Effect of Ni(II), Cd(II) and Al(III) on human fibroblast bioenergetics, a preliminary comparative study

International audienceExposure to Ni, Cd or Al leads to different health issues depending on the dose and the exposure frequency. Their mechanism of action is poorly known, but as metals, they may have some points in common. The aim of this work was to compare the impact on cell bioenergetic of these metals using a common cell model: a normal human dermal fibroblast (NHDF) in primary culture. To study cell bioenergetics which ''concerns energy conservation and conversion processes in a living cell'' as defined by Demirel and Sandler, two technics are combined: oximetry and microcalorimetry. The heat flow measured by microcalorimetry reflects cell metabolism and more generally glucose catabolism (the only nutriment brought to the NHDF). Cell respiration is measured by oximetry and shows the impact on the mitochondria, the energy factory of the cell. Without incubation, Cd inhibits thermogenesis and cell respiration, Ni has no effect, and Al inhibits cell respiration but not thermogenesis. After 24 h of contact at 40 lM, NHDF died with Cd but seemed over-activated with Al and Ni (thermogenesis and cell respiration increased)

Logarithmic periodicities in the bifurcations of type-I intermittent chaos

The critical relations for statistical properties on saddle-node bifurcations are shown to display undulating fine structure, in addition to their known smooth dependence on the control parameter. A piecewise linear map with the type-I intermittency is studied and a log-periodic dependence is numerically obtained for the average time between laminar events, the Lyapunov exponent and attractor moments. The origin of the oscillations is built in the natural probabilistic measure of the map and can be traced back to the existence of logarithmically distributed discrete values of the control parameter giving Markov partition. Reinjection and noise effect dependences are discussed and indications are given on how the oscillations are potentially applicable to complement predictions made with the usual critical exponents, taken from data in critical phenomena.Comment: 4 pages, 6 figures, accepted for publication in PRL (2004

La calorimétrie et la santé

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Effect of Ni(II), Cd(II) and Al(III) on human fibroblast bioenergetics, a preliminary comparative study

International audienceExposure to Ni, Cd or Al leads to different health issues depending on the dose and the exposure frequency. Their mechanism of action is poorly known, but as metals, they may have some points in common. The aim of this work was to compare the impact on cell bioenergetic of these metals using a common cell model: a normal human dermal fibroblast (NHDF) in primary culture. To study cell bioenergetics which ''concerns energy conservation and conversion processes in a living cell'' as defined by Demirel and Sandler, two technics are combined: oximetry and microcalorimetry. The heat flow measured by microcalorimetry reflects cell metabolism and more generally glucose catabolism (the only nutriment brought to the NHDF). Cell respiration is measured by oximetry and shows the impact on the mitochondria, the energy factory of the cell. Without incubation, Cd inhibits thermogenesis and cell respiration, Ni has no effect, and Al inhibits cell respiration but not thermogenesis. After 24 h of contact at 40 lM, NHDF died with Cd but seemed over-activated with Al and Ni (thermogenesis and cell respiration increased)

Direct DNA interaction and genotoxic impact of three metals: Cadmium, nickel and aluminum

International audienceThis study simultaneously investigates direct DNA interaction and genotoxic impact of three typical metals: aluminum, cadmium and nickel, which the high concentration in soils and which the industries use, result in a daily significant exposure to humans. The three of them are suspected to be involved in carcinogenesis which implies genomic lesions. We propose to first study their genotoxic impact in vivo on primary normal human dermal fibroblast (NHDF) cells with comet assay at pH 7 to measure DNA breaks occurrence. Then, to characterize the metal/DNA interaction by isothermal titration calorimetry (ITC). Comet assay shows that Cd and Ni are genotoxic, they are responsible for DNA breaks starting from 1.10-4 mol.L-1 and 5.10-2 mol.L-1, respectively whereas Al has no effect (on DNA at pH7) as studied by ITC at pH 7. Cd and Ni present an electrostatic interaction with DNA phosphate groups. At high Cd concentration, a DNA condensation is observed by contrast. Al has no interaction with DNA phosphate groups, but at pH 4 the electrostatic interaction is strong and the same DNA condensation phenomenon is observed. Metal genotoxic effect seems linked to the electrostatic interaction on DNA phosphate groups. Genotoxic power evolves in parallel to DNA phosphate interaction strength as Cd > Ni > Al. If this study shows that metals do not directly break DNA, this binding could be a preferential site for damage due to reactive oxygen species

