The Experts below are selected from a list of 11679 Experts worldwide ranked by ideXlab platform
Sylvie Klieber - One of the best experts on this subject based on the ideXlab platform.
-
morphological behaviour and Metabolic Capacity of cryopreserved human primary hepatocytes cultivated in a perfused multiwell device
Xenobiotica, 2015Co-Authors: Aurelie Vivares, Michele Bremond, Patricia Moliner, Jean François Gallas, Géraldine Pénarier, Sandrine Sallelefort, Catherine Arabeyrefabre, Gerard Fabre, Sylvie KlieberAbstract:Abstract1. The quantitative prediction of the pharmacokinetic parameters of a drug from data obtained using human in vitro systems remains a significant challenge i.e. prediction of Metabolic clearance in humans and estimation of the relative contribution of enzymes involved in the clearance. This has become particularly problematic for low turnover compounds.2. Having human hepatocytes with stable cellular function over several days that adequately mimic the complexity of the physiological environment would be a major advance. Thus, we evaluated human hepatocytes, maintained in culture during 7 days in the microfluidic LiverChip™ system, in terms of morphological appearance, relative mRNA expression of phase I and II enzymes and transporters as a function of time, and Metabolic Capacity using probe substrates.3. The results showed that mRNA levels of the major genes for enzymes involved in drug metabolism were well-maintained over a 7-day period of culture. Furthermore, after 4 days of culture, in the Li...
-
Morphological behaviour and Metabolic Capacity of cryopreserved human primary hepatocytes cultivated in a perfused multiwell device
Xenobiotica, 2015Co-Authors: Aurelie Vivares, Sandrine Salle-lefort, Catherine Arabeyre-fabre, Robert Ngo, Michele Bremond, Patricia Moliner, Jean François Gallas, Géraldine Fabre, Géraldine Pénarier, Sylvie KlieberAbstract:Abstract 1. The quantitative prediction of the pharmacokinetic parameters of a drug from data obtained using human in vitro systems remains a significant challenge i.e. prediction of Metabolic clearance in humans and estimation of the relative contribution of enzymes involved in the clearance. This has become particularly problematic for low turnover compounds. 2. Having human hepatocytes with stable cellular function over several days that adequately mimic the complexity of the physiological environment would be a major advance. Thus, we evaluated human hepatocytes, maintained in culture during 7 days in the microfluidic LiverChip™ system, in terms of morphological appearance, relative mRNA expression of phase I and II enzymes and transporters as a function of time, and Metabolic Capacity using probe substrates. 3. The results showed that mRNA levels of the major genes for enzymes involved in drug metabolism were well-maintained over a 7-day period of culture. Furthermore, after 4 days of culture, in the Liverchip™ device, human hepatocytes exhibited higher or similar CYPs activities compared to 1 day of culture in 2D-static conditions. 4. The functional data were supported by light/electron microscopies and immunohistochemistry showing viable tissue structure and well-differentiated human hepatocytes: presence of cell junctions, glycogen storage, and bile canaliculi.
P Courtet - One of the best experts on this subject based on the ideXlab platform.
-
a combined high cyp2d6 cyp2c19 Metabolic Capacity is associated with the severity of suicide attempt as measured by objective circumstances
Pharmacogenomics Journal, 2015Co-Authors: E Penaslledo, Sebastien Guillaume, M E G Naranjo, A Delgado, Isabelle Jaussent, H Blascofontecilla, P CourtetAbstract:A combined high CYP2D6-CYP2C19 Metabolic Capacity is associated with the severity of suicide attempt as measured by objective circumstances
-
Increased Cyp2d6-cyp2c19 Metabolic Capacity: Relation to Suicide Attempt Severity as Measured by the Beck Sis-objective Circumstances.
