The Experts below are selected from a list of 477 Experts worldwide ranked by ideXlab platform
Maurizio Taglialatela - One of the best experts on this subject based on the ideXlab platform.
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expression and motor functional roles of voltage dependent type 7 k channels in the human taenia coli
European Journal of Pharmacology, 2013Co-Authors: Alice Adduci, Gianluca Rizzo, Claudio Coco, Maurizio Taglialatela, Maria Martire, Vincenzo Arena, Diego CurròAbstract:Abstract Voltage-dependent type 7 K + (K V 7 or KCNQ) channels modulate the excitability of neurons and muscle cells. The aims of the present study were to investigate the motor effects of K V 7 channel modulators and the expression of K V 7 channels in the human taenia coli . The effects of K V 7 channel modulators on the muscle tone of human taenia coli strips were investigated under nonadrenergic non-nitrergic conditions by organ bath studies. Gene expression and tissue localisation of channels were studied by real-time PCR and immunohistochemistry, respectively. Under basal conditions, the K V 7 channel blocker XE-991 induced concentration-dependent contractions, with mean EC 50 and E max of 18.7 μM and 30.5% respectively of the maximal bethanechol-induced contraction, respectively. The K V 7 channel activators retigabine and Flupirtine concentration-dependently relaxed the taenia coli , with mean EC 50 s of 19.2 μM and 29.9 μM, respectively. Retigabine also relaxed bethanechol-precontracted strips, with maximal relaxations of 79.2% of the bethanecol-induced precontraction. The motor effects induced by the K V 7 channel modulators were not affected by tetrodotoxin or ω-conotoxin GVIA. XE-991 greatly reduced retigabine- and Flupirtine-induced relaxations. Transcripts encoded by all KCNQ genes were detected in the taenia coli , with KCNQ4 showing the highest expression levels. K V 7.4 channels were clearly visualised by immunohistochemistry in colonic epithelium, circular muscle layer and taenia coli . K V 7 channels appear to contribute to the resting muscle tone of the human taenia coli . In addition, K V 7 channel activators significantly relax the taenia coli . Thus, they could be useful therapeutic relaxant agents for colonic motor disorders.
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Expression and motor functional roles of voltage-dependent type 7 K(+) channels in the human taenia coli.
European journal of pharmacology, 2013Co-Authors: Alice Adduci, Gianluca Rizzo, Claudio Coco, Maurizio Taglialatela, Maria Martire, Vincenzo Arena, Diego CurròAbstract:Voltage-dependent type 7 K(+) (KV7 or KCNQ) channels modulate the excitability of neurons and muscle cells. The aims of the present study were to investigate the motor effects of KV7 channel modulators and the expression of KV7 channels in the human taenia coli. The effects of KV7 channel modulators on the muscle tone of human taenia coli strips were investigated under nonadrenergic non-nitrergic conditions by organ bath studies. Gene expression and tissue localisation of channels were studied by real-time PCR and immunohistochemistry, respectively. Under basal conditions, the KV7 channel blocker XE-991 induced concentration-dependent contractions, with mean EC50 and Emax of 18.7 μM and 30.5% respectively of the maximal bethanechol-induced contraction, respectively. The KV7 channel activators retigabine and Flupirtine concentration-dependently relaxed the taenia coli, with mean EC50s of 19.2 μM and 29.9 μM, respectively. Retigabine also relaxed bethanechol-precontracted strips, with maximal relaxations of 79.2% of the bethanecol-induced precontraction. The motor effects induced by the KV7 channel modulators were not affected by tetrodotoxin or ω-conotoxin GVIA. XE-991 greatly reduced retigabine- and Flupirtine-induced relaxations. Transcripts encoded by all KCNQ genes were detected in the taenia coli, with KCNQ4 showing the highest expression levels. KV7.4 channels were clearly visualised by immunohistochemistry in colonic epithelium, circular muscle layer and taenia coli. KV7 channels appear to contribute to the resting muscle tone of the human taenia coli. In addition, KV7 channel activators significantly relax the taenia coli. Thus, they could be useful therapeutic relaxant agents for colonic motor disorders.
