Stability of the thrombin-thrombomodulin complex on the surface of endothelial cells from human saphenous vein or from the cell line EA.hy 926

Protein C activation by alpha-thrombin on the surface of endothelial cells depends on an essential membrane-glycoprotein cofactor, thrombomodulin. In the present study we have monitored the activity of thrombin-thrombomodulin complexes on human saphenous-vein endothelial cells (HSVEC) or on the endothelial cell line EA.hy 926. Cell monolayers were exposed for 5 min to 8.5 nM human alpha-thrombin and then washed to remove unbound thrombin. The cells were then incubated at 37 degrees C for 5-180 min. At the end of the respective incubation periods, purified human protein C (120 nM) was added in order to assay the activity of the thrombin-thrombomodulin complexes present on the cell surface. HSVEC pre-exposed to thrombin retained their full capacity to promote protein C activation up to 90 min after free thrombin was removed. This capacity then decreased slowly to reach 56% of control value after 180 min of incubation. Original activity was 3.8 +/- 0.9 pmol of activated protein C formed/min per ml per 10(6) cells (mean +/- S.E.M., n = 5). The capacity of protein C activation of EA.hy 926 cells remained constant for 120 min after free thrombin was removed, then decreased to 76% of control after 180 min. Original activity was 2.0 +/- 0.4 pmol of activated protein C formed/min per ml per 10(6) cells (mean +/- S.E.M., n = 3). Similar results were obtained with cells fixed with 3% paraformaldehyde. However, during the 5-180 min incubation period, non-fixed cells of both types were capable of significantly internalizing fluorescent acetylated low-density lipoprotein. In the experimental protocol used here, an eventual inhibition of thrombin internalization by protein C can be excluded, as protein C is only added at the end of the incubation period. We conclude that there is no evidence of rapid internalization of thrombin-thrombomodulin complexes on HSVEC or the EA.hy 926 cell line, as assessed by the ability of membrane-bound thrombin to activate protein C

Selective Vulnerability in Striosomes and in the Nigrostriatal Dopaminergic Pathway After Methamphetamine Administration: Early Loss of TH in Striosomes After Methamphetamine

Methamphetamine (METH), a commonly abused psychostimulant, causes dopamine neurotoxicity in humans, rodents, and nonhuman primates. This study examined the selective neuroanatomical pattern of dopaminergic neurotoxicity induced by METH in the mouse striatum. We examined the effect of METH on tyrosine hydroxylase (TH) and dopamine transporter (DAT) immunoreactivity in the different compartments of the striatum and in the nucleus accumbens. The levels of dopamine and its metabolites, 3,4-dihidroxyphenylacetic acid and homovanillic acid, as well as serotonin (5-HT) and its metabolite, 5-hydroxyindolacetic acid, were also quantified in the striatum. Mice were given three injections of METH (4 mg/kg, i.p.) at 3 h intervals and sacrificed 7 days later. This repeated METH injection induced a hyperthermic response and a decrease in striatal concentrations of dopamine and its metabolites without affecting 5-HT concentrations. In addition, the drug caused a reduction in TH- and DAT-immunoreactivity when compared to saline-treated animals. Interestingly, there was a significantly greater loss of TH- and DAT-immunoreactivity in striosomes than in the matrix. The predominant loss of dopaminergic terminals in the striosomes occurred along the rostrocaudal axis of the striatum. In contrast, METH did not decrease TH- or DAT-immunoreactivity in the nucleus accumbens. These results provide the first evidence that compartments of the mouse striatum, striosomes and matrix, and mesolimbic and nigrostriatal pathways have different vulnerability to METH. This pattern is similar to that observed with other neurotoxins such as MPTP, the most widely used model of Parkinson’s disease, in early Huntington’s disease and hypoxic/ischemic injury, suggesting that these conditions might share mechanisms of neurotoxicity

Simulation de microprocesseurs unilisant la technique de macro-generation

Pour simuler un microprocesseur sur un ordinateur central, la voie classique utilise une méthode interprétative en analysant, instruction par instruction, le code machine. En raison de sa lenteur et de son manque de souplesse, ce type de simulateur est mal adapté au développement complet d'algorithmes complexes de traitement du signal. Nous proposons une méthode qui permet d'accélérer par un facteur 1000 les temps de simulation. Cette- méthode, qui est basée sur la technique de la génération par macro-instructions, consiste à compiler directement le langage symbolique du microprocesseur et à le traduire en instructions de l'ordinateur hôte. Outre sa vitesse, ce type de simulateur permet d'accéder à toutes les facilités du système d'exploitation. On pourra, par exemple, utiliser des sous-programmes traduits par un compilateur. On simulera donc facilement en Fortran les opérations d'entrée-sortie, le monde extérieur, le mécanisme des interruptions, etc

Méthode d'initialisation rapide d'un annuleur d'écho et mise en oeuvre sur processeur de signal

Dans cet article, nous proposons une méthode basée sur l'utilisation d'une séquence de test qui permet d'évaluer le retard pur et les coefficients de l'annuleur d'écho à l'établissement d'une conversation téléphonique en moins de 200 ms. Puis, de manière à se garder d'une quelconque variation de charge de l'hybride en cours de conversation, les coefficients sont adaptés continuellement par la méthode du gradient. Après une analyse mathématique du problème et de la méthode utilisée, nous discutons sa mise en œuvre sur un processeur de signal et son insertion dans un réseau téléphonique. La méthode est efficace puisque le niveau relatif du signal d'écho par rapport au niveau du signal traversant le transformateur hybride est en pratique ramené à -40 dB dans le cas d'hybrides ayant une forte atténuation en retour (9 à 24dB), et à -30 dB dans le cas d'hybrides ayant une faible atténuation en retour (0 à 9dB)