European Psychiatry, 2015Co-Authors: Eva M Peñas-lledó, Sebastien Guillaume, M E G Naranjo, A Delgado, Isabelle Jaussent, P Courtet, H. Blasco-fontecilla, Adrián LlerenaAbstract:Introduction CYP2D6 and CYP2C19 are involved in the metabolism of widely used antidepressants and other drugs with psychotropic activity. They also participate in the metabolism of endogenous substrates, and are expressed in the brain. Objectives and Aims This study examined, for the first time, whether a high CYP2D6-CYP2C19 Metabolic Capacity combination increases the likelihood of suicidal intent severity in a large study cohort. Methods Survivors of a suicide attempt (n=587; 86.8% women) were genotyped for CYP2C19 (*2, *17) and CYP2D6 (*3, *4, *4xN, *5, *6, *10, wtxN) genetic variation and evaluated with the Beck Suicide Intent Scale (SIS). Results Patients with a high CYP2D6-CYP2C19 Metabolic Capacity showed an increased risk for a severe suicide attempt (P Conclusions Further research is warranted to evaluate whether the observed relationship is mediated by the role of CYP2D6 and CYP2C19 involvement in the endogenous physiology or drug metabolism or both. Acknoledgments This work was supported in part by Union Europea Fondo Social Europea (FEDER/FSE), Instituto de Salud Carlos III-FIS (PI10/02758) and Gobierno de Extremadura Consejeria de Economia, Competitividad e Innovacion (IB13186 and PD10199). CHU Montpellier (PHRC UF 7653), Agence Nationale de la Recherche (ANR NEURO 2007 'GENESIS').
Aurelie Vivares - One of the best experts on this subject based on the ideXlab platform.
-
morphological behaviour and Metabolic Capacity of cryopreserved human primary hepatocytes cultivated in a perfused multiwell device
Xenobiotica, 2015Co-Authors: Aurelie Vivares, Michele Bremond, Patricia Moliner, Jean François Gallas, Géraldine Pénarier, Sandrine Sallelefort, Catherine Arabeyrefabre, Gerard Fabre, Sylvie KlieberAbstract:Abstract1. The quantitative prediction of the pharmacokinetic parameters of a drug from data obtained using human in vitro systems remains a significant challenge i.e. prediction of Metabolic clearance in humans and estimation of the relative contribution of enzymes involved in the clearance. This has become particularly problematic for low turnover compounds.2. Having human hepatocytes with stable cellular function over several days that adequately mimic the complexity of the physiological environment would be a major advance. Thus, we evaluated human hepatocytes, maintained in culture during 7 days in the microfluidic LiverChip™ system, in terms of morphological appearance, relative mRNA expression of phase I and II enzymes and transporters as a function of time, and Metabolic Capacity using probe substrates.3. The results showed that mRNA levels of the major genes for enzymes involved in drug metabolism were well-maintained over a 7-day period of culture. Furthermore, after 4 days of culture, in the Li...
-
Morphological behaviour and Metabolic Capacity of cryopreserved human primary hepatocytes cultivated in a perfused multiwell device
Xenobiotica, 2015Co-Authors: Aurelie Vivares, Sandrine Salle-lefort, Catherine Arabeyre-fabre, Robert Ngo, Michele Bremond, Patricia Moliner, Jean François Gallas, Géraldine Fabre, Géraldine Pénarier, Sylvie KlieberAbstract:Abstract 1. The quantitative prediction of the pharmacokinetic parameters of a drug from data obtained using human in vitro systems remains a significant challenge i.e. prediction of Metabolic clearance in humans and estimation of the relative contribution of enzymes involved in the clearance. This has become particularly problematic for low turnover compounds. 2. Having human hepatocytes with stable cellular function over several days that adequately mimic the complexity of the physiological environment would be a major advance. Thus, we evaluated human hepatocytes, maintained in culture during 7 days in the microfluidic LiverChip™ system, in terms of morphological appearance, relative mRNA expression of phase I and II enzymes and transporters as a function of time, and Metabolic Capacity using probe substrates. 3. The results showed that mRNA levels of the major genes for enzymes involved in drug metabolism were well-maintained over a 7-day period of culture. Furthermore, after 4 days of culture, in the Liverchip™ device, human hepatocytes exhibited higher or similar CYPs activities compared to 1 day of culture in 2D-static conditions. 4. The functional data were supported by light/electron microscopies and immunohistochemistry showing viable tissue structure and well-differentiated human hepatocytes: presence of cell junctions, glycogen storage, and bile canaliculi.
Frank Seebacher - One of the best experts on this subject based on the ideXlab platform.
