The Experts below are selected from a list of 174 Experts worldwide ranked by ideXlab platform
Adelar Bracht - One of the best experts on this subject based on the ideXlab platform.
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Transport, transformation and Distribution Space of propofol in the rat liver studied by means of the indicator-dilution technique
Xenobiotica; the fate of foreign compounds in biological systems, 2004Co-Authors: Alexandra Acco, Adelar BrachtAbstract:The transport, transformation and Distribution Space of the endovenous anaesthetic propofol in the isolated perfused rat liver were investigated by using the multiple-indicator dilution technique with constant infusion (step input).The behaviour of propofol in the liver was described by a Space-distributed variable transit-time model. The drug permeated the cell membrane at very high rates and its Distribution into the cellular Space was flow-limited. The apparent Distribution Space of propofol varied between 284 and 125 times the water Space, and was inversely related to the tested portal concentrations (33–250 µM).The corresponding ratios of intra- to extracellular concentration varied between 319 and 187, revealing a very high affinity of the liver for propofol. They most probably reflect binding to several cellular structures, including membranes and proteins.The single-pass rate coefficients for biotransformation decreased with increases in the portal concentration of propofol. The liver released sig...
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Metabolic effects and Distribution Space of flufenamic acid in the isolated perfused rat liver
Chemico-Biological Interactions, 1998Co-Authors: Carlos Lopez, Adelar Bracht, N S Yamamoto, Mariana D. Dos SantosAbstract:Abstract The following aspects were investigated in the present work: (a) the action of flufenamic acid on hepatic metabolism (oxygen uptake, glycolysis, gluconeogenesis, uricogenesis and glycogenolysis), (b) the action of flufenamic acid on the cellular adenine nucleotide levels, and (c) the transport and Distribution Space of flufenamic acid in the liver parenchyma. The experimental system was the isolated perfused rat liver. Perfusion was accomplished in an open, non-recirculating system. The perfusion fluid was Krebs/Henseleit-bicarbonate buffer (pH 7.4), saturated with a mixture of oxygen and carbon dioxide (95:5) by means of a membrane oxygenator and heated to 37°C. The Distribution Space of flufenamic acid was measured by means of the multiple-indicator dilution technique with constant infusion (step input) of [ 3 H]water plus flufenamic acid. The results of the present work indicate that the metabolic effects of flufenamic acid are the consequence of an uncoupling of oxidative phosphorylation, a conclusion based on the following observations: (a) flufenamic acid increased oxygen uptake, a common property of all uncouplers; (b) the drug also increased glycolysis and glycogenolysis in livers from fed rats (these are expected compensatory phenomena for the decreased mitochondrial ATP formation); (c) flufenamic acid inhibited glucose production from fructose, an energy-dependent process; (d) the cellular ATP levels were decreased by flufenamic acid whereas the AMP levels were increased; and (e) the total adenine nucleotide content was decreased by flufenamic acid and uric acid production was stimulated. Indicator-dilution experiments with flufenamic acid revealed that this substance undergoes flow-limited Distribution in the liver and that its apparent Distribution Space greatly exceeds the aqueous Space of the liver. Flufenamic acid changed its behaviour when the portal concentration was increased from 25 to 50 μ M. At 25 μ M the initial upslope of the outflow profile clearly preceded that of all other concentrations. From the trend of the curves obtained with 50, 100 and 250 μ M, one would expect an initial upslope situated at the right of the 50- μ M curve. Furthermore, the time of appearance of flufenamic acid in the outflowing perfusate was practically the same irrespective of the portal concentration. For theoretical reasons one would expect progressively longer appearance times when the portal concentration was decreased. It is possible that the amount of flufenamic acid bound to the cell membranes during the early stages of the infusion produced changes that enabled these structures to bind a larger quantity of the drug than originally possible.
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Transport, metabolism and Distribution Space of octanoate in the perfused rat liver.
Cell biochemistry and function, 1997Co-Authors: Osvaldo Ferraresi-filho, Emy Luiza Ishii-iwamoto, Adelar BrachtAbstract:The scope of the present work was to investigate the metabolism and the passage of octanoate from albumin into the phospholipid bilayer of the plasma membrane and from thence into the cell Space. The experiments were done in the isolated perfused rat liver with infusions of albumin and octanoate at various concentrations. Once steady-state conditions were attained, trace amounts of [1-14C]-octanoate, [131 I]-albumin and [3H]-water were injected simultaneously and the effluent perfusate was fractionated. The normalized dilution curves were used for model analysis. The model which gives the best fit to the experimental results and which also produces the most consistent parameters is one that presupposes a rapid Distribution of octanoate into the cell membrane and a slow transfer from the cell membrane into the cytosol. The concentration dependence of the Distribution between the membrane and the extracellular Space is parabolic, suggesting that octanoate changes the properties of the cell membrane when present at higher concentrations. The passage from the cell membrane into the cell Space is relatively slow and limits metabolic transformation partly or totally, depending on the octanoate concentration in the plasma membrane. The rapid transfer of octanoate from the albumin Space into the plasma membrane corroborates previous measurements of the dissociation of the albumin-octanoate complex.
