Une protection contre les lesions dues a une ischmie-reperfusion peut etre induite par le diazoxi... more Une protection contre les lesions dues a une ischmie-reperfusion peut etre induite par le diazoxide, un ouvreur de canaux potassiques ATP-dependants (Katp). Le diazoxide est aussi connu pour inhiber la succinate deshydrogenase (SDH), enzyme de la chaine respiratoire et du cycle de Krebs. Pour mieux comprendre les mecanismes en jeu, nous avons caracterise la lignee cellulaire d'origine cardiaque HL-1-NB, adaptee a l'utilisation de techniques optiques, pour suivre en temps reel plusieurs parametres cellulaires. Sur ce modele nous avons montre que le diazoxide n'induit pas l'ouverture des canaux KATP, ni sarcolemmaux, ni mitochondriaux, dans des conditions qui induisent pourtant une protection. Nos resultats sont en faveur d'un role cle de l'inhibition de la SDH dans l'induction de la protection. Ils suggerent par ailleurs que le diazoxide pourrait avoir, par une action sur les canaux KATP sarcolemmaux, independamment de leur ouverture, un effet metabolique ...
Analytical and quantitative cytology and histology, 2009
OBJECTIVE To evaluate the capture of nanoparticles (quantum dots [QDs], fluorospheres) by nonbeat... more OBJECTIVE To evaluate the capture of nanoparticles (quantum dots [QDs], fluorospheres) by nonbeating mouse cardiac cells (HL1-NB) cultured without or with 7-ketocholesterol (7KC) found at an increased level in the plasma of atherosclerotic patients and to simultaneously analyze their cytotoxic, proinflammatory and oxidative properties. STUDY DESIGN Flow cytometry (FCM), confocal laser scanning microscopy and subsequent factor analysis image processing were used to characterize the uptake of nanoparticles and to define their cytotoxicity, evaluated by enhanced permeability to SYTOX Green, release of lactate dehydrogenase (LDH) and morphologic nuclear changes determined with Hoechst 33342. Proinflammatory effects were estimated by enzyme linked immunoassay to quantify IL-8 and MCP-1 secretion. The overproduction of reactive oxygen species (ROS) was determined by FCM with hydroethidine. RESULTS Whereas the nanoparticles had no cytotoxic or inflammatory effects, they could stimulate ROS...
Écrit par et pour des francophones, cet ouvrage vous invite à découvrir la langue turque de façon... more Écrit par et pour des francophones, cet ouvrage vous invite à découvrir la langue turque de façon ludique et efficace, depuis la prononciation de l'alphabet jusqu'à la construction de phrases complexes. Laissez-vous guider par le titre de chacune des 45 leçons pour comprendre la grammaire et la conjugaison. Mettez en pratique immédiatement vos connaissances dans les exercices correspondants.
Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology, 2009
To evaluate the capture of nanoparticles (quantum dots [QDs], fluorospheres) by nonbeating mouse ... more To evaluate the capture of nanoparticles (quantum dots [QDs], fluorospheres) by nonbeating mouse cardiac cells (HL1-NB) cultured without or with 7-ketocholesterol (7KC) found at an increased level in the plasma of atherosclerotic patients and to simultaneously analyze their cytotoxic, proinflammatory and oxidative properties. Flow cytometry (FCM), confocal laser scanning microscopy and subsequent factor analysis image processing were used to characterize the uptake of nanoparticles and to define their cytotoxicity, evaluated by enhanced permeability to SYTOX Green, release of lactate dehydrogenase (LDH) and morphologic nuclear changes determined with Hoechst 33342. Proinflammatory effects were estimated by enzyme linked immunoassay to quantify IL-8 and MCP-1 secretion. The overproduction of reactive oxygen species (ROS) was determined by FCM with hydroethidine. Whereas the nanoparticles had no cytotoxic or inflammatory effects, they could stimulate ROS production. QDs were not incor...
Canadian Journal of Physiology and Pharmacology, 2009
Comparative analysis of the bioenergetic parameters of adult rat cardiomyocytes (CM) and HL-1 cel... more Comparative analysis of the bioenergetic parameters of adult rat cardiomyocytes (CM) and HL-1 cells with very different structure but similar cardiac phenotype was carried out with the aim of revealing the importance of the cell structure for regulation of its energy fluxes. Confocal microscopic analysis showed very different mitochondrial arrangement in these cells. The cytochrome content per milligram of cell protein was decreased in HL-1 cells by a factor of 7 compared with CM. In parallel, the respiratory chain complex activities were decreased by 4–8 times in the HL-1 cells. On the contrary, the activities of glycolytic enzymes, hexokinase (HK), and pyruvate kinase (PK) were increased in HL-1 cells, and these cells effectively transformed glucose into lactate. At the same time, the creatine kinase (CK) activity was significantly decreased in HL-1 cells. In conclusion, the results of this study comply with the assumption that in contrast to CM in which oxidative phosphorylation ...
Le developpement de capacites de communication et de reflexivite dans le cadre de la relation med... more Le developpement de capacites de communication et de reflexivite dans le cadre de la relation medecin-patient fait partie des objectifs pedagogiques du deuxieme cycle des etudes medicales en France. La reforme du Certificat de Competence Clinique (arrete du 8 avril 2013) en demande l’evaluation sous la forme d’une mise en situation clinique aupres d’un patient ou d’une epreuve de simulation. Dans ce contexte nous avons mis en place des jeux de role de simulation relationnelle et nous sommes interesses aux conditions dans lesquelles ils permettent de developper les competences relationnelles. Une etude observationnelle a ete menee dans le cadre de l’enseignement de Sciences Humaines et Sociales aupres des 360 etudiants en troisieme annee de medecine de la Faculte Lyon Est en septembre 2015. Deux seances de jeux de role de 2h avec 4 synopsis de consultations de medecine generale chacune ont ete concues en tenant compte des recommandations de la Haute Autorite de Sante (HAS, 2012). Un ...
Peripheral venous catheter insertion is a procedural skill that every medical student should mast... more Peripheral venous catheter insertion is a procedural skill that every medical student should master. Training is often limited to a small number of students and is poorly evaluated. The objective of this study was to evaluate the performance of peer-assisted learning in comparison to instructor-led teaching for peripheral venous catheter insertion training. Students were randomized to the control group attending a traditional instructor-led training session (slideshow and demonstration by an anesthetist instructor, followed by training on a procedural simulator) or to the test group attending a peer-assisted training session (slideshow and demonstration video-recorded by the same instructor, followed by training on a procedural simulator). The primary endpoint was the performance of peripheral venous catheter insertion, assessed on procedural simulator one week later by blinded experts using a standardized 20-item grid. Students self-evaluated their confidence levels using a numeric 10-point scale. Eighty-six students were included, 73 of whom attended the assessment session. The median performance score was 12/20 [8-15] in the instructor-led teaching group versus 13/20 [11-15] in the peer-assisted learning group (P=0.430). Confidence levels improved significantly after the assessment session and were significantly higher in the peer-assisted learning group (7.6/10 [7.0-8.0] versus 7.0/10 [5.0-8.0], P=0.026). Peer-assisted learning is effective for peripheral venous catheter insertion training and can be as effective as instructor-led teaching. Given the large number of students to train, this finding is important for optimizing the cost-effectiveness of peripheral venous catheter insertion training.
Basé sur l'association de mots (noms, adjectifs, verbes), l'ouvrage se divise en quatre p... more Basé sur l'association de mots (noms, adjectifs, verbes), l'ouvrage se divise en quatre parties : la première consacrée aux règles générales ; la deuxième consacrée aux noms et aux adjectifs ; la troisième consacrée aux verbes ; la quatrième consacrée aux expressions idiomatiques. Au fil des pages, le lecteur maîtrisera les clés indispensables pour parler et écrire un turc courant et fluide.
Basé sur l'association de mots (noms, adjectifs, verbes), l'ouvrage se divise en quatre p... more Basé sur l'association de mots (noms, adjectifs, verbes), l'ouvrage se divise en quatre parties : la première consacrée aux règles générales ; la deuxième consacrée aux noms et aux adjectifs ; la troisième consacrée aux verbes ; la quatrième consacrée aux expressions idiomatiques. Au fil des pages, le lecteur maîtrisera les clés indispensables pour parler et écrire un turc courant et fluide.
Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology, 2009
To evaluate the capture of nanoparticles (quantum dots [QDs], fluorospheres) by nonbeating mouse ... more To evaluate the capture of nanoparticles (quantum dots [QDs], fluorospheres) by nonbeating mouse cardiac cells (HL1-NB) cultured without or with 7-ketocholesterol (7KC) found at an increased level in the plasma of atherosclerotic patients and to simultaneously analyze their cytotoxic, proinflammatory and oxidative properties. Flow cytometry (FCM), confocal laser scanning microscopy and subsequent factor analysis image processing were used to characterize the uptake of nanoparticles and to define their cytotoxicity, evaluated by enhanced permeability to SYTOX Green, release of lactate dehydrogenase (LDH) and morphologic nuclear changes determined with Hoechst 33342. Proinflammatory effects were estimated by enzyme linked immunoassay to quantify IL-8 and MCP-1 secretion. The overproduction of reactive oxygen species (ROS) was determined by FCM with hydroethidine. Whereas the nanoparticles had no cytotoxic or inflammatory effects, they could stimulate ROS production. QDs were not incor...
The present study discusses the role of structural organization of cardiac cells in determining t... more The present study discusses the role of structural organization of cardiac cells in determining the mechanisms of regulation of oxidative phosphorylation and interaction between mitochondria and ATPases. In permeabilized adult cardiomyocytes, the apparent K(m) (Michaelis-Menten constant) for ADP in the regulation of respiration is far higher than in mitochondria isolated from the myocardium. Respiration of mitochondria in permeabilized cardiomyocytes is effectively activated by endogenous ADP produced by ATPases from exogenous ATP, and the activation of respiration is associated with a decrease in the apparent K(m) for ATP in the regulation of ATPase activity compared with this parameter in the absence of oxidative phosphorylation. It has also been shown that a large fraction of the endogenous ADP stimulating respiration remains inaccessible for the exogenous ADP trapping system, consisting of pyruvate kinase and phosphoenolpyruvate, unless the mitochondrial structures are modified ...
HL-1, the first cell line with a cardiac phenotype for biological experiments, displays spontaneo... more HL-1, the first cell line with a cardiac phenotype for biological experiments, displays spontaneous electrophysiological and mechanical regular activity, and cyclic calcium movements. We isolated a derived line, devoid of transient movements, for confocal microscopy experiments. These cells do express cardiac proteins: connexin 43, the cardiac isoform of dihydropyridine receptors, desmin, and developmental myosin but have no sarcomeric arrangement. They still possess the electrophysiological characteristics and ionic currents of cardiac cells, among them the cardiac potassium current IKr. We also found diazoxide and glibenclamide sensitive potassium channels with properties similar to IK(ATP) in adult cardiac myocytes. The pacemaker current I(f) was not observed, in agreement with the cells showing excitability but lacking in pacemaker activity. The absence of movement is an advantage for studies which include changes of media in order to follow morphological changes under continuou...
Progress in Biophysics and Molecular Biology, 2006
HL-1, the first cell line with a cardiac phenotype for biological experiments, displays spontaneo... more HL-1, the first cell line with a cardiac phenotype for biological experiments, displays spontaneous electrophysiological and mechanical regular activity, and cyclic calcium movements. We isolated a derived line, devoid of transient movements, for confocal microscopy experiments. These cells do express cardiac proteins: connexin 43, the cardiac isoform of dihydropyridine receptors, desmin, and developmental myosin but have no sarcomeric arrangement. They still possess the electrophysiological characteristics and ionic currents of cardiac cells, among them the cardiac potassium current IKr. We also found diazoxide and glibenclamide sensitive potassium channels with properties similar to IK(ATP) in adult cardiac myocytes. The pacemaker current I(f) was not observed, in agreement with the cells showing excitability but lacking in pacemaker activity. The absence of movement is an advantage for studies which include changes of media in order to follow morphological changes under continuous perfusion. We observed however a basal spontaneous movement of mitochondria and we developed a method to quantify its amplitude using confocal microscopy. No mitochondrial depolarization could be detected when the membrane potential was measured by using very low light photomultiplier and confocal fluorescence imaging under the K(ATP) channel opener diazoxide. Thus cardiac pharmacological preconditioning by K(ATP) channel openers might involve other routes than mitochondrial K channels targeting.
Une protection contre les lesions dues a une ischmie-reperfusion peut etre induite par le diazoxi... more Une protection contre les lesions dues a une ischmie-reperfusion peut etre induite par le diazoxide, un ouvreur de canaux potassiques ATP-dependants (Katp). Le diazoxide est aussi connu pour inhiber la succinate deshydrogenase (SDH), enzyme de la chaine respiratoire et du cycle de Krebs. Pour mieux comprendre les mecanismes en jeu, nous avons caracterise la lignee cellulaire d'origine cardiaque HL-1-NB, adaptee a l'utilisation de techniques optiques, pour suivre en temps reel plusieurs parametres cellulaires. Sur ce modele nous avons montre que le diazoxide n'induit pas l'ouverture des canaux KATP, ni sarcolemmaux, ni mitochondriaux, dans des conditions qui induisent pourtant une protection. Nos resultats sont en faveur d'un role cle de l'inhibition de la SDH dans l'induction de la protection. Ils suggerent par ailleurs que le diazoxide pourrait avoir, par une action sur les canaux KATP sarcolemmaux, independamment de leur ouverture, un effet metabolique ...
Analytical and quantitative cytology and histology, 2009
OBJECTIVE To evaluate the capture of nanoparticles (quantum dots [QDs], fluorospheres) by nonbeat... more OBJECTIVE To evaluate the capture of nanoparticles (quantum dots [QDs], fluorospheres) by nonbeating mouse cardiac cells (HL1-NB) cultured without or with 7-ketocholesterol (7KC) found at an increased level in the plasma of atherosclerotic patients and to simultaneously analyze their cytotoxic, proinflammatory and oxidative properties. STUDY DESIGN Flow cytometry (FCM), confocal laser scanning microscopy and subsequent factor analysis image processing were used to characterize the uptake of nanoparticles and to define their cytotoxicity, evaluated by enhanced permeability to SYTOX Green, release of lactate dehydrogenase (LDH) and morphologic nuclear changes determined with Hoechst 33342. Proinflammatory effects were estimated by enzyme linked immunoassay to quantify IL-8 and MCP-1 secretion. The overproduction of reactive oxygen species (ROS) was determined by FCM with hydroethidine. RESULTS Whereas the nanoparticles had no cytotoxic or inflammatory effects, they could stimulate ROS...
Écrit par et pour des francophones, cet ouvrage vous invite à découvrir la langue turque de façon... more Écrit par et pour des francophones, cet ouvrage vous invite à découvrir la langue turque de façon ludique et efficace, depuis la prononciation de l'alphabet jusqu'à la construction de phrases complexes. Laissez-vous guider par le titre de chacune des 45 leçons pour comprendre la grammaire et la conjugaison. Mettez en pratique immédiatement vos connaissances dans les exercices correspondants.
Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology, 2009
To evaluate the capture of nanoparticles (quantum dots [QDs], fluorospheres) by nonbeating mouse ... more To evaluate the capture of nanoparticles (quantum dots [QDs], fluorospheres) by nonbeating mouse cardiac cells (HL1-NB) cultured without or with 7-ketocholesterol (7KC) found at an increased level in the plasma of atherosclerotic patients and to simultaneously analyze their cytotoxic, proinflammatory and oxidative properties. Flow cytometry (FCM), confocal laser scanning microscopy and subsequent factor analysis image processing were used to characterize the uptake of nanoparticles and to define their cytotoxicity, evaluated by enhanced permeability to SYTOX Green, release of lactate dehydrogenase (LDH) and morphologic nuclear changes determined with Hoechst 33342. Proinflammatory effects were estimated by enzyme linked immunoassay to quantify IL-8 and MCP-1 secretion. The overproduction of reactive oxygen species (ROS) was determined by FCM with hydroethidine. Whereas the nanoparticles had no cytotoxic or inflammatory effects, they could stimulate ROS production. QDs were not incor...
Canadian Journal of Physiology and Pharmacology, 2009
Comparative analysis of the bioenergetic parameters of adult rat cardiomyocytes (CM) and HL-1 cel... more Comparative analysis of the bioenergetic parameters of adult rat cardiomyocytes (CM) and HL-1 cells with very different structure but similar cardiac phenotype was carried out with the aim of revealing the importance of the cell structure for regulation of its energy fluxes. Confocal microscopic analysis showed very different mitochondrial arrangement in these cells. The cytochrome content per milligram of cell protein was decreased in HL-1 cells by a factor of 7 compared with CM. In parallel, the respiratory chain complex activities were decreased by 4–8 times in the HL-1 cells. On the contrary, the activities of glycolytic enzymes, hexokinase (HK), and pyruvate kinase (PK) were increased in HL-1 cells, and these cells effectively transformed glucose into lactate. At the same time, the creatine kinase (CK) activity was significantly decreased in HL-1 cells. In conclusion, the results of this study comply with the assumption that in contrast to CM in which oxidative phosphorylation ...
Le developpement de capacites de communication et de reflexivite dans le cadre de la relation med... more Le developpement de capacites de communication et de reflexivite dans le cadre de la relation medecin-patient fait partie des objectifs pedagogiques du deuxieme cycle des etudes medicales en France. La reforme du Certificat de Competence Clinique (arrete du 8 avril 2013) en demande l’evaluation sous la forme d’une mise en situation clinique aupres d’un patient ou d’une epreuve de simulation. Dans ce contexte nous avons mis en place des jeux de role de simulation relationnelle et nous sommes interesses aux conditions dans lesquelles ils permettent de developper les competences relationnelles. Une etude observationnelle a ete menee dans le cadre de l’enseignement de Sciences Humaines et Sociales aupres des 360 etudiants en troisieme annee de medecine de la Faculte Lyon Est en septembre 2015. Deux seances de jeux de role de 2h avec 4 synopsis de consultations de medecine generale chacune ont ete concues en tenant compte des recommandations de la Haute Autorite de Sante (HAS, 2012). Un ...
Peripheral venous catheter insertion is a procedural skill that every medical student should mast... more Peripheral venous catheter insertion is a procedural skill that every medical student should master. Training is often limited to a small number of students and is poorly evaluated. The objective of this study was to evaluate the performance of peer-assisted learning in comparison to instructor-led teaching for peripheral venous catheter insertion training. Students were randomized to the control group attending a traditional instructor-led training session (slideshow and demonstration by an anesthetist instructor, followed by training on a procedural simulator) or to the test group attending a peer-assisted training session (slideshow and demonstration video-recorded by the same instructor, followed by training on a procedural simulator). The primary endpoint was the performance of peripheral venous catheter insertion, assessed on procedural simulator one week later by blinded experts using a standardized 20-item grid. Students self-evaluated their confidence levels using a numeric 10-point scale. Eighty-six students were included, 73 of whom attended the assessment session. The median performance score was 12/20 [8-15] in the instructor-led teaching group versus 13/20 [11-15] in the peer-assisted learning group (P=0.430). Confidence levels improved significantly after the assessment session and were significantly higher in the peer-assisted learning group (7.6/10 [7.0-8.0] versus 7.0/10 [5.0-8.0], P=0.026). Peer-assisted learning is effective for peripheral venous catheter insertion training and can be as effective as instructor-led teaching. Given the large number of students to train, this finding is important for optimizing the cost-effectiveness of peripheral venous catheter insertion training.
Basé sur l'association de mots (noms, adjectifs, verbes), l'ouvrage se divise en quatre p... more Basé sur l'association de mots (noms, adjectifs, verbes), l'ouvrage se divise en quatre parties : la première consacrée aux règles générales ; la deuxième consacrée aux noms et aux adjectifs ; la troisième consacrée aux verbes ; la quatrième consacrée aux expressions idiomatiques. Au fil des pages, le lecteur maîtrisera les clés indispensables pour parler et écrire un turc courant et fluide.
Basé sur l'association de mots (noms, adjectifs, verbes), l'ouvrage se divise en quatre p... more Basé sur l'association de mots (noms, adjectifs, verbes), l'ouvrage se divise en quatre parties : la première consacrée aux règles générales ; la deuxième consacrée aux noms et aux adjectifs ; la troisième consacrée aux verbes ; la quatrième consacrée aux expressions idiomatiques. Au fil des pages, le lecteur maîtrisera les clés indispensables pour parler et écrire un turc courant et fluide.
Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology, 2009
To evaluate the capture of nanoparticles (quantum dots [QDs], fluorospheres) by nonbeating mouse ... more To evaluate the capture of nanoparticles (quantum dots [QDs], fluorospheres) by nonbeating mouse cardiac cells (HL1-NB) cultured without or with 7-ketocholesterol (7KC) found at an increased level in the plasma of atherosclerotic patients and to simultaneously analyze their cytotoxic, proinflammatory and oxidative properties. Flow cytometry (FCM), confocal laser scanning microscopy and subsequent factor analysis image processing were used to characterize the uptake of nanoparticles and to define their cytotoxicity, evaluated by enhanced permeability to SYTOX Green, release of lactate dehydrogenase (LDH) and morphologic nuclear changes determined with Hoechst 33342. Proinflammatory effects were estimated by enzyme linked immunoassay to quantify IL-8 and MCP-1 secretion. The overproduction of reactive oxygen species (ROS) was determined by FCM with hydroethidine. Whereas the nanoparticles had no cytotoxic or inflammatory effects, they could stimulate ROS production. QDs were not incor...
The present study discusses the role of structural organization of cardiac cells in determining t... more The present study discusses the role of structural organization of cardiac cells in determining the mechanisms of regulation of oxidative phosphorylation and interaction between mitochondria and ATPases. In permeabilized adult cardiomyocytes, the apparent K(m) (Michaelis-Menten constant) for ADP in the regulation of respiration is far higher than in mitochondria isolated from the myocardium. Respiration of mitochondria in permeabilized cardiomyocytes is effectively activated by endogenous ADP produced by ATPases from exogenous ATP, and the activation of respiration is associated with a decrease in the apparent K(m) for ATP in the regulation of ATPase activity compared with this parameter in the absence of oxidative phosphorylation. It has also been shown that a large fraction of the endogenous ADP stimulating respiration remains inaccessible for the exogenous ADP trapping system, consisting of pyruvate kinase and phosphoenolpyruvate, unless the mitochondrial structures are modified ...
HL-1, the first cell line with a cardiac phenotype for biological experiments, displays spontaneo... more HL-1, the first cell line with a cardiac phenotype for biological experiments, displays spontaneous electrophysiological and mechanical regular activity, and cyclic calcium movements. We isolated a derived line, devoid of transient movements, for confocal microscopy experiments. These cells do express cardiac proteins: connexin 43, the cardiac isoform of dihydropyridine receptors, desmin, and developmental myosin but have no sarcomeric arrangement. They still possess the electrophysiological characteristics and ionic currents of cardiac cells, among them the cardiac potassium current IKr. We also found diazoxide and glibenclamide sensitive potassium channels with properties similar to IK(ATP) in adult cardiac myocytes. The pacemaker current I(f) was not observed, in agreement with the cells showing excitability but lacking in pacemaker activity. The absence of movement is an advantage for studies which include changes of media in order to follow morphological changes under continuou...
Progress in Biophysics and Molecular Biology, 2006
HL-1, the first cell line with a cardiac phenotype for biological experiments, displays spontaneo... more HL-1, the first cell line with a cardiac phenotype for biological experiments, displays spontaneous electrophysiological and mechanical regular activity, and cyclic calcium movements. We isolated a derived line, devoid of transient movements, for confocal microscopy experiments. These cells do express cardiac proteins: connexin 43, the cardiac isoform of dihydropyridine receptors, desmin, and developmental myosin but have no sarcomeric arrangement. They still possess the electrophysiological characteristics and ionic currents of cardiac cells, among them the cardiac potassium current IKr. We also found diazoxide and glibenclamide sensitive potassium channels with properties similar to IK(ATP) in adult cardiac myocytes. The pacemaker current I(f) was not observed, in agreement with the cells showing excitability but lacking in pacemaker activity. The absence of movement is an advantage for studies which include changes of media in order to follow morphological changes under continuous perfusion. We observed however a basal spontaneous movement of mitochondria and we developed a method to quantify its amplitude using confocal microscopy. No mitochondrial depolarization could be detected when the membrane potential was measured by using very low light photomultiplier and confocal fluorescence imaging under the K(ATP) channel opener diazoxide. Thus cardiac pharmacological preconditioning by K(ATP) channel openers might involve other routes than mitochondrial K channels targeting.
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