A magnetic glassy phase in Fe(1+y)Se(x)Te(1-x) single crystals.

The evolution of magnetic order in Fe1+ySexTe1-x crystals as a function of Se content was investigated by means of ac/dc magnetometry and muon-spin spectroscopy. Experimental results and self-consistent density functional theory calculations both indicate that muons are implanted in vacant iron-excess sites, where they probe a local field mainly of dipolar origin, resulting from an antiferromagnetic (AFM) bicollinear arrangement of iron spins. This long-range AFM phase becomes progressively disordered with increasing Se content. At the same time all the tested samples manifest a marked glassy character that vanishes for high Se contents. The presence of local electronic/compositional inhomogeneities most likely favours the growth of clusters whose magnetic moment 'freezes' at low temperature. This glassy magnetic phase justifies both the coherent muon precession seen at short times in the asymmetry data, as well as the glassy behaviour evidenced by both dc and ac magnetometry.

First direct observation of the Van Hove singularity in the tunnelling spectra of cuprates.

In two-dimensional (2D) lattices, the electronic levels are unevenly spaced, and the density of states (DOS) displays a logarithmic divergence known as the Van Hove singularity (VHS). This is the case in particular for the layered cuprate superconductors. The scanning tunnelling microscope (STM) probes the DOS, and is therefore the ideal tool to observe the VHS. No STM study of cuprate superconductors has reported such an observation so far giving rise to a debate about the possibility of observing directly the normal state DOS in the tunnelling spectra. In this study, we show for the first time that the VHS is unambiguously observed in STM measurements performed on the cuprate Bi2Sr2CuO(6+δ) (Bi-2201). Beside closing the debate, our analysis proves the presence of the pseudogap in the overdoped side of the phase diagram of Bi-2201 and discredits the scenario of the pseudogap phase crossing the superconducting dome.

Imaging the essential role of spin fluctuations in high-T(c) superconductivity.

We have used scanning tunneling spectroscopy to investigate short-length electronic correlations in three-layer Bi2Sr2Ca2Cu3O(10+delta) (Bi-2223). We show that the superconducting gap and the energy Omega(dip), defined as the difference between the dip minimum and the gap, are both modulated in space following the lattice superstructure and are locally anticorrelated. Based on fits of our data to a microscopic strong-coupling model, we show that Omega(dip) is an accurate measure of the collective-mode energy in Bi-2223. We conclude that the collective mode responsible for the dip is a local excitation with a doping dependent energy and is most likely the (pi, pi) spin resonance.

DHA-enriched phospholipid diets modulate age-related alterations in rat hippocampus.

Our previous work on rat hippocampus showed that a loss of docosahexaenoic acid (DHA) occurs in the fatty acid composition of phosphatidylethanolamine (PE), plasmenylethanolamine (PmE) and phosphatidylserine (PS) with increasing age. The present study investigated whether a DHA-enriched phospholipid dietary supplement could restore DHA levels and cholinergic activity. Male rats were fed a balanced diet containing both linoleic and alpha-linolenic acids until the age of 2, 18 and 21 months. From 18 to 21 months, one subgroup received a diet supplemented with DHA-enriched phospholipids from egg yolk (E-PL), and another a diet with DHA-enriched phospholipids from pig brain (B-PL). Compared to the control diet, the E-PL diet restored the proportion of polyunsaturated fatty acids (PUFAs: 22:6n-3 and 20:4n-6) in PE and PmE, while enhancing spontaneous and evoked-acetylcholine (Ach) release. The B-PL diet had no effect on PUFAs, but increased basal extracellular levels of Ach in 21-month-old rats as compared to the age-matched control. Our results show that supplementation with DHA-enriched egg PL can enhance Ach release and correct PUFA composition.

Impairment of the neuronal dopamine transporter activity in MPP(+)-treated rat was not prevented by treatments with nitric oxide synthase or poly(ADP-ribose) polymerase inhibitors.