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Transport, Distribution Space and intracellular concentration of the anti- inflammatory drug niflumic acid in the perfused rat liver
Biochemical pharmacology, 1993Co-Authors: Ana Maria Kelmer-bracht, Emy Luiza Ishii-iwamoto, Adelar BrachtAbstract:Transport and Distribution Space of niflumic acid in the perfused rat liver were investigated employing the multiple-indicator dilution technique with constant infusion of the drug (step input). Niflumic acid permeated the cell membrane in both directions at very high rates and its Distribution in the cellular Space was flow-limited; at least at 37 degrees, the rates of influx and efflux could not be measured. Dissociation of the niflumic acid-albumin complex also occurred at very high rates. The apparent Space of Distribution of niflumic acid in the liver depended on the concentration of the drug and varied between 4.37 (1 mM) and 43.5 (10 microM) times the water Space; even with 90% extracellular binding to albumin, the apparent Space of Distribution of niflumic acid was 5.1 times greater than the water Space. The high apparent Spaces of Distribution reflected the high intracellular concentrations. The ratio of intracellular bound plus free concentration to the extracellular bound plus free concentration (Ci/Ce) varied between 6.62 (1 mM portal niflumic acid) and 71.0 (10 microM portal niflumic acid). Metabolic transformation depended on the concentration of the free form. Intracellular binding is probably the major reason for the high concentration of the drug in the hepatic tissue.
Jianzhong Lin - One of the best experts on this subject based on the ideXlab platform.
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hybrid method of moments with interpolation closure taylor series expansion method of moments scheme for solving the smoluchowski coagulation equation
Applied Mathematical Modelling, 2017Co-Authors: Jianzhong LinAbstract:Abstract This paper presents a hybrid method of moments with interpolation closure–Taylor-series expansion method of moments (MoMIC–TEMoM) scheme for solving the Smoluchowski coagulation equation. In the proposed scheme, the exponential function, which arises in the conversion from a particle size Distribution Space to a Space of moments, is expressed in an additive form using the third-order Taylor-series expansion; the implicit moments are approximated using two Lagrange interpolation functions, namely the newly defined normalized moment function and the normalized moment function defined by Frenklach and Harris (1987). The new hybrid scheme allows implementation of the method of moments with an arbitrary type of moment sequence, and it overcomes the shortcomings of the Taylor-series expansion moment method proposed by Frenklach and Harris. The proposed scheme is verified with three aerosol dynamics, namely Brownian coagulation in the free molecular regime, Brownian coagulation in the continuum-slip regime, and turbulence coagulation. The results reveal that the hybrid MoMIC–TEMoM scheme has similar accuracy to currently recognized methods including the quadrature method of moments, MoMIC, and TEMoM, and its accuracy can be further enhanced as the fractional moment sequence type is used for Brownian coagulation in the free molecular regime. Thus, the proposed scheme is a reliable for solving the Smoluchowski coagulation equation.
Mingzhou Yu - One of the best experts on this subject based on the ideXlab platform.
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Hybrid method of moments with interpolation closure–Taylor-series expansion method of moments scheme for solving the Smoluchowski coagulation equation
Applied Mathematical Modelling, 2017Co-Authors: Mingzhou YuAbstract:Abstract This paper presents a hybrid method of moments with interpolation closure–Taylor-series expansion method of moments (MoMIC–TEMoM) scheme for solving the Smoluchowski coagulation equation. In the proposed scheme, the exponential function, which arises in the conversion from a particle size Distribution Space to a Space of moments, is expressed in an additive form using the third-order Taylor-series expansion; the implicit moments are approximated using two Lagrange interpolation functions, namely the newly defined normalized moment function and the normalized moment function defined by Frenklach and Harris (1987). The new hybrid scheme allows implementation of the method of moments with an arbitrary type of moment sequence, and it overcomes the shortcomings of the Taylor-series expansion moment method proposed by Frenklach and Harris. The proposed scheme is verified with three aerosol dynamics, namely Brownian coagulation in the free molecular regime, Brownian coagulation in the continuum-slip regime, and turbulence coagulation. The results reveal that the hybrid MoMIC–TEMoM scheme has similar accuracy to currently recognized methods including the quadrature method of moments, MoMIC, and TEMoM, and its accuracy can be further enhanced as the fractional moment sequence type is used for Brownian coagulation in the free molecular regime. Thus, the proposed scheme is a reliable for solving the Smoluchowski coagulation equation.
Laurent Messonnier - One of the best experts on this subject based on the ideXlab platform.