-
Beneficial acclimation: sex specific thermal acclimation of Metabolic Capacity in the striped marsh frog (Limnodynastes peronii).
The Journal of experimental biology, 2020Co-Authors: Kris D Rogers, Michael B Thompson, Frank SeebacherAbstract:Reproductive success in thermally varying environments will depend on maintaining Metabolic Capacity of tissues that are important in mating behaviours. Here we test the hypothesis that cold acclimation will occur in those tissues that are important for reproduction, and that acclimation will be sex specific, reflecting behavioural differences between the sexes. We used the frog Limnodynastes peronii as a model because anurans engage in energetically demanding reproductive behaviour, and many species, including L. peronii, are reproductively active across seasons. Additionally, reproductive behaviours such as calling and amplexus are sex specific. We acclimated animals to naturally occurring autumn (15 degrees C, N=10) and summer (25 degrees C, N=10) temperatures. Whole-animal resting oxygen consumption decreased with lowered temperature, but there was no difference in oxygen consumption between acclimation treatments or sexes. However, the respiratory control ratio (RCR) of mitochondria from the liver and external oblique calling muscle increased with cold acclimation. The increase in RCR with thermal acclimation was due to upregulation of state 3 respiration, and not to a decrease in state 4 respiration. Males had higher activity of citrate synthase, beta-hydroxyacyl CoA dehydrogenase and cytochrome c oxidase than females in the calling (external oblique) muscle, and males also showed thermal acclimation of these enzymes while females did not. Additionally, males had greater activity of Metabolic enzymes in the principal muscle (extensor carpi radialis) used during amplexus. However, there were no differences in Metabolic Capacity between sexes in the gastrocnemius muscle and in liver, and both sexes showed significant acclimation of lactate dehydrogenase and cytochrome c oxidase in the former and latter, respectively. In L. peronii, thermal acclimation of Metabolic capacities is linked to reproductive success, and reversible phenotypic plasticity therefore confers a selective advantage by extending the temporal and spatial extent of the animals' fundamental niche.
-
Plasticity in body temperature and Metabolic Capacity sustains winter activity in a small endotherm (Rattus fuscipes)
Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, 2009Co-Authors: Elsa J. Glanville, Frank SeebacherAbstract:Abstract Small mammals that remain active throughout the year at a constant body temperature have a much greater energy and food requirement in winter. Lower body temperatures in winter may offset the increased energetic cost of remaining active in the cold, if cellular metabolism is not constrained by a negative thermodynamic effect. We aimed to determine whether variable body temperatures can be advantageous for small endotherms by testing the hypothesis that body temperature fluctuates seasonally in a wild rat (Rattus fuscipes); conferring an energy saving and reducing food requirements during resource restricted winter. Additionally we tested whether changes in body temperature affected tissue specific Metabolic Capacity. Winter acclimatized rats had significantly lower body temperatures and thicker fur than summer acclimatized rats. Mitochondrial oxygen consumption and the activity of enzymes that control oxidative (citrate synthase, cytochrome c-oxidase) and anaerobic (lactate dehydrogenase) metabolism were elevated in winter and were not negatively affected by the lower body temperature. Energy transfer modeling showed that lower body temperatures in winter combined with increased fur thickness to confer a 25 kJ day− 1 energy saving, with up to 50% owing to reduced body temperature alone. We show that phenotypic plasticity at multiple levels of organization is an important component of the response of a small endotherm to winter. Mitochondrial function compensates for lower winter body temperatures, buffering Metabolic heat production Capacity.
-
Beneficial acclimation: sex specific thermal acclimation of Metabolic Capacity in the striped marsh frog (Limnodynastes peronii).