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes, via its metabolite MPP(+), damages of the nigrostriatal dopaminergic pathway, similar to those observed in Parkinson's disease. An intranigral injection of 10 microg MPP(+) in rat induced a decrease of about 30% of the neuronal dopamine transporter (DAT) activity 21 days after lesion. Based on the hypothesis that MPTP/MPP(+) neurotoxicity involves the nitric oxide (NO) production and/or an activation of poly(ADP-ribose) polymerase (PARP), we investigated the preventive effects of a treatment either with L-Name, a NO synthase (NOS) inhibitor or 3-aminobenzamide, a PARP inhibitor on the reduction of dopamine uptake induced by MPP(+). Rats received a daily injection i.p. of 50 mg/kg L-Name or 10 mg/kg 3-aminobenzamide 3 days before and during 21 days after the MPP(+) lesion. The results showed that inhibitors of NOS and PARP did not prevent the alteration of DAT activity induced by 10 microg MPP(+), indicating that NO and PARP were not involved in the biochemical cascade leading to the inhibition of rat DAT activity by MPP(+) in our experimental conditions.

Evidence against a major role of plasmalogens in the resistance of astrocytes in lactic acid-induced oxidative stress in vitro.

Astrocytes are known to play a key role in buffering extracellular pH variations and, in addition, they are particularly resistant to oxidative stress and subsequent lipid peroxidation. This great resistance may be ascribed to the presence of high concentrations of certain antioxidants, but another explanation may be the presence of a high quantity of plasmalogens, which are a special group of glycerophospholipids characterized by a vinyl ether bond instead of an ester bond in the sn-1 position of the glycerol backbone. Plasmalogens are sensitive to free radical attack and acidity, and numerous works have supported the hypothesis that they may be antioxidant molecules that protect cells from oxidative stress. The aim of this work was to investigate, on astrocytes in lactic acid-induced oxidative stress (pH 5.5), the behavior of phospholipids and, in particular, plasmalogens. Two main techniques, based on the susceptibility of the vinyl ether bond to hydrolysis, were employed in this study to measure plasmalogen levels. In both cases, the sn-1 vinyl ether linkage was cleaved using mercuric chloride, producing a lysophospholipid that was assessed by phosphorus measurement or using HCl treatment, producing a long-chain fatty aldehyde assayed by gas chromatography/mass spectrometry. On astrocytes in culture, only plasmenylethanolamine (PlmEtn) was evidenced, representing 40% of glycerophosphoethanolamine lipids. When astrocytes were incubated with lactic acid, no modification in the amount of PlmEtn was seen. Furthermore, free aldehydes and aldehydes corresponding to the quantity of intact plasmalogens were similar to those observed on controls. In addition, the constancy of two lipid peroxidation markers, thiobarbituric acid reactive substances and polyunsaturated fatty acids, was clear evidence of the resistance of these cells in lactic acid conditions. In conclusion, our results fail to demonstrate a major role of plasmalogens in the resistance of astrocytes in lactic acid-induced oxidative stress.

Age-related changes in ethanolamine glycerophospholipid fatty acid levels in rat frontal cortex and hippocampus.

Morphological and biochemical alterations are associated with a progressive age-related cognitive deficit. Plasmenylethanolamine, the major brain plasmalogen, may be modified during aging because of a possible antioxidant role and involvement in synaptic transmission. Two- and 18-month-old rats were used to study the effect of aging on the levels and acyl composition of plasmenylethanolamine (PmE), phosphatidylethanolamine (PE), and phosphatidylserine (PS) in the frontal cortex and hippocampus. Aging only reduced significantly the PE levels in the frontal cortex. In 18-month-old rats, the fatty acid composition of the three phospholipid classes studied showed an increase of monounsaturated fatty acid (18:1 n-9 and 20:1 n-9) and a decrease in polyunsaturated fatty acid (PUFAs), essentially docosahexaenoic acid (DHA). DHA was markedly decreased in hippocampus PE. DHA, but also arachidonic acid, were considerably lower in frontal cortex PmE. PS modifications were similar in both regions. Hippocampus and frontal cortex underwent specific age-induced modifications in PmE and PE acyl composition. This could produce different effects on the functional ability of these two structures involved in the processes of specific memorization.

Non-thermal effects of continuous 2.45 GHz microwaves on Fas-induced apoptosis in human Jurkat T-cell line.

Non-thermal effects of microwaves (MWs) are one of the main issues studied for revising standards. The effects of MW exposure on apoptosis at non-thermal level (48 h, 2.45 GHz, 5 mW/cm2) have been studied. Results obtained assess non-thermal MW effects on Fas, but neither on butyrate- nor on ceramide-induced apoptosis in human Jurkat T-cell line. These data show that MW interacts either with Fas pathway between receptor and caspase-3 activation or on membrane proteins (i.e. Fas receptor or neurosphyngomyelinase).

