88 research outputs found
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
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
The protein pheromone Er-1 of the ciliate Euplotes raikovi stimulates humanT-cell activity: Involvement of interleukin-2 system
Water-soluble protein signals (pheromones) of the ciliate Euplotes have been supposed to be functional precursors of growth factors and cytokines that regulate cell–cell interactionin multi-cellular eukaryotes.This work provides evidence that native preparations of the Euplotes raikovi pheromone Er-1 (a helical protein of 40 aminoacids) specifically increases viability, DNA synthesis, proliferation, and the production of interferon-g, tumor necrosis factor-a, interleukin
(IL)-1b, IL-2, and IL-13 in human Jurkat T-cells. Also, Er-1 significantly decreases them RNA levels of the b and g subunits of IL-2 receptor(IL-2R), while them RNA levels of the a subunit appeared to be not affected. Jurkat T-cell treatments with Er-1 induced the down-regulation of
the IL-2Ra subunit by a reversible and time-dependent endocytosis, and increased the levels of phosphorylation of the extracellular signal-regulated kinases (ERK). The cell-type specificity of these effects was supported by the finding that Er-1, although unable to directly influence the
growth of human glioma U373 cells, induced Jurkat cells to synthesize and release factors that, in turn, inhibited the U373 cell proliferation. Overall, these findings imply that Er-1 coupling to IL-2R and ERK immuno-enhances T-cell activity, and that this effect likely translates to an inhibition of glioma cell growth
Determination of Plasma Antioxidant Power in Capillary Blood through the Innovative system PAT (Plasma Antioxidant Test)
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Exhaled Breath Condensate as a Suitable Matrix to Assess Lung Dose and Effects in Workers Exposed to Cobalt and Tungsten
The aim of the present study was to investigate whether exhaled breath condensate (EBC), a fluid formed by cooling exhaled air, can be used as a suitable matrix to assess target tissue dose and effects of inhaled cobalt and tungsten, using EBC malondialdehyde (MDA) as a biomarker of pulmonary oxidative stress. Thirty-three workers exposed to Co and W in workshops producing either diamond tools or hard-metal mechanical parts participated in this study. Two EBC and urinary samples were collected: one before and one at the end of the work shift. Controls were selected among nonexposed workers. Co, W, and MDA in EBC were analyzed with analytical methods based on mass spectrometric reference techniques. In the EBC from controls, Co was detectable at ultratrace levels, whereas W was undetectable. In exposed workers, EBC Co ranged from a few to several hundred nanomoles per liter. Corresponding W levels ranged from undetectable to several tens of nanomoles per liter. A parallel trend was observed for much higher urinary levels. Both Co and W in biological media were higher at the end of the work shift in comparison with preexposure values. In EBC, MDA levels were increased depending on Co concentration and were enhanced by coexposure to W. Such a correlation between EBC MDA and both Co and W levels was not observed with urinary concentration of either element. These results suggest the potential usefulness of EBC to complete and integrate biomonitoring and health surveillance procedures among workers exposed to mixtures of transition elements and hard metals
Climacostol reduces tumour progression in a mouse model of melanoma via the p53-dependent intrinsic apoptotic programme
Climacostol, a compound produced by the ciliated protozoan Climacostomum virens, displayed cytotoxic properties in vitro. This study demonstrates that it has anti-tumour potential. Climacostol caused a reduction of viability/proliferation of B16-F10 mouse melanoma cells, a rapidly occurring DNA damage, and induced the intrinsic apoptotic pathway characterised by the dissipation of the mitochondrial membrane potential, the translocation of Bax to the mitochondria, the release of Cytochrome c from the mitochondria, and the activation of Caspase 9-dependent cleavage of Caspase 3. The apoptotic mechanism of climacostol was found to rely on the up-regulation of p53 and its targets Noxa and Puma. In vivo analysis of B16-F10 allografts revealed a persistent inhibition of tumour growth rate when melanomas were treated with intra-tumoural injections of climacostol. In addition, it significantly improved the survival of transplanted mice, decreased tumour weight, induced a remarkable reduction of viable cells inside the tumour, activated apoptosis and up-regulated the p53 signalling network. Importantly, climacostol toxicity was more selective against tumour than non-tumour cells. The anti-tumour properties of climacostol and the molecular events associated with its action indicate that it is a powerful agent that may be considered for the design of pro-apoptotic drugs for melanoma therapy
Bioactivity and Structural Properties of Novel Synthetic Analogues of the Protozoan Toxin Climacostol
Climacostol (5-[(2Z)-non-2-en-1-yl]benzene-1,3-diol) is a resorcinol produced by the protozoan Climacostomum virens for defence against predators. It exerts a potent antimicrobial activity against bacterial and fungal pathogens, inhibits the growth of several human and rodent tumour cells, and is now available by chemical synthesis. In this study, we chemically synthesized two novel analogues of climacostol, namely, 2-methyl-5 [(2Z)-non-2-en-1-yl]benzene-1,3-diol (AN1) and 5-[(2Z)-non-2-en-1-yl]benzene-1,2,3-triol (AN2), with the aim to increase the activity of the native toxin, evaluating their effects on prokaryotic and free-living protists and on mammalian tumour cells. The results demonstrated that the analogue bearing a methyl group (AN1) in the aromatic ring exhibited appreciably higher toxicity against pathogen microbes and protists than climacostol. On the other hand, the analogue bearing an additional hydroxyl group (AN2) in the aromatic ring revealed its ability to induce programmed cell death in protistan cells. Overall, the data collected demonstrate that the introduction of a methyl or a hydroxyl moiety to the aromatic ring of climacostol can effectively modulate its potency and its mechanism of action
Composition of Metallic Elements and Size Distribution of Fine and Ultrafine Particles in a Steelmaking Factory
Background: The characteristics of aerosol, in particular particle size and chemical
composition, can have an impact on human health. Particle size distribution and chemical
composition is a necessary parameter in occupational exposure assessment conducted in order
to understand possible health effects. The aim of this study was to characterize workplace airborne
particulate matter in a metallurgical setting by synergistically using two different approaches;
Methodology: Analysis of inhalable fraction concentrations through traditional sampling equipment
and ultrafine particles (UFP) concentrations and size distribution was conducted by an Electric
Low-Pressure Impactor (ELPI+™). The determination of metallic elements (ME) in particles was
carried out by inductively coupled plasma mass spectrometry; Results: Inhalable fraction and ME
concentrations were below the limits set by Italian legislation and the American Conference of
Governmental Industrial Hygienists (ACGIH, 2017). The median of UFP was between 4.00 104
and 2.92 105 particles/cm3. ME concentrations determined in the particles collected by ELPI show
differences in size range distribution; Conclusions: The adopted synergistic approach enabled a
qualitative and quantitative assessment of the particles in steelmaking factories. The results could
lead to a better knowledge of occupational exposure characterization, in turn affording a better
understanding of occupational health issues due to metal fumes exposure
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