The Journal of Experimental Biology, 2007Co-Authors: Kris Rogers, Michael B Thompson, Frank SeebacherAbstract:SUMMARY Reproductive success in thermally varying environments will depend on maintaining Metabolic Capacity of tissues that are important in mating behaviours. Here we test the hypothesis that cold acclimation will occur in those tissues that are important for reproduction, and that acclimation will be sex specific, reflecting behavioural differences between the sexes. We used the frog Limnodynastes peronii as a model because anurans engage in energetically demanding reproductive behaviour, and many species, including L. peronii , are reproductively active across seasons. Additionally, reproductive behaviours such as calling and amplexus are sex specific. We acclimated animals to naturally occurring autumn (15°C, N =10) and summer (25°C, N =10) temperatures. Whole-animal resting oxygen consumption decreased with lowered temperature, but there was no difference in oxygen consumption between acclimation treatments or sexes. However, the respiratory control ratio (RCR) of mitochondria from the liver and external oblique calling muscle increased with cold acclimation. The increase in RCR with thermal acclimation was due to upregulation of state 3 respiration, and not to a decrease in state 4 respiration. Males had higher activity of citrate synthase, β-hydroxyacyl CoA dehydrogenase and cytochrome c oxidase than females in the calling (external oblique) muscle, and males also showed thermal acclimation of these enzymes while females did not. Additionally, males had greater activity of Metabolic enzymes in the principal muscle (extensor carpi radialis) used during amplexus. However, there were no differences in Metabolic Capacity between sexes in the gastrocnemius muscle and in liver, and both sexes showed significant acclimation of lactate dehydrogenase and cytochrome c oxidase in the former and latter, respectively. In L. peronii , thermal acclimation of Metabolic capacities is linked to reproductive success, and reversible phenotypic plasticity therefore confers a selective advantage by extending the temporal and spatial extent of the animals9 fundamental niche.
-
Transition from ectothermy to endothermy: the development of Metabolic Capacity in a bird (Gallus gallus)
Proceedings of The Royal Society B: Biological Sciences, 2005Co-Authors: Frank Seebacher, Tonia S. Schwartz, Michael B ThompsonAbstract:The evolution of endothermy is one of the most significant events in vertebrate evolution. Adult mammals and birds are delineated from their early ontogenetic stages, as well as from other vertebrates, by high resting Metabolic rates and consequent internal heat production. We used the embryonic development of a bird (Gallus gallus) as a model to investigate the Metabolic transition between ectothermy and endothermy. Increases in aerobic Capacity occur at two functional levels that are regulated independently from each other: (i) upregulation of gene expression; and (ii) significant increases in the catalytic activity of the main oxidative control enzymes. Anaerobic Capacity, measured as lactate dehydrogenase activity, is extremely high during early development, but diminishes at the same time as aerobic Capacity increases. Changes in lactate dehydrogenase activity are independent from its gene expression. The regulatory mechanisms that lead to endothermic Metabolic Capacity are similar to those of ectotherms in their response to environmental change. We suggest that the phylogenetic occurrence of endothermy is restricted by its limited selective advantages rather than by evolutionary innovation.
Hendrik Vilstrup - One of the best experts on this subject based on the ideXlab platform.
-
the clinical course of alcoholic cirrhosis effects of hepatic Metabolic Capacity alcohol consumption and hyponatremia a historical cohort study
BMC Research Notes, 2012Co-Authors: Peter Uhd Jepsen, Per Kragh Andersen, Hendrik VilstrupAbstract:Background The cirrhosis complications hepatic encephalopathy, ascites, and variceal bleeding increase mortality but develop in random sequence. Therefore prognoses based on the presence or absence of these clinical complications are inherently inaccurate, and other determinants of the clinical course should be identified. Here we present our study of patho-etiological factors that may be causally involved in the development of specific complications to alcoholic cirrhosis; it was based on a model of cirrhosis pathophysiology encompassing hepatic Metabolic Capacity, continued alcohol consumption, and circulatory dysfunction.
-
The clinical course of alcoholic cirrhosis: effects of hepatic Metabolic Capacity, alcohol consumption, and hyponatremia – a historical cohort study
BMC Research Notes, 2012Co-Authors: Peter Uhd Jepsen, Per Kragh Andersen, Hendrik VilstrupAbstract:Background The cirrhosis complications hepatic encephalopathy, ascites, and variceal bleeding increase mortality but develop in random sequence. Therefore prognoses based on the presence or absence of these clinical complications are inherently inaccurate, and other determinants of the clinical course should be identified. Here we present our study of patho-etiological factors that may be causally involved in the development of specific complications to alcoholic cirrhosis; it was based on a model of cirrhosis pathophysiology encompassing hepatic Metabolic Capacity, continued alcohol consumption, and circulatory dysfunction.