Impact of after-treatment devices and biofuels on diesel exhausts genotoxicity in A549 cells exposed at air-liquid interface.

Using an air-liquid interface (ALI) device in dynamic conditions, we evaluated the efficiency of fuel after-treatment strategies (diesel oxidation catalysis, DOC, and diesel particulate filter, DPF, devices) and the impact of 7% and 30% rapeseed methyl esters (RME) blending on oxidative stress and genotoxicity induced in A549 lung cells after 3h exposure to whole Diesel exhausts. Oxidative stress was studied using assays of ROS production, glutathione level, catalase and superoxide-dismutase (SOD) activities. No oxidative stress and no clear differences on cytotoxicity patterns between biodiesel and standard Diesel exhausts were found. A weak but significant genotoxicity (8-oxodGuo adducts) and, for standard Diesel only, a DNA damage response (DDR) as evidenced by ƔH2AX foci, remained after DOC+DPF flowing. All together, these data could contribute to the improvement of the after treatment strategies and to health risk assessment of current diesel exhausts.

Phthalocyanine based molecular spintronic devices.

Molecular spintronics is an effervescent field of research, which aims at combining spin physics and molecular nano-objects. In this article, we show that phthalocyanine molecules integrated in magnetic tunnel junctions (MTJs) can lead to magnetoresistance effects of different origins. We have investigated cobalt and manganese phthalocyanine molecule based magnetic tunnel junctions. CoPc MTJs exhibit both tunneling magnetoresistance (TMR) and tunneling anisotropic magnetoresistance (TAMR) effects of similar magnitude. However, for MnPc MTJs, a giant TAMR dominates with ratios up to ten thousands of percent. Strong features visible in the conductance suggest that spin-flip inelastic electron tunneling processes occur through the Mn atomic chain formed by the MnPc stacks. These results show that metallo-organic molecules could be used as a template to connect magnetic atomic chains or even a single magnetic atom in a solid-state device.

Probing electron-phonon excitations in molecular junctions by quantum interference.

Electron-phonon coupling is a fundamental inelastic interaction in condensed matter and in molecules. Here we probe phonon excitations using quantum interference in electron transport occurring in short chains of anthraquinone based molecular junctions. By studying the dependence of molecular junction's conductance as a function of bias voltage and temperature, we show that inelastic scattering of electrons by phonons can be detected as features in conductance resulting from quenching of quantum interference. Our results are in agreement with density functional theory calculations and are well described by a generic two-site model in the framework of non-equilibrium Green's functions formalism. The importance of the observed inelastic contribution to the current opens up new ways for exploring coherent electron transport through molecular devices.

[Vitamin D deficiency rickets complicating Dorfman-Chanarin syndrome]. / Rachitisme carentiel compliquant une maladie de Chanarin-Dorfman.

Vitamin D deficiency rickets remains a public health issue in many parts of the world. In France, this diagnosis has almost disappeared since 1992 with routine vitamin D supplementation for children. Therefore, it is more difficult for doctors to identify risk factors and early signs of this disease. In this article, we report a rickets diagnosis acquired by vitamin D deficiency in a child who presented with the onset of a genu valgum and difficulty walking at the age of 9½ years. This patient was a Comorian child followed up from his birth for Dorfman-Chanarin syndrome. Dorfman-Chanarin syndrome is a rare disease, with about 80 cases reported in the literature. It belongs to the group of neutral lipid storage diseases (NLSD) characterized especially on the skin by ichthyosis. This child presented risk factors for vitamin D deficiency (dark skin color, prolonged and exclusive breastfeeding, premature end of supplementation, and particularly severe ichthyosis) that should have alerted us to the risk of vitamin D deficiency and the need for supplementation. This case highlights the importance of vitamin D, especially if there are risk factors such as ichthyosis, and the need to remain watchful in monitoring all chronic diseases.

Comparative mutagenicity and genotoxicity of particles and aerosols emitted by the combustion of standard vs. rapeseed methyl ester supplemented bio-diesel fuels: impact of after treatment devices: oxidation catalyst and particulate filter.

