occurs. The aim was to assess if lumbar vertebral body and disc changes are more common in people whose job involves significant MMH and, if so, to evaluate if lumbar vertebral body and disc changes are more prevalent in the lower part of the lumbar spine (L4-L5 and L5-S1)

Free copper in serum: An analytical challenge and its possible applications

Copper (Cu), as an essential metal, plays a crucial role in biochemical reactions and in physiological regulations

Effects of airborne pollutants on mitochondrial DNA Methylation

Background: Mitochondria have small mitochondrial DNA (mtDNA) molecules independent from the nuclear DNA, a separate epigenetic machinery that generates mtDNA methylation, and are primary sources of oxidative-stress generation in response to exogenous environments. However, no study has yet investigated whether mitochondrial DNA methylation is sensitive to pro-oxidant environmental exposures. Methods: We sampled 40 male participants (20 high-, 20 low-exposure) from each of three studies on airborne pollutants, including investigations of steel workers exposed to metal-rich particulate matter (measured as PM1) in Brescia, Italy (Study 1); gas-station attendants exposed to air benzene in Milan, Italy (Study 2); and truck drivers exposed to traffic-derived Elemental Carbon (EC) in Beijing, China (Study 3). We have measured DNA methylation from buffy coats of the participants. We measured methylation by bisulfite-Pyrosequencing in three mtDNA regions, i.e., the transfer RNA phenylalanine (MT-TF), 12S ribosomal RNA (MT-RNR1) gene and “D-loop” control region. All analyses were adjusted for age and smoking. Results: In Study 1, participants with high metal-rich PM1 exposure showed higher MT-TF and MT-RNR1 methylation than low-exposed controls (difference = 1.41, P = 0.002); MT-TF and MT-RNR1 methylation was significantly associated with PM1 exposure (beta = 1.35, P = 0.025); and MT-RNR1 methylation was positively correlated with mtDNA copy number (r = 0.36; P = 0.02). D-loop methylation was not associated with PM1 exposure. We found no effects on mtDNA methylation from air benzene (Study 2) and traffic-derived EC exposure (Study 3). Conclusions: Mitochondrial MT-TF and MT-RNR1 DNA methylation was associated with metal-rich PM1 exposure and mtDNA copy number. Our results suggest that locus-specific mtDNA methylation is correlated to selected exposures and mtDNA damage. Larger studies are needed to validate our observations

Modulation of cell growth and cisplatin sensitivity by membrane gamma-glutamyltransferase in melanoma cells.

The plasma membrane enzyme c-glutamyltransferase (GGT) is regarded as critical for the maintenance of intracellular levels of glutathione (GSH). GGT expression has been implicated in drug resistance through elevation of intracellular GSH. The dependence of intracellular GSH on GGT expression was not conclusively ascertained. The present study was designed to investigate the role of GGT and of intracellular GSH levels in modulating proliferation and sensitivity to cisplatin of melanoma cells. GGT transfection resulted in increased growth, both in vitro and in tumour xenografts. In addition, GGT-transfected cells exhibited reduced sensitivity to cisplatin associated with lower DNA platination. A decrease in intracellular GSH levels, rather than an increase, was observed in GGT-transfected cells; moreover, in cysteine-deficient conditions, the expression of GGT did not provide transfected cells with the ability of utilising extracellular GSH. In conclusion, these results indicate that GGTactivity confers a growth advantage unrelated with intracellular glutathione supply, and are consistent with the interpretation that cisplatin resistance is the consequence of modifications of cellular pharmacokinetics as a result of extracellular drug inactivation by thiol metabolites originated by GGT-mediated GSH cleavage

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

AbstractIn 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