Origin of extracellular dopamine increase induced by lactic acid striatal perfusion monitored by microdialysis in the awake rat.

In previous studies we showed that a striatal lactic acid perfusion-induced lactacidosis produces a diphasic increase in extracellular dopamine (DA). In the present study, different pharmacological reagents were used to determine the origin of accumulated DA. Our data show that both DA accumulations were totally suppressed by tetrodotoxin and nicardipine, indicating a relationship with membrane depolarization and a Ca(2+)-dependent effect. The first DA peak was largely reduced by a specific inhibitor of DA uptake such as GBR-12935, and the second was totally suppressed by tyramine and reserpine and lowered and delayed by GBR-12935. These results compared to data in the literature suggest that the first increase in extracellular DA resulted mainly from a release of cytosolic DA by reversal of the DA transporter, while the second was mainly due to a release of vesicular DA by exocytosis. These data indicate that lactic acid perfusion helps clarify the mechanisms involved in this process and could be useful for the study of new treatments against the hyperactive dopaminergic reaction occuring during ischemia.

Lactic acid-induced increase of extracellular dopamine measured by microdialysis in rat striatum: evidence for glutamatergic and oxidative mechanisms.

Striatal lactacidosis was induced by direct lactic acid perfusion to obtain a local pH as close as possible to that observed in ischemia. In a previous study we showed that such lactacidosis produces a diphasic increase in extracellular dopamine (DA). The present work investigated whether DA accumulation is related to a glutamatergic mechanism and/or production of reactive oxygen species (ROS) in the striatum. Concentrations of extracellular DA, glutamate and hydroxyl radicals ((.)OH) were measured in the presence or absence of an N-methyl-D-aspartate (NMDA) receptor blocker (dizocilpine, MK-801) or an antioxidant (Trolox). Measurements were performed using high-performance liquid chromatography (HPLC) with electrochemical and fluorimetric detection on samples obtained by an in vivo microdialysis perfusion technique and stored at -80 degrees C. The increase in lactic acid-induced DA was entirely suppressed by MK-801 and Trolox. Lactacidosis also induced an increase in extracellular glutamate and (.)OH concentrations at the same time as the first DA accumulation, as well as another (.)OH accumulation which preceded and accompanied the second DA concentration peak. Glutamate release was totally inhibited by MK-801 or Trolox. The first peak of (.)OH production was completely suppressed by MK-801 and Trolox, but the second one was only suppressed by Trolox. These data showed that the increase in DA induced by lactic acid was related to glutamatergic excitotoxicity and ROS production, suggested that the kinetic of events was different for the two DA accumulations.

[Evaluation of six rapid tests for screening of cannabis in sweat, saliva and tears]. / Evaluation de six tests rapides pour le depistage du cannabis dans la sueur, la salive et les urines.

In order to demonstrate an intake of cannabis, there are a number of rapid tests, all of them being focused on urine. In this study, we evaluated the results of six tests when applied to sweat (DrugWipe), saliva and urine (Syva Rapidtest, Biomedix, Frontline, DrugWipe, Cortez Dako). Fifty regular users of cannabis and fifty persons who denied consuming it were studied. The results obtained with DrugWipe in sweat were compared with anamnesis data, whereas results obtained in saliva and urine were compared with those of gas chromatography--mass spectrometry. The results indicate that DrugWipe may be useful for screening cannabis in sweat when the intake took place less than two hours before. The results obtained in saliva showed that none of the tests studied are reliable to be used with this medium, because of the great number of false positive and false negative results. With urine, four tests (Syva Rapidtest, Biomedix, Cortez, Dako) led to very good results and may be recommended when an immediate presumptive test result is required.

[Tox-Didact:CD-ROM for toxicology education. Value in hospital toxicology]. / Tox-Didact: CD-ROM de formation en toxicologie. Intérêt en toxicologie hospitalière.

New teaching techniques should allow students more independence in their training, particularly in learning from problems and using clinical reasoning. We designed Tox-Didact, a modular multimedia educational software program, which is suitable for both students and professionals, regardless of their orientation (pharmacy or medicine) or level. Each module concerns four domains: diagnosis, biological monitoring, curative treatment and prevention. Tox-Didact is multidisciplinary, interactive, simple to use and reliable. Nineteen modules are now being prepared. In final form, Tox-Didact will cover all the acute and chronic pathologies of toxicology.