Diesel exhausts are partly responsible for the deleterious effects on human health associated with urban pollution, including cardiovascular diseases, asthma, COPD, and possibly lung cancer. Particulate fraction has been incriminated and thus largely investigated for its genotoxic properties, based on exposure conditions that are, however, not relevant for human risk assessment. In this paper, original and more realistic protocols were used to investigate the hazards induced by exhausts emitted by the combustion of standard (DF0) vs. bio-diesel fuels (DF7 and DF30) and to assess the impact of exhaust treatment devices (DOC and DPF). Mutagenicity and genotoxicity were evaluated for (1) resuspended particles ("off line" exposure that takes into account the bioavailability of adsorbed chemicals) and for (2) the whole aerosols (particles+gas phase components) under continuous flow exposure ("on line" exposure). Native particles displayed mutagenic properties associated with nitroaromatic profiles (YG1041), whereas PAHs did not seem to be involved. After DOC treatment, the mutagenicity of particles was fully abolished. In contrast, the level of particle deposition was low under continuous flow exposure, and the observed mutagenicity in TA98 and TA102 was thus attributable to the gas phase. A bactericidal effect was also observed in TA102 after DOC treatment, and a weak but significant mutagenicity persisted after DPF treatment for bio-diesel fuels. No formation of bulky DNA-adducts was observed on A549 cells exposed to diesel exhaust, even in very drastic conditions (organic extracts corresponding to 500 µg equivalent particule/mL, 48 h exposure). Taken together, these data indicate that the exhausts issued from the bio-diesel fuels supplemented with rapseed methyl ester (RME), and generated by current diesel engines equipped with after treatment devices are less mutagenic than older ones. The residual mutagenicity is linked to the gas phase and could be due to pro-oxydants, mainly for RME-supplemented fuels.

Acute and long-term transcriptional responses in sulfur mustard-exposed SKH-1 hairless mouse skin.

Sulfur mustard (HD) ranks among the alkylating chemical warfare agents. Skin contact with HD produces an inflammatory response that evolves into separation at the epidermal-dermal junction conducting to blistering and epidermis necrosis. Up to now, current treatment strategies of HD burns have solely consisted in symptomatic management of skin damage. Therapeutic efficacy studies are still being conducted; classically using appropriate animal skin toxicity models. In order to substantiate the use of SKH-1 hairless mouse as an appropriate model for HD-induced skin lesions, we investigate the time-dependent quantitative gene expression of various selected transcripts associated to the dorsal skin exposure to HD saturated vapors. Using quantitative real time polymerase chain reaction (RT-qPCR), the expression of interleukins (IL-1ß and IL-6), tumor necrosis factor (TNF)-α, macrophage inflammatory proteins (MIP)-2α (also called Cxcl2) and MIP-1αR (also called Ccr1), matrix metalloproteases (MMP-9 and MMP-2), laminin γ2 monomer (Lamc2) and keratin (K)1 was determined up to 21 days after HD challenge in order to allow enough time for wound repair to begin. Specific transcript RT-qPCR analysis demonstrated that IL-6, IL-1ß, Ccr1, Cxcl2 mRNA levels increased as early as 6 h in HD-exposed skins and remained up-regulated over a 14-day period. Topical application of HD also significantly up-regulated MMP-9, TNF-α, and Lamc2 expression at specific time points. In contrast, MMP-2 mRNA levels remained unaffected by HD over the time-period considered, whereas that long-term study revealed that K1 mRNA level significantly increased only 21 days after HD challenge. Our study hereby provides first-hand evidence to substantiate a long period variation expression in the inflammatory cytokine, MMPs and structural components following cutaneous HD exposure in hairless mouse SKH-1. Our data credit the use of SKH-1 for investigating mechanisms of HD-induced skin toxicity and for the development of pharmacological countermeasures.

Stabilization of the active form(s) of human paraoxonase by human phosphate-binding protein.