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retigabine and Flupirtine exert neuroprotective actions in organotypic hippocampal cultures
Neuropharmacology, 2006Co-Authors: Francesca Boscia, Maurizio Taglialatela, Lucio AnnunziatoAbstract:Abstract Retigabine and Flupirtine are two structurally related molecules provided of anticonvulsant and analgesic actions. The present study has investigated the neuroprotective potential, as well as the possible underlying molecular mechanisms, exerted by retigabine and Flupirtine in rat organotypic hippocampal slice cultures (OHSCs) exposed to N-methyl- d -aspartate (NMDA), oxygen and glucose deprivation followed by reoxygenation (OGD), or serum withdrawal (SW). Region-specific vulnerability of hippocampal subfields occurred with each of these injury models. Specifically, CA1 was the most susceptible region to both NMDA and OGD-induced neurodegeneration, whereas selective cell death in the dentate gyrus (DG) occurred upon OHSCs exposure to SW. The NMDA antagonist MK-801 (10–30 μM), despite blocking NMDA- and OGD-induced cell death, failed to prevent SW-induced neurodegeneration. Interestingly, retigabine (0.01–10 μM) and Flupirtine (0.01–10 μM) dose-dependently prevented DG neuronal death induced by SW, with IC50 s of 0.4 μM and 0.7 μM, respectively. By contrast, retigabine and Flupirtine (each at 10 μM) were less effective in counteracting NMDA- or OGD-induced toxicity in the CA1 region. Both retigabine and Flupirtine (0.1–10 μM) reduced SW-induced ROS production in the DG with IC50 s of ≈1 μM. This suggested that antioxidant actions of these compounds participated in OHSC neuroprotection during SW. By contrast, activation of KCNQ K+ channels seemed not to be involved in retigabine-induced OHSCs neuroprotection during SW, since linopirdine (20 μM) and XE-991 (10 μM), two KCNQ blockers, failed to reverse retigabine-induced neuronal rescue.
Diego Currò - One of the best experts on this subject based on the ideXlab platform.
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expression and motor functional roles of voltage dependent type 7 k channels in the human taenia coli
European Journal of Pharmacology, 2013Co-Authors: Alice Adduci, Gianluca Rizzo, Claudio Coco, Maurizio Taglialatela, Maria Martire, Vincenzo Arena, Diego CurròAbstract:Abstract Voltage-dependent type 7 K + (K V 7 or KCNQ) channels modulate the excitability of neurons and muscle cells. The aims of the present study were to investigate the motor effects of K V 7 channel modulators and the expression of K V 7 channels in the human taenia coli . The effects of K V 7 channel modulators on the muscle tone of human taenia coli strips were investigated under nonadrenergic non-nitrergic conditions by organ bath studies. Gene expression and tissue localisation of channels were studied by real-time PCR and immunohistochemistry, respectively. Under basal conditions, the K V 7 channel blocker XE-991 induced concentration-dependent contractions, with mean EC 50 and E max of 18.7 μM and 30.5% respectively of the maximal bethanechol-induced contraction, respectively. The K V 7 channel activators retigabine and Flupirtine concentration-dependently relaxed the taenia coli , with mean EC 50 s of 19.2 μM and 29.9 μM, respectively. Retigabine also relaxed bethanechol-precontracted strips, with maximal relaxations of 79.2% of the bethanecol-induced precontraction. The motor effects induced by the K V 7 channel modulators were not affected by tetrodotoxin or ω-conotoxin GVIA. XE-991 greatly reduced retigabine- and Flupirtine-induced relaxations. Transcripts encoded by all KCNQ genes were detected in the taenia coli , with KCNQ4 showing the highest expression levels. K V 7.4 channels were clearly visualised by immunohistochemistry in colonic epithelium, circular muscle layer and taenia coli . K V 7 channels appear to contribute to the resting muscle tone of the human taenia coli . In addition, K V 7 channel activators significantly relax the taenia coli . Thus, they could be useful therapeutic relaxant agents for colonic motor disorders.
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Expression and motor functional roles of voltage-dependent type 7 K(+) channels in the human taenia coli.