Origin of 4-hydroxynonenal incubation-induced inhibition of dopamine transporter and Na+/K+ adenosine triphosphate in rat striatal synaptosomes.

Previous experiments reported that an incubation of striatal synaptosomes with 4-hydroxynonenal (4-HNE) resulted in an inhibition of dopamine (DA) uptake and Na+/K+ adenosine triphosphate (ATPase) activity. The present work investigated whether theses inhibitions are related to a 4-HNE binding to the DA transporter (DAT) and the Na+/K+ ATPase. The number of specific [125I]-PE21 binding sites on the DAT was significantly reduced after incubation with 4-HNE. The Na+/K+ ATPase activity decrease induced by 4-HNE was partially reversed, in a dose-dependent manner, by veratridine, a pump stimulator agent. Our previous data (Morel, P., Tallineau, C., Pontcharraud, R., Piriou, A. and Huguet, F., Effects of 4-hydroxynonenal, a lipid peroxidation product, on dopamine transport and Na+/K+ ATPase in rat striatal synaptosomes. Neurochem. Int., 33 (1999) 531-540) combining with the data observed in this study suggest that changes in DA uptake in striatal synaptosomes are directly related to 4-HNE binding to the DAT, whereas the decrease in Na+/K+ ATPase activity resulted only partially from 4-HNE binding to the pump and is mainly secondary to membrane lipid disruption.

Synthesis and antioxidant activity of new tetraarylpyrroles.

The synthesis and in vitro antioxidant activity of 17 new tetraarylpyrroles are investigated by 2 tests highly documented in the literature: capability to prevent Fe(2+)-induced lipid peroxidation on microsomes, which is a membrane preparation rich in polyunsaturated fatty acids, and direct scavenging effect on a stable free radical, 1,l-diphenyl-2-picryl-hydrazyl (DPPH). For the Fe(2+)-induced microsomal lipid peroxidation system, the results show that molecules which possess 2-pyrazinyl or 2-pyridyl in the 3- and 4-positions on the pyrrole ring are the most efficient. Introduction of methoxy groups on the phenyl ring in the 2- and 5-positions increases the effects but the higher activity is obtained with 2-furyl or 2-thienyl. The only compounds which possess a direct scavenger effect on trapping the stable free radical DPPH are those which have 2-pyridyl in the 3- and 4-positions and 2-furyl or 2-thienyl in the 2- and 5-positions.

Membrane carbohydrate conjugates desialylation does not alter [3H]-dopamine uptake in rat striatal slices.

Incubation of rat striatal slices induced a large decrease (about 50%) of DA uptake and a slight desialylation of polysialogangliosides (GT1b, GD1b, GD1a) with an increase of monosialogangliosides (GM1). Moreover, a pretreatment of slices by exogenous added neuraminidase of Vibrio cholerae did not modify DA uptake, although the pattern of gangliosides was modified and there was considerable loss (about 45%) of sialic acid in gangliosides and glycoproteins. It was verified that neuraminidase activity occured in synaptic membrane. Thus, DA uptake was apparently not altered by desialylation of plasma membrane carbohydrate conjugates.

Extracellular dopamine and catabolites in rat striatum during lactic acid perfusion as determined by in vivo microdialysis.

Many experimental studies concerning hypoxia or ischemia have reported a decrease in intra/extracellular pH and massive dopamine (DA) release in the striatum. The present work investigated whether the increase in striatal extracellular DA is related to acidification or to lactate production. Striatal perfusion of lactic acid (pH 5.5) by microdialysis in conscious freely-moving rats induced an increase in extracellular concentrations of DA and catabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), as a probable result of acidification. Perfusion with sodium lactate (pH 7.4) failed to modify DA and catabolite release, whereas orthophosphoric acid produced the same effect as lactic acid. As lactic acidosis is known to induce a displacement of iron from its uptake sites, the possible role of this metal in response to acidosis was studied by perfusing ferrozine, an iron complexing agent, at the same time as lactic acid. The results showed that ferrous ions are involved in the process and suggested that oxygen free radicals play a role in the extracellular release of DA. Thus, lactic acid perfusion in rat striatum would appear to be a useful model for in vivo studies of the mechanisms responsible for increases in extracellular DA during hypoxia and ischemia.