While there is a consensus that human PON1 (paraoxonase-1) has a protective role, its primary biological function remains unclear. A protective role against poisoning by organophosphates [OPs (organophosphorus compounds)] drove earlier works. Clinical interest has recently focused on a protective role of PON1 against vascular diseases. PON1 resides mainly on HDL (high-density lipoprotein) particles, and converging recent works show that both its activities and stability dramatically depend on this versatile and dynamic molecular environment. The discovery that HPBP (human phosphate-binding protein) has a firm tendency to associate with PON1 has steered new directions for characterizing PON1 functional state(s). Storage stability studies provided evidence that HPBP is involved in maintaining physiologically active PON1 conformation(s). Thermal stability studies showed that human PON1 is remarkably thermostable and that its association with HPBP strongly contributes to slowing down the denaturation rate. A hybrid PON1, displaying mutations that stabilized recombinant enzyme expressed in Escherichia coli, was shown to be more thermostable than natural human PON1. Predictably, its stability was unaffected by the presence of HPBP. Synergistic efforts on characterizing natural PON1 and rPON1 (recombinant PON1) provide information for the design of future stable mutants of PON1-based bioscavengers to be used as safe and effective countermeasures to challenge OPs. Maintaining a stable environment for such administrable human rPON1 should, at least, preserve the anti-atherogenic activity of the enzyme.

[Long-term outcome of mitral valve repair of dystrophic mitral regurgitation]. / Evaluation à long terme de la chirurgie réparatrice dans l'insuffisance mitrale dystrophique.

Between January 1984 and December 1994, 130 patients underwent mitral valvuloplasty for pure dystrophic mitral regurgitation. There were 94 men and 36 women with a mean age of 61 +/- 9 years: 52 patients were in atrial fibrillation; 91% of patients were in NYHA Classes III or IV. At preoperative echocardiography, the regurgitation was assessed as Grade III or IV and classified using the Carpentier classification according to type I (dilatation of the annulus) or II (mitral valve prolapse); 95% of patients had isolated prolapse of the posterior leaflet, 3% had isolated prolapse of the anterior leaflet and 2% had prolapse of the two leaflets. After valvuloplasty, a prosthetic ring was implanted in 124 patients (95%). The early mortality was 3%; 5.3% of patients had early complications. All patients underwent control transthoracic echocardiography in the first postoperative week. They were reviewed with a second transthoracic echocardiography after a mean follow-up of 5 +/- 0.3 years and a cumulative follow-up of 657 years-patients. At the immediate postoperative echocardiography, 24 minimal residual regurgitations were observed; at long-term, 20 new mitral regurgitations developed, all mild without any clinical symptoms and 98% of patients were in the NYHA Classes I or II. At 10 years, the actuarial survival was 73 +/- 16%; absence of thromboembolic complications 95 +/- 3%, absence of reoperation 95 +/- 5%. This study confirms the efficacy of mitral valvuloplasty and the postoperative stability of repaired valvular lesions. These results suggest that the operative indications should be considered at an earlier stage.

[Value of coronary reperfusion in cases of very low cardiac output following coronary artery bypass grafts]. / Intérêt de la reperfusion coronaire dans les bas débits cardiaques graves après pontage coronaire.

From January 1986 to December 1988, 244 patients had a coronary artery revascularization at St Joseph Hospital. Four patients (1.8%) died in post operative time (less than 30 days). None died directly from cardiogenic shock. Five patients had a severe low cardiac output (2 h to 48 h post-op) and needed cardiac resuscitation. These patients were immediately taken to the operating room. The coronary bypasses were explored (2 technical errors corrected), the metabolic disorders were treated and a coronary reperfusion was done with the Buckberg's technique. All the patients could be weaned from cardiopulmonary bypass, two with intra aortic balloon pumping. One patient died of digestive complication the 10th postoperative day. The four other patients survived and are in good clinical condition. The severe low cardiac output after coronary revascularization can be reversible with resuscitation in operating room, short assistance, and coronary reperfusion.

[State of nitrite in meat products]. / Etudes sur l'état du nitrite dans les produits de viandes.

The authors search the form under which nitrite is in cured products. Nitrate formation found by official methods is not confirmed by qualitative characterization. The calculations, according to the chemical equations, show the total breakdown of nitrite in nitroge oxide: NO, bound by many substances which are in meats. The distillation experiments confirm the calculations, the characteristic photometric spectra get in sulfitic medium and the modified Zambelli's reaction. These results lead to estimate that both technologic and toxicologic actions impute to nitrite is dominated by the idea of NO more or less bound, according to the medium composition.