European journal of pharmacology, 2013Co-Authors: Alice Adduci, Gianluca Rizzo, Claudio Coco, Maurizio Taglialatela, Maria Martire, Vincenzo Arena, Diego CurròAbstract:Voltage-dependent type 7 K(+) (KV7 or KCNQ) channels modulate the excitability of neurons and muscle cells. The aims of the present study were to investigate the motor effects of KV7 channel modulators and the expression of KV7 channels in the human taenia coli. The effects of KV7 channel modulators on the muscle tone of human taenia coli strips were investigated under nonadrenergic non-nitrergic conditions by organ bath studies. Gene expression and tissue localisation of channels were studied by real-time PCR and immunohistochemistry, respectively. Under basal conditions, the KV7 channel blocker XE-991 induced concentration-dependent contractions, with mean EC50 and Emax of 18.7 μM and 30.5% respectively of the maximal bethanechol-induced contraction, respectively. The KV7 channel activators retigabine and Flupirtine concentration-dependently relaxed the taenia coli, with mean EC50s of 19.2 μM and 29.9 μM, respectively. Retigabine also relaxed bethanechol-precontracted strips, with maximal relaxations of 79.2% of the bethanecol-induced precontraction. The motor effects induced by the KV7 channel modulators were not affected by tetrodotoxin or ω-conotoxin GVIA. XE-991 greatly reduced retigabine- and Flupirtine-induced relaxations. Transcripts encoded by all KCNQ genes were detected in the taenia coli, with KCNQ4 showing the highest expression levels. KV7.4 channels were clearly visualised by immunohistochemistry in colonic epithelium, circular muscle layer and taenia coli. KV7 channels appear to contribute to the resting muscle tone of the human taenia coli. In addition, KV7 channel activators significantly relax the taenia coli. Thus, they could be useful therapeutic relaxant agents for colonic motor disorders.
Thomas Stammschulte - One of the best experts on this subject based on the ideXlab platform.
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hla drb1 16 01 dqb1 05 02 is a novel genetic risk factor for Flupirtine induced liver injury
Pharmacogenetics and Genomics, 2016Co-Authors: Paola Nicoletti, Einar Bjornsson, Anneke Werk, Ashley Sawle, Yufeng Shen, Ingolf Cascorbi, Aris Floratos, Thomas J Urban, Sally A Coulthard, Thomas StammschulteAbstract:ObjectiveFlupirtine is a nonopioid analgesic with regulatory approval in a number of European countries. Because of the risk of serious liver injury, its use is now limited to short-term pain management. We aimed to identify genetic risk factors for Flupirtine-related drug-induced liver injury (DILI
Alice Adduci - One of the best experts on this subject based on the ideXlab platform.
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expression and motor functional roles of voltage dependent type 7 k channels in the human taenia coli
European Journal of Pharmacology, 2013Co-Authors: Alice Adduci, Gianluca Rizzo, Claudio Coco, Maurizio Taglialatela, Maria Martire, Vincenzo Arena, Diego CurròAbstract:Abstract Voltage-dependent type 7 K + (K V 7 or KCNQ) channels modulate the excitability of neurons and muscle cells. The aims of the present study were to investigate the motor effects of K V 7 channel modulators and the expression of K V 7 channels in the human taenia coli . The effects of K V 7 channel modulators on the muscle tone of human taenia coli strips were investigated under nonadrenergic non-nitrergic conditions by organ bath studies. Gene expression and tissue localisation of channels were studied by real-time PCR and immunohistochemistry, respectively. Under basal conditions, the K V 7 channel blocker XE-991 induced concentration-dependent contractions, with mean EC 50 and E max of 18.7 μM and 30.5% respectively of the maximal bethanechol-induced contraction, respectively. The K V 7 channel activators retigabine and Flupirtine concentration-dependently relaxed the taenia coli , with mean EC 50 s of 19.2 μM and 29.9 μM, respectively. Retigabine also relaxed bethanechol-precontracted strips, with maximal relaxations of 79.2% of the bethanecol-induced precontraction. The motor effects induced by the K V 7 channel modulators were not affected by tetrodotoxin or ω-conotoxin GVIA. XE-991 greatly reduced retigabine- and Flupirtine-induced relaxations. Transcripts encoded by all KCNQ genes were detected in the taenia coli , with KCNQ4 showing the highest expression levels. K V 7.4 channels were clearly visualised by immunohistochemistry in colonic epithelium, circular muscle layer and taenia coli . K V 7 channels appear to contribute to the resting muscle tone of the human taenia coli . In addition, K V 7 channel activators significantly relax the taenia coli . Thus, they could be useful therapeutic relaxant agents for colonic motor disorders.
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Expression and motor functional roles of voltage-dependent type 7 K(+) channels in the human taenia coli.
