Biomedical subjects

Enrico Sabbioni

Publications and source records attributed to Enrico Sabbioni.

27 records · Page 2Linked to original sources

PubMed2003

Preparation of "high specific activity" radiochemical forms of vanadium, manganese and thallium for metallo-toxicological studies.

In this paper are presented the production methods for very "high specific activity" radionuclides (HSA-RN) of vanadium, manganese and thallium which have been developed in our laboratories for labelling different chemical forms of these elements present in the echo-systems in ultra-trace amounts, for metallo-toxicological and bio-kinetic studies. Use was made of both cyclotron and thermal nuclear reactor. If the nuclear reaction product has atomic number different from irradiated target, it is possible separating the radioactive nuclide from irradiated target, without addition of isotopic carrier. This kind of radionuclide is named No Carrier Added, NCA, and his specific activity, As is very high and can reach values close to the theoretical Carrier Free one, CF. The experimental determination of specific activity, chemical and radiochemical purities is mandatory for all these kinds of applications.

Cyclotrons↗

PubMed2003

In vitro effects of nickel-sulphate on immune functions of normal and nickel-allergic subjects: a regulatory role for zinc.

Nickel hypersensitivity represents a very common human disease state, mainly occurring in females, defined as allergic contact dermatitis. Ni is a transition metal whose activity may be modulated by congeners. Zinc, an essential component for living organisms, has been shown to counteract Ni effects in patients with Ni hypersensitivity. We analysed immune responses to both Ni and Zn in healthy subjects and patients with allergic contact dermatitis to Ni. Our in vitro results show that Ni modulates surface receptors expression, reduces phytohemagglutinin (PHA)-driven lymphoproliferation, and upregulates some proinflammatory cytokines production, including interferon (IFN)-gamma. Zn also induced CD4+ lymphocyte proliferation, but it abolished or reduced most Ni-mediated effects. Our data are consistent with the hypothesis that Zn and Ni, as part of the heavy transition metals, may exchange roles in immune-mediated phenomena leading to expression of allergic contact dermatitis.

Adult↗

PubMed2002

Thin-target excitation functions, cross-sections and optimised thick-target yields for natMo(p,xn)(94g ,95m,95g,96(m + g))Tc nuclear reactions induced by protons from threshold up to 44 MeV. No Carrier Added radiochemical separation and quality control.

This work describes the method adopted in our laboratories, to produce 94gTc, 95gTc, 95mTc and 96gTc radionuclides via proton-cyclotron irradiation on molybdenum targets of natural isotopic composition. A new set of experimental thin-target excitation functions and "effective" cross-sections for direct natMo(p,xn)(A)Tc [with A = 94, 95, 95, 96] nuclear reactions, with incident proton energy in the range from threshold up to 44 MeV is presented. Some definitions of the equations used and nuclear data traceability are reported. Thick-target yield values were calculated and optimised, by numerical fitting and integration of the measured excitation functions. These values allow optimisation of production yield of one radionuclide, minimising at the same time the yield of the others. Radiochemical separation on NCA technetium radionuclides from both molybdenum target and niobium, zirconium and yttrium radioactive by-products is reported. Quality control tests of the radiotracers were developed for the applications envisaged in environmental metallo-biochemical toxicology.

Journal Article↗

PubMed2002

Cytogenetic and oxidative damage induced in human lymphocytes by platinum, rhodium and palladium compounds.

This study of soluble compounds of platinum, palladium and rhodium investigated the genotoxic properties of (NH(4))(2)PtCl(4), PtCl(2), PtCl(4), (NH(4))(2)PdCl(4), PdCl(2) and RhCl(3) using the human lymphocyte micronucleus (MN) assay coupled with fluorescence in situ hybridization (FISH). A pancentromeric DNA probe was used to detect both centromere-positive micronuclei (C+ MN) as well as centromere-negative micronuclei (C- MN). A modified alkaline single cell gel electrophoresis (SCGE) assay was used to evaluate the possible role of oxidative damage in genotoxicity of the Pt, Pd and Rh compounds tested. Two enzymes, endonuclease III and formamidopyrimidine glycosylase, were used to recognize and subsequently cut oxidized pyrimidines and purines, respectively. A significant induction of MN by Pt and Rh compounds was observed compared with controls, while (NH(4))(2)PdCl(4) and PdCl(2) displayed weak significant MN induction. The FISH technique revealed no significant difference in the frequency of C+ MN and C- MN for all compounds tested. These findings suggest that MN induction is due both to a clastogenic and an aneuploidogenic mechanism. SCGE detected an increase in the level of DNA oxidative damage for the Rh compound and for Pt(IV) which was also capable of inducing an increase in primary DNA damage at all the tested doses. This work highlights the stronger genotoxicity, likely mediated by oxidative damage induction, of Pt and Rh compounds compared with Pd salts.

