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1.
A Newman-Tancredi V Audinot C Chaput L Verrièle MJ Millan 《Canadian Metallurgical Quarterly》1997,282(1):181-191
Great progress has been made in the last 10 years in the understanding of the various types of viral hepatitis, and new viruses, concepts, therapies, preventive measures, and control strategies have been recognized. Even more agents, vaccines, and drugs will be discovered or developed in the future, and pediatricians increasingly will be expected to provide guidance to patients and to the community on the importance and use of these new tools. 相似文献
2.
Ahlem A Samira M Jean-Nicolas A Mohamed-Habib J Henri-Noël M Ali el H Leila T 《Microscopy research and technique》2012,75(4):448-451
The frequent use of some rare earths in the medical and industrial domains make us worry about their intracellular behavior into the body. Reason for which we have investigated the subcellular localization of one of these elements, the samarium, in the mammary gland of lactating female wistar rats using two very sensitive methods of observation and microanalysis, the transmission electron microscopy and the secondary ion mass spectrometry. The ultrastructural study showed the presence of electron dense deposits in the lactating mammary glandular epithelial cell lysosomes of the samarium-treated rats, but no loaded lysosomes were observed in those of control rats. The microanalytical study allowed both the identification of the chemical species present in those deposits as samarium isotopes ((152) Sm(+)) and the cartography of its distribution. Our results confirm the previous ones showing that lysosomes of the glandular epithelial cells are the site of the intracellular concentration of foreign elements such as gallium. The intralysosomal deposits observed in the mammary glandular cells of the samarium-treated rats are similar in their form and density to those observed with the same element in other varieties of cells, such as liver, bone marrow, and spleen cells. Our ultrastructural and microanalytical results and those obtained in previous studies allow deducing that the intralysosomal deposits are very probably composed of an insoluble samarium phosphate salt. 相似文献
3.
Gregory L. Olsen Adonis Lupulescu Jean-Nicolas Dumez Lyndon Emsley Lucio Frydman 《Israel journal of chemistry》2014,54(1-2):154-162
Line narrowing has been traditionally achieved in solid-state 1H NMR spectroscopy by applying pulse sequences that combine multiple-pulse operations with magic-angle spinning (MAS), to effectively average out the dipole dipole homonuclear Hamiltonian. The present study explores a new alternative that departs from the usual concept of directly acting on the strongly coupled spins with radiofrequency pulses; instead, we seek to achieve a net homonuclear dipolar decoupling in solids by exploring the reintroduction of MAS-averaged heteronuclear dipolar couplings between the 1H nuclei and directly bonded 13C or 15N nuclei. This recoupling anti-recoupling (RaR) scheme thus relies on the recoupling of the dipolar interaction with heteronuclear spins, which, under fast MAS, will exceed the strength and will not commute with the homonuclear 1H 1H coupling one is intending to average out. Subsequent removal (“antiRecoupling”) of these heteronuclear interactions can lead to narrowed 1H resonances, without ever pulsing on the aforementioned channel. The line-narrowing properties of RaR are illustrated with numerical simulations and with experiments on model organic solids. 相似文献
4.
Maghraoui S Ayadi A Audinot JN Ben Ammar A Jaafoura MH El Hili A Migeon HN Tekaya L 《Microscopy research and technique》2012,75(2):182-188
The subcellular behavior of aluminum and indium, used in medical and industrial fields, was studied in the gastric mucosa and the liver after their intragastric administration to rats, using, two of the most sensitive methods of observation and microanalysis, the transmission electron microscopy, and the secondary ion mass spectrometry. The ultrastructural study showed the presence of electron dense deposits, in the lysosomes of parietal and principal gastric mucosa cells but no loaded lysosomes were observed in the different studied hepatic territories. The microanalytical study allowed the identification of the chemical species present in those deposits as aluminum or indium isotopes and the cartography of their distribution. No modification was observed in control rats tissues. In comparison to previous studies describing the mechanism of aluminum concentration in the gastric mucosa and showing that this element was concentrated in the lysosomes of fundic and antral human gastric mucosa, our study provided additional informations about the types of cells involved in the phenomenon of concentration of aluminum and indium, which are the parietal and the principal cells of the gastric mucosa. Our study demonstrated that these cells have the ability to concentrate selectively aluminum and indium in their lysosomes, as a defensive reaction against intoxication by foreign elements. 相似文献
5.