European journal of pharmacology, 2013Co-Authors: Alice Adduci, Gianluca Rizzo, Claudio Coco, Maurizio Taglialatela, Maria Martire, Vincenzo Arena, Diego CurròAbstract:Voltage-dependent type 7 K(+) (KV7 or KCNQ) channels modulate the excitability of neurons and muscle cells. The aims of the present study were to investigate the motor effects of KV7 channel modulators and the expression of KV7 channels in the human taenia coli. The effects of KV7 channel modulators on the muscle tone of human taenia coli strips were investigated under nonadrenergic non-nitrergic conditions by organ bath studies. Gene expression and tissue localisation of channels were studied by real-time PCR and immunohistochemistry, respectively. Under basal conditions, the KV7 channel blocker XE-991 induced concentration-dependent contractions, with mean EC50 and Emax of 18.7 μM and 30.5% respectively of the maximal bethanechol-induced contraction, respectively. The KV7 channel activators retigabine and Flupirtine concentration-dependently relaxed the taenia coli, with mean EC50s of 19.2 μM and 29.9 μM, respectively. Retigabine also relaxed bethanechol-precontracted strips, with maximal relaxations of 79.2% of the bethanecol-induced precontraction. The motor effects induced by the KV7 channel modulators were not affected by tetrodotoxin or ω-conotoxin GVIA. XE-991 greatly reduced retigabine- and Flupirtine-induced relaxations. Transcripts encoded by all KCNQ genes were detected in the taenia coli, with KCNQ4 showing the highest expression levels. KV7.4 channels were clearly visualised by immunohistochemistry in colonic epithelium, circular muscle layer and taenia coli. KV7 channels appear to contribute to the resting muscle tone of the human taenia coli. In addition, KV7 channel activators significantly relax the taenia coli. Thus, they could be useful therapeutic relaxant agents for colonic motor disorders.
Stammschulte Thomas - One of the best experts on this subject based on the ideXlab platform.
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HLA-DRB1*16:01-DQB1*05:02 is a novel genetic risk factor for Flupirtine-induced liver injury
'Ovid Technologies (Wolters Kluwer Health)', 2016Co-Authors: Nicoletti Paola, Werk, Anneke N., Sawle Ashley, Shen Yufeng, Urban, Thomas J., Coulthard, Sally A., Bjornsson, Einar S., Cascorbi Ingolf, Floratos Aris, Stammschulte ThomasAbstract:Objective Flupirtine is a nonopioid analgesic with regulatory approval in a number of European countries. Because of the risk of serious liver injury, its use is now limited to short-term pain management. We aimed to identify genetic risk factors for Flupirtine-related drug-induced liver injury (DILI) as these are unknown. Materials and methods Six Flupirtine-related DILI patients from Germany were included in a genome-wide association study (GWAS) involving a further 614 European cases of DILI because of other drugs and 10588 population controls. DILI was diagnosed by causality assessment and expert review. Human leucocyte antigen (HLA) and single nucleotide polymorphism genotypes were imputed from the GWAS data, with direct HLA typing performed on selected cases to validate HLA predictions. Four replication cases that were unavailable for the GWAS were genotyped by direct HLA typing, yielding an overall total of 10 Flupirtine DILI cases. Results In the six Flupirtine DILI cases included in the GWAS, we found a significant enrichment of the DRB1*16:01-DQB1*05:02 haplotype compared with the controls (minor allele frequency cases 0.25 and minor allele frequency controls 0.013; P=1.4x10(-5)). We estimated an odds ratio for haplotype carriers of 18.7 (95% confidence interval 2.5-140.5, P=0.002) using population-specific HLA control data. The result was replicated in four additional cases, also with a haplotype frequency of 0.25. In the combined cohort (six GWAS plus four replication cases), the haplotype was also significant (odds ratio 18.7, 95% confidence interval 4.31-81.42, P=6.7x10(-5)). Conclusion We identified a novel HLA class II association for DILI, confirming the important contribution of HLA genotype towards the risk of DILI generally. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserve
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HLA-DRB1*16: 01-DQB1*05: 02 is a novel genetic risk factor for Flupirtine-induced liver injury.
'Ovid Technologies (Wolters Kluwer Health)', 2016Co-Authors: Nicoletti Paola, Sawle Ashley, Shen Yufeng, Cascorbi Ingolf, Floratos Aris, Werk Anneke, Urban Thomas, Coulthard Sally, Björnsson Einar, Stammschulte ThomasAbstract:International audienceOBJECTIVE:Flupirtine is a nonopioid analgesic with regulatory approval in a number of European countries. Because of the risk of serious liver injury, its use is now limited to short-term pain management. We aimed to identify genetic risk factors for Flupirtine-related drug-induced liver injury (DILI) as these are unknown.MATERIALS AND METHODS:Six Flupirtine-related DILI patients from Germany were included in a genome-wide association study (GWAS) involving a further 614 European cases of DILI because of other drugs and 10,588 population controls. DILI was diagnosed by causality assessment and expert review. Human leucocyte antigen (HLA) and single nucleotide polymorphism genotypes were imputed from the GWAS data, with direct HLA typing performed on selected cases to validate HLA predictions. Four replication cases that were unavailable for the GWAS were genotyped by direct HLA typing, yielding an overall total of 10 Flupirtine DILI cases.RESULTS:In the six Flupirtine DILI cases included in the GWAS, we found a significant enrichment of the DRB1*16:01-DQB1*05:02 haplotype compared with the controls (minor allele frequency cases 0.25 and minor allele frequency controls 0.013; P=1.4 × 10(-5)). We estimated an odds ratio for haplotype carriers of 18.7 (95% confidence interval 2.5-140.5, P=0.002) using population-specific HLA control data. The result was replicated in four additional cases, also with a haplotype frequency of 0.25. In the combined cohort (six GWAS plus four replication cases), the haplotype was also significant (odds ratio 18.7, 95% confidence interval 4.31-81.42, P=6.7 × 10(-5)).CONCLUSION:We identified a novel HLA class II association for DILI, confirming the important contribution of HLA genotype towards the risk of DILI generally
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HLA-DRB1*16: 01-DQB1*05: 02 is a novel genetic risk factor for Flupirtine-induced liver injury.
'Ovid Technologies (Wolters Kluwer Health)', 2016Co-Authors: Nicoletti Paola, Werk, Anneke N., Sawle Ashley, Shen Yufeng, Urban, Thomas J., Coulthard, Sally A., Bjornsson, Einar S., Cascorbi Ingolf, Floratos Aris, Stammschulte ThomasAbstract:To access publisher's full text version of this article click on the hyperlink at the bottom of the pageFlupirtine is a nonopioid analgesic with regulatory approval in a number of European countries. Because of the risk of serious liver injury, its use is now limited to short-term pain management. We aimed to identify genetic risk factors for Flupirtine-related drug-induced liver injury (DILI) as these are unknown.Six Flupirtine-related DILI patients from Germany were included in a genome-wide association study (GWAS) involving a further 614 European cases of DILI because of other drugs and 10 588 population controls. DILI was diagnosed by causality assessment and expert review. Human leucocyte antigen (HLA) and single nucleotide polymorphism genotypes were imputed from the GWAS data, with direct HLA typing performed on selected cases to validate HLA predictions. Four replication cases that were unavailable for the GWAS were genotyped by direct HLA typing, yielding an overall total of 10 Flupirtine DILI cases.In the six Flupirtine DILI cases included in the GWAS, we found a significant enrichment of the DRB1*16:01-DQB1*05:02 haplotype compared with the controls (minor allele frequency cases 0.25 and minor allele frequency controls 0.013; P=1.4×10). We estimated an odds ratio for haplotype carriers of 18.7 (95% confidence interval 2.5-140.5, P=0.002) using population-specific HLA control data. The result was replicated in four additional cases, also with a haplotype frequency of 0.25. In the combined cohort (six GWAS plus four replication cases), the haplotype was also significant (odds ratio 18.7, 95% confidence interval 4.31-81.42, P=6.7×10).We identified a novel HLA class II association for DILI, confirming the important contribution of HLA genotype towards the risk of DILI generally.International Serious Adverse Events Consortium Abbott Amgen Daiichi-Sankyo GlaxoSmithKline Merck Novartis Pfizer Roche Sanofi-Aventis Takeda Wellcome Trust National Institute for Health Research (NIHR) Nottingham Digestive Diseases Biomedical Research Unit at the Nottingham University Hospitals NHS Trust University of Nottingha