Cells, Cultured↗

PubMed2002

In vitro effects of vanadate on human immune functions.

Vanadium (V) is an element with wide industrial applications and environmental release. The object of this study was to determine the in vitro effects of high (10(-4) M) and low (10(-7) M) concentrations of sodium metavanadate (NaVO3) on cultured peripheral blood mononuclear cell (PBMC) proliferation, cytokine release, CD expression, and granulocyte O2- production. At 10(-4) and 10(-7) M, NaVO3 did not modify PBMC proliferation in the absence of phytohemagglutinin (PHA). On the other hand, 10(-4) M NaVO3 reduced by -25% the PBMC proliferation in PHA-stimulated cultures, with a significant reduction of the stimulation index (SI) of blastogenesis. Moreover, 10(-4 M NaVO3 significantly reduced the release of IFN-gamma by PHA-stimulated PBMCs, and 10(-7) M NaVO3 significantly enhanced the release of TNF-alpha. In addition, IL-5 release was significantly inhibited by high concentration of sodium metavanadate and significantly enhanced by low concentration of NaVO3. Neither 10(-4) nor 10(-7) M NaVO3 modified the expression of CD3+, CD4+, CD8+, or CD56+ in PHA-stimulated and unstimulated lymphocytes. Finally, 10(-4) M NaVO3 reduced the granulocyte production of O2- by about 70%, while 10(-7) vanadate reduced its production to a lesser extent. These results show that 10(-4) M NaVO3 exerts inhibitory effects on PBMCs, while at 10(-7) M it exerts a stimulatory action with a slight shift of the immune response towards a Th2-type response. This investigation suggests that environmental V can have important effects on the human immune system.

Adult↗

PubMed2002

Gene expression in Xenopus embryos after methylmercury exposure: a search for molecular biomarkers.

Mercury is a major issue in environmental health, as it can be biotransformed to methylmercury, accumulate into aquatic organisms, and enter the food chain. Therefore, we searched for molecular markers for methylmercury exposure comparing, by differential display, exposed Xenopus embryos to controls. We found two genes whose expression is completely inhibited by CH3HgCl, and we propose them as biomarkers of exposure. The first transcript appears to be a novel gene, with a short region similar to the human iron-sulfur subunit of succinate dehydrogenase. The second gene presents a high similarity with the human homeodomain-interacting protein kinase 3 (HIPK3), a protein that is known to be involved in the apoptotic signaling pathway. These molecular biomarkers could be used to detect very early effects of the metal; furthermore, they could be useful in understanding the molecular mechanisms of mercury toxicity.

Animals↗

PubMedDate not supplied

A comparative study of the toxicity of mercury dichloride and methylmercury, assayed by the Frog Embryo Teratogenesis Assay--Xenopus (FETAX).

The Frog Embryo Teratogenesis Assay-Xenopus (FETAX) is a powerful and flexible bioassay that makes use of the embryos of the anuran amphibian Xenopus laevis. The FETAX can detect xenobiotics that affect embryonic development, when mortality, teratogenicity and growth inhibition are used as endpoints. The FETAX was used to compare the embryotoxic and teratogenic potentials of two chemical species of mercury, inorganic mercury(II) chloride (HgCl2) and organic methylmercury chloride (MeHgCl). A higher toxicity of MeHgCl (the estimated median lethal concentration [LC50] and median teratogenic concentration [TC50] were 0.313microM and 0.236microM, respectively) over HgCl2, with estimated LC50 and TC50 values of 0.601microM and 0.513microM, respectively). On the basis of these results, HgCl2 and MeHgCl can be classified as "slightly teratogenic compounds", as the ratio of LC50/TC50 is less than 1.5. There was a significant deviation from the commonly described monotonic behaviour of the concentration-response curves, suggesting a hormetic effect of both species of mercury. Uptake experiments, followed by neutron activation analysis, showed a higher incorporation of mercury in embryos exposed to MeHgCl compared with those exposed to HgCl2. Interestingly, Hg- exposed embryos showed a higher content of selenium and zinc than did control embryos.