Possible relationship between changes in [3H]DA uptake and autoxidation in rat striatal slices.

Many recent studies have suggested that oxidative damage is an important factor in several neurodegenerative disorders. Our investigations considered whether autoxidation of rat striatal slices modified dopamine uptake. Biochemical assays (TBARS, MDA-TBA complex, aldehydes, and fluorescent lipid-soluble products) and a [3H]DA uptake assay were performed on nonincubated striatal slices and on slices incubated for 150 min at 37 degreesC in Krebs-Ringer buffer without addition of free-radical generators. The results showed that spontaneous lipid peroxidation occured during incubation and that DA uptake kinetic was biphasic (high-affinity uptake1 and low-affinity uptake2) with a significant decrease of maximal velocity of uptake. Ascorbate, a known antioxidant, was used to determine whether a relationship existed between lipid peroxidation and reduced dopamine uptake. Addition of ascorbate (100 and 500 microM) in Krebs-Ringer buffer for 150 min at 37 degreesC failed to indicate whether decreased [3H]DA uptake resulted from lipid peroxidation. In fact, ascorbate acted as a prooxidant, only preventing decreased DA uptake2 at 100 microM. Trolox, another antioxidant, inhibited lipid peroxidation by about 95% with a concentration of 700 microM and protected only uptake1. With a concentration of 5000 microM, Trolox also protected uptake2. On the whole, these results indicate that spontaneous autoxidation in rat striatal slices was associated with a lipid peroxidation process that altered the DA uptake system.

Characterization of both dopamine uptake systems in rat striatal slices by specific pharmacological tools.

Previous results have shown that modifications of dopamine (DA) high-affinity uptake1 and those of DA low-affinity uptake2 in rat striatal slices were different after autoxidation of this model and in the presence of antioxidants. The aim of this study was to determine whether these two DA uptake systems correspond to two different dopamine transporters or rather to a single one. A lesion into the substantia nigra of animals by injection of 6-hydroxydopamine, a neurotoxic substance of nigrostriatal dopaminergic neurons led to the suppression of both DA uptake systems. These two DA uptake systems were not modified when animals were treated by reserpine or tetrabenazine, which inhibit the vesicular monoamine transporter. Moreover, they were sodium- and temperature-dependent. Experiments with specific inhibitors showed that 1-[2-(diphenylmethoxy) ethyl]-4-(3-phenylpropyl)-piperazine dihydrochloride (GBR-12935) and (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-tolyl ) nortropane chloride (PE2I), two selective DA uptake inhibitors, were significantly more potent than fluoxetine and nisoxetine (selective serotonin and norepinephrine uptake inhibitors respectively) in both DA uptake systems. However, the concentrations of these products inhibiting low-affinity uptake2 by 50% were much greater than those for high-affinity uptake1. Our data indicate that both DA uptake systems are neuronal, independent of the vesicular monoamine transporter, active and specific for dopamine. Our results suggest that high-affinity uptake1 and low-affinity uptake2 correspond to the same dopamine transporter, but would be situated at different levels in the striatal slice model. Uptake1 could take place at the periphery of the slice whereas uptake2 in the depth of the slice.

Effects of 4-hydroxynonenal, a lipid peroxidation product, on dopamine transport and Na+/K+ ATPase in rat striatal synaptosomes.

Incubation of rat striatal synaptosomes in ascorbic acid induced the production of thiobarbituric acid reactive substances, a marker of lipid peroxidation, and 4-hydroxynonenal (4-HNE), a lipid peroxidation aldehydic product. Incubations with 4-HNE, used at a range of concentrations comparable to those obtained during peroxidation, induced a simultaneous, dose-dependent decrease of dopamine (DA) uptake and Na+/K+ ATPase activity and a loss of sulfhydryl (SH) groups. Similar results were observed in a previous study when lipid peroxidation was induced after incubation of synaptosomes in ascorbic acid. Taken together, these data suggest that 4-HNE is an important mediator of oxidative stress and may alter DA uptake after binding to SH groups of the DA transporter and to Na+/K+ ATPase. These toxic events may contribute to the onset and progression of Parkinson's disease.