Dr. Morgan Le Naour Dr. Veronique Leclerc Dr. Amaury Farce Dr. Daniel‐Henri Caignard Dr. Nathalie Hennuyer Prof. Bart Staels Dr. Valérie Audinot‐Bouchez Dr. Jean‐Albert Boutin Dr. Michel Lonchampt Dr. Catherine Dacquet Prof. Alain Ktorza Prof. Pascal Berthelot Dr. Nicolas Lebegue 《ChemMedChem》2012,7(12):2179-2193
Compounds that simultaneously activate peroxisome proliferator‐activated receptor (PPAR) subtypes α and γ have the potential to effectively treat dyslipidemia and type 2 diabetes (T2D) in a single pharmaceutically active molecule. The frequently observed side effects of selective PPARγ agonists, such as edema and weight gain, were expected to be overcome by using additive PPARα activity, leading to dual PPARα/γ agonists with balanced activity for both subtypes. Herein we report the discovery, synthesis, and optimization of a new series of α‐ethoxyphenylpropionic acid bearing 5‐ or 6‐substituted indoles. The incorporation of oxime ethers on the carbonyl portion of the benzoyl group can bring the PPARα/γ potency ratio equal to or slightly greater than one, as is the case for compounds 20 c and 21 a . Compound 20 c shows high efficacy in an ob/ob mouse model of T2D and dyslipidemia, similar to that of rosiglitazone and tesaglitazar, but with a significant increase in body weight gain. In contrast, compound 21 a , less potent as a dual PPARα/γ activator than 20 c , showed an interesting pharmacological profile, as it elicits a decrease in body weight relative to reference compounds. 相似文献
6.
Sternitzke V Kaegi R Audinot JN Lewin E Hering JG Johnson CA 《Environmental science & technology》2012,46(2):802-809
Hydroxyapatite (Ca(10)(PO(4))(6)(OH)(2), HAP), both as a synthetic material and as a constituent of bone char, can serve as an effective and relatively inexpensive filter material for fluoride (F(-)) removal from drinking water in low-income countries. Fluoride uptake on HAP can occur through different mechanisms, which are, in principle, influenced by solution composition. Suspensions of HAP (2 g L(-1)) were equilibrated under controlled pH conditions (pH 6.5, 7.3, 9.5) at 25 °C for 28 d after the addition of different F(-) concentrations (0.5-7.0 mM). The reacted HAP solids were examined with Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Photoelectron Spectroscopy (XPS), and Nano Secondary Ion Mass Spectroscopy (NanoSIMS). Fluoride uptake on HAP was dependent on pH, with the highest capacity at pH 6.5; the lowest uptake was found at pH 9.5. Under all experimental conditions, the thermodynamically stable mineral phase was fluorapatite, (Ca(10)(PO(4))(6)F(2), FAP). Fluoride uptake capacity was quantified on the basis of FTIR and XPS analysis, which was consistent with F(-) uptake from solution. The results of XPS and NanoSIMS analyses indicate that a fluoridated surface layer with a thickness of several nanometers is formed on nanosized HAP. 相似文献
7.
Today's structural biology techniques require averaging over millions of molecules to obtain detailed structural information. Derivation of the molecular structure from a scattering experiment with just one single 3D-molecule imposes major challenges. Coherent and damage-free radiation is needed to ensure sufficient elastic scattering events before destroying the molecule and a means to solve the phase problem is wanted. We have devised such a scheme using coherent low-energy electrons shaped into a collimated beam by an electrostatic microlens. Initial experiments using a carbon nanotube sample demonstrate the feasibility of coherent low-energy electron diffraction on an individual nanometer-sized object. 相似文献
8.
MJ Millan A Newman-Tancredi M Brocco A Gobert F Lejeune V Audinot JM Rivet R Schreiber A Dekeyne M Spedding JP Nicolas JL Peglion 《Canadian Metallurgical Quarterly》1998,287(1):167-186
The novel benzoindane S 18126 possessed > 100-fold higher affinity at cloned, human (h) D4 (Ki = 2.4 nM) vs. hD2 (738 nM), hD3 (2840 nM), hD1 (> 3000 nM) and hD5 (> 3000 nM) receptors and about 50 other sites, except sigma1 receptors (1.6 nM). L 745,870 similarly showed selectivity for hD4 (2.5 nM) vs. hD2 (905 nM) and hD3 (> 3000 nM) receptors. In contrast, raclopride displayed low affinity at hD4 (> 3000 nM) vs. hD2 (1.1 nM) and hD3 receptors (1.4 nM). Stimulation of [35S]-GTPgammaS binding at hD4 receptors by dopamine (DA) was blocked by S 18126 and L 745,870 with Kb values of 2.2 and 1.0 nM, respectively, whereas raclopride (> 1000 nM) was inactive. In contrast, raclopride inhibited stimulation of [35S]-GTPgammaS binding at hD2 sites by DA with a Kb of 1.4 nM, whereas S 18126 (> 1000 nM) and L 745,870 (> 1000 nM) were inactive. As concerns presynaptic dopaminergic receptors, raclopride (0.01-0.05 mg/kg s.c. ) markedly enhanced DA synthesis in mesocortical, mesolimbic and nigrostriatal dopaminergic pathways. In contrast, even high doses (2. 