Abnormalities, Drug-Induced↗

PubMedDate not supplied

In vitro setting of dose-effect relationships of 32 metal compounds in the Balb/3T3 cell line, as a basis for predicting their carcinogenic potential.

The results are reported of the second stage in a programme for a systematic in vitro study on the carcinogenic potential of metal compounds with Balb/3T3 clone A31-1-1 mouse fibroblasts. Nineteen metal compounds that exhibited a strong cytotoxic effect during a previous screening run with a 100 microM fixed dose were tested with a 72-hour exposure over a wide range of concentrations (from 0.1 microM to 1000 microM), to produce dose-effect curves to permit extrapolation of the 50% inhibition concentration (IC50) values for each metal compound. This allows the establishment of a suitable range of doses for individual metal species, for use in the subsequent Balb/3T3 assay based on a two-stage concurrent cytotoxicity and morphological transformation protocol. Another 13 metal compounds were also tested, to determine whether the Balb/3T3 cell transformation assay is really a valuable in vitro model in relation to the problem of metal speciation. Of the metal compounds assayed, 26 showed a dose related cytotoxic response with calculated IC50 values ranging from 0.25 microM (CH3HgCl) to 140 microM [(C5H5)2TiCl2], whereas six metal compounds, namely (NH4)6Mo7O24*4H2O, CH3AsO(OH)2, C2H6AsNaO2(3H2O, KBr, CrCl3*6H2O and (NH4)2[TiO(C2O4)2]*H2O, displayed no observable cytotoxicity or low cytotoxicity at all the doses tested. The determination of IC50 values permits a ranking of the cytotoxicity responses of metal compounds with the highest cytotoxicities. Dose-effect curves and IC50 values of different chemical forms of individual metal compounds of As, Br, Cr, Hg, Ir, Pt, Te, Ti and V (cationic/anionic inorganic or organometallic species) showed clearly how the chemical nature of the metal strongly influences the toxic response. This confirms that the Balb/3T3 cell line is a valuable in vitro model with respect to the problem of metal speciation. This is a fundamental aspect to be considered when incorporating the results from in vitro cell transformation assays of the carcinogenic potential of metal compounds into regulatory testing schemes. In this context, the choice of test metal species for the development and validation of such assays cannot disregard the possibility that humans will be exposed to specific chemical forms of individual metal compounds (different oxidation states, and inorganic or organometallic natures) that can profoundly affect their toxicity.

3T3 Cells↗

PubMedDate not supplied

Arsenic toxicity and HSP70 expression in Xenopus laevis embryos.

The evaluation of the effect of trace metals on health can be difficult, because of their presence in the environment in various chemical forms. Exposure to arsenic compounds is an example of this complexity, as it can be present in the environment in inorganic and organic forms. The effects of arsenic in vertebrates are complicated by several variables, such as speciation of the element, the exposure route, and the susceptibility of the particular animal species. The embryotoxicity and teratogenicity of three arsenic species - sodium arsenite (NaAsO(2)), disodium hydrogen arsenate (Na(2)HAsO(4)) and dimethylarsinic acid [(CH3)2AsOOH] - were evaluated by the modified frog embryo teratogenic assay on Xenopus (FETAX). We also show how the classical FETAX endpoints, based on morphological and morphometrical analysis, can conveniently be integrated with the study of molecular markers. Possible changes in the expression of the mRNA for the heat-shock protein HSP70, following exposure to NaAsO(2), were examined by using the reverse transcriptase polymerase chain reaction. HSP70 mRNA is strongly induced by arsenic.

Abnormalities, Drug-Induced↗