Detection of Rhodamine 6G at low concentrations using Raman Spectroscopy: A comparison between Ag and Au-based nanoporous substrates

International audienceThe detection of R6G on nanoporous susbtrates at low concentrations (10(-4) M 1.10(-6) M, it was evidenced that R6G Raman response does not depend on metal chemical nature. It is linearly correlated to R6G adsorbed amounts, evidencing the pre-concentration property of the substrates. For lower concentrations, differences were observed in Raman responses. For C = 1.10(-6) M, the Raman bands of R6G adsorbed on SiO2 and Au@SiO2 are similar to those found at higher concentrations. For Ag@SiO2, two new bands, corresponding to bending modes of ethylamine groups, are present as well as the band related to Ag-N stretching mode. This was explained by the specific interaction developed between R6G and Ag@SiO2. For C = 1.10(-7) M, only the two bands related to R6G ethylamine groups are present for all substrates and a Raman signal enhancement was found for Ag-based substrate

Adsorption properties, the pH-sensitive release of 5-fluorouracil and cytotoxicity studies of mesoporous silica drug delivery matrix

International audienceMesoporous silica materials were investigated as the carriers for pH-sensitive drug delivery systems. Porous silica SBA-15 was first functionalized by anchoring N-[3-(trimethoxysilyl) propyl] aniline groups on the surface. After loading of an antineoplastic agent 5-fluorouracil, the pores were capped by β-cyclodextrin molecules. The studied samples were characterized by N 2 adsorption/desorption measurements, thermal analysis, powder X-Ray Diffraction, and Transmission Electron Microscopy. Adsorption properties of 5-fluorouracil were explored via the construction of adsorption isotherms. The amount of 5-FU adsorbed on amine-functionalized SBA-15 was 60 mg per 1 g of solid. The adsorption of 5-fluorouracil on silica was also monitored by microcalorimetry, showing low adsorption enthalpies. Drug release properties from matrices were studied using UV-Visible spectroscopy with the un-blocked and blocked pores configuration to demonstrate the efficiency of the pH-responsive nanovalves and evaluated using different kinetic models. It was shown that no drug release occurred at neutral pH and that more than 80% of drug adsorbed amount was released at pH = 5. Working at the equilibrium, the initial burst of the drug from the silica surface, usually observed in other porous silica drug delivery systems, was avoided. The interaction between the β-cyclodextrin molecules and grafted amine functions were also studied as a function of pH. Finally, the cytotoxicity tests were performed using human glioma U87 MG cells

Oculocutaneous albinism type 2 (OCA2) with homozygous 2.7-kb deletion of the P gene and sickle cell disease in a Cameroonian family. Identification of a common TAG haplotype in the mutated P gene.

International audienceIn this study, we report on a Cameroonian family from the Ewondo ethnic group, presenting with three oculocutaneous albinism type 2 (OCA2) patients homozygous for the 2.7-kb deletion of the P gene. In one of these patients OCA2 was associated with sickle cell anaemia and in two with the sickle cell trait. We took this opportunity to determine single nucleotide polymorphism (SNP) haplotypes within the P gene in this family in comparison with a group of 53 OCA2 patients homozygous for the same mutation and with a matched unrelated full-coloured control group of 49 subjects, originating from seven different ethnic groups of Southern Cameroon including Ewondo. A combination of five exonic and intronic SNPs in the OCA2 gene was genotyped by sequencing PCR products. We found 3 different haplotypes (TAGCT, TAGTT and TAGCC with frequencies of 0.66, 0.28 and 0.06, respectively) associated with the mutation in the 53 OCA2 patients, while 11 different haplotypes were observed in the control group. These observations suggest that the mutation appeared on the relatively frequent haplotype TAGCT, and that the two other haplotypes are derived from two independent recombination events. These haplotypic data, associated with a value of 1/15,000 for the prevalence of the 2.7-kb mutation, a present effective population size of 10,000,000 for Cameroon and a recombination rate of 0.0031, allowed us to estimate that this mutation originated 4,100-5,645 years ago