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Muscle MCT4 Content Is Correlated with the Lactate Removal Ability during Recovery Following All-Out Supramaximal Exercise in Highly-Trained Rowers
Frontiers in Physiology, 2016Co-Authors: Hugo Maciejewski, Muriel Bourdin, Christian Denis, Léonard Feasson, Hervé Dubouchaud, Hubert Freund, Laurent MessonnierAbstract:The purpose of this study was to test if the lactate exchange (³1) and removal (³2) abilities during recovery following short all-out supramaximal exercise correlate with the muscle content of MCT1 and MCT4, the two isoforms of the monocarboxylate transporters family involved in lactate and H+ co-transport in skeletal muscle. Eighteen lightweight rowers completed a 3-min all-out exercise on rowing ergometer. Blood lactate samples were collected during the subsequent passive recovery to assess an individual blood lactate curve (IBLC). IBLC were fitted to the bi-exponential time function: La(t) = [La](0) + A1(1 e³t1) + A2(1 e³t2) where [La](0) is the blood lactate concentration at exercise completion and the velocity constants ³1 and ³2 denote the lactate exchange and removal abilities, respectively. An application of the bi-compartmental model of lactate Distribution Space allowed estimation of the lactate removal rate at exercise completion [LRR(0)]. Biopsy of the right vastus lateralis was taken at rest to measure muscle MCT1 and MCT4 content. Fiber type Distribution, activity of key enzymes and capillary density (CD) were also assessed. ³1 was correlated with [La](0) (r = 0.54, P < 0.05) but not with MCT1, MCT4 or CD. ³2 and LRR(0) were correlated with MCT4 (r = 0.63, P < 0.01 and r = 0.73, P < 0.001, respectively) but not with MCT1 or cytochrome c oxidase activity. These findings suggest that the lactate exchange ability is highly dependent on the milieu so that the importance of the muscle MCT1 and MCT4 content in ³1 was hidden in the present study. Our results also suggest that during recovery following all-out supramaximal exercise in well-trained rowers, MCT4 might play a significant role in the Distribution and delivery of lactate for its subsequent removal.
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Lactate accumulation in response to supramaximal exercise in rowers
Scandinavian Journal of Medicine and Science in Sports, 2013Co-Authors: Hugo Maciejewski, Muriel Bourdin, Jean-rené Lacour, Christian Denis, Bernard Moyen, Laurent MessonnierAbstract:The aim of this study was to test i) three methods to estimate the Quantity of Lactate Accumulated (QLaA) in response to supramaximal exercise and ii) correlations between QLaA and the non-oxidative energy supply assessed by the Accumulated Oxygen Deficit (AOD). Nine rowers performed a 3-min all-out test on a rowing ergometer to estimate AOD and lactate accumulation in response to exercise. Peak blood lactate concentration ([La]peak) during recovery was assessed, allowing QLaA(m1) to be estimated by the method of Margaria et al. Application of a bicompartmental model of lactate Distribution Space to the blood lactate recovery curves allowed estimation of i) the Net Amount of Lactate Released during recovery from the active muscles (NALRmax), and ii) QLaA according to two methods (QLaA(m2) and QLaA(m3)). [La]peak did not correlate with AOD. QLaA(m1), QLaA(m2) and QLaA(m3) correlated with AOD (r = 0.70, r = 0.85 and r = 0.92, respectively). These results confirm that [La]peak does not provide reliable information on non-oxidative energy supply during supramaximal exercise. The correlations between AOD and QLaA(m2) and QLaA(m3) support the concept of studying blood lactate recovery curves to estimate lactate accumulation and thus the contribution of non-oxidative pathway to energy supply during supramaximal exercise.
Hugo Maciejewski - One of the best experts on this subject based on the ideXlab platform.
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Muscle MCT4 Content Is Correlated with the Lactate Removal Ability during Recovery Following All-Out Supramaximal Exercise in Highly-Trained Rowers
Frontiers in Physiology, 2016Co-Authors: Hugo Maciejewski, Muriel Bourdin, Christian Denis, Léonard Feasson, Hervé Dubouchaud, Hubert Freund, Laurent MessonnierAbstract:The purpose of this study was to test if the lactate exchange (³1) and removal (³2) abilities during recovery following short all-out supramaximal exercise correlate with the muscle content of MCT1 and MCT4, the two isoforms of the monocarboxylate transporters family involved in lactate and H+ co-transport in skeletal muscle. Eighteen lightweight rowers completed a 3-min all-out exercise on rowing ergometer. Blood lactate samples were collected during the subsequent passive recovery to assess an individual blood lactate curve (IBLC). IBLC were fitted to the bi-exponential time function: La(t) = [La](0) + A1(1 e³t1) + A2(1 e³t2) where [La](0) is the blood lactate concentration at exercise completion and the velocity constants ³1 and ³2 denote the lactate exchange and removal abilities, respectively. An application of the bi-compartmental model of lactate Distribution Space allowed estimation of the lactate removal rate at exercise completion [LRR(0)]. Biopsy of the right vastus lateralis was