5-40.0 mg/kg s.c.) of S 18126 and L 745,870 were only weakly active. Similarly, raclopride (0.016 mg/kg i.v.) abolished inhibition of the firing rate of ventrotegmental dopaminergic neurons by apomorphine, whereas even high doses (0.5 mg/kg i.v.) of S 18126 and L 745,870 were only weakly active. As regards postsynaptic dopaminergic receptors, raclopride potently (0.01-0.3 mg/kg s.c.) reduced rotation elicited by quinpirole in rats with unilateral lesions of the substantia nigra, antagonized induction of hypothermia by PD 128, 907, blocked amphetamine-induced hyperlocomotion and was effective in six further models of potential antipsychotic activity. In contrast, S 18126 and L 745,870 were only weakly active in these models (5.0-> 40.0 mg/kg s.c.). In six models of extrapyramidal and motor symptoms, such as induction of catalepsy, raclopride was likewise potently active (0.01-2.0 mg/kg s.c.) whereas S 18126 and L 745,870 were only weakly active (10.0-80.0 mg/kg s.c.). In freely moving rats, raclopride (0.16 mg/kg s.c.) increased levels of DA by + 55% in dialysates of the frontal cortex. However, it also increased levels of DA in the accumbens and striatum by 70% and 75%, respectively. In contrast to raclopride, at a dose of 0.16 mg/kg s.c. , neither S 18126 nor L 745,870 modified frontal cortex levels of DA. However, at a high dose (40.0 mg/kg s.c.), S 18126 increased dialysate levels of DA (+ 85%) and noradrenaline (+ 100%), but not serotonin (+ 10%), in frontal cortex without affecting DA levels in accumbens (+ 10%) and striatum (+ 10%). In conclusion, S 18126 and L 745,870 behave as potent and selective antagonists of cloned, hD4 vs. other dopaminergic receptor types in vitro. However, their in vivo effects at high doses probably reflect residual antagonist actions at D2 (or D3) receptors. Selective blockade of D4 receptors was thus associated neither with a modification of dopaminergic transmission nor with antipsychotic (antiproductive) or extrapyramidal properties. The functional effects of selective D4 receptor blockade remain to be established. 相似文献
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10.
MJ Millan A Gobert A Newman-Tancredi V Audinot F Lejeune JM Rivet D Cussac JP Nicolas O Muller G Lavielle 《Canadian Metallurgical Quarterly》1998,286(3):1341-1355
S 16924 showed a pattern of interaction at multiple (>20) native, rodent and cloned, human (h) monoaminergic receptors similar to that of clozapine and different to that of haloperidol. Notably, like clozapine, the affinity of S 16924 for hD2 and hD3 receptors was modest, and it showed 5-fold higher affinity for hD4 receptors. At each of these sites, using a [35S]GTPgammaS binding procedure, S 16924, clozapine and haloperidol behaved as antagonists. In distinction to haloperidol, S 16924 shared the marked affinity of clozapine for h5-HT2A and h5-HT2C receptors. However, an important difference to clozapine (and haloperidol) was the high affinity of S 16924 for h5-HT1A receptors. At these sites, using a [35S]GTPgammaS binding model, both S 16924 and clozapine behaved as partial agonists, whereas haloperidol was inactive. In vivo, the agonist properties of S 16924 at 5-HT1A autoreceptors were revealed by its ability to potently inhibit the firing of raphe-localized serotoninergic neurones, an action reversed by the selective 5-HT1A receptor antagonist, WAY 100,635. In contrast, clozapine and haloperidol only weakly inhibited raphe firing, and their actions were resistant to WAY 100,635. Similarly, S 16924 more potently inhibited striatal turnover of 5-HT than either clozapine or haloperidol. Reflecting its modest affinity for D2 (and D3) autoreceptors, S 16924 only weakly blocked the inhibitory influence of the dopaminergic agonist, apomorphine, upon the firing rate of ventrotegmental area-localized dopaminergic neurones. Further, S 16924 only weakly increased striatal, mesolimbic and mesocortical turnover of dopamine (DA). Clozapine was, similarly, weakly active in these models, whereas haloperidol, in line with its higher affinity at D2 (and D3) receptors, was potently active. In the frontal cortex (FCX) of freely moving rats, S 16924 dose-dependently reduced dialysate levels of 5-HT, whereas those of DA and NAD were dose-dependently increased in the same samples. In contrast, although S 16924 also suppressed 5-HT levels in the striatum and nucleus accumbens, DA levels therein were unaffected. Clozapine mimicked this selective increase in DA levels in the FCX as compared to striatum and accumbens. In contrast, haloperidol modestly increased DA levels in the FCX, striatum and accumbens to the same extent. In distinction to S 16924, clozapine and haloperidol exerted little influence upon 5-HT levels. Finally, the influence of S 16924 upon FCX levels of 5-HT, DA (and NAD) was attenuated by WAY 100,635. In conclusion, S 16924 possesses a profile of interaction at multiple monoaminergic receptors comparable to that of clozapine and distinct to that of haloperidol. In addition, S 16924 is a potent, partial agonist at 5-HT1A receptors. Correspondingly, acute administration of S 16924 decreases cerebral serotoninergic transmission and selectively reinforces frontocortical as compared to subcortical dopaminergic transmission. In line with these actions, S 16924 shows a distinctive profile of activity in functional (behavioral) models of potential antipsychotic activity (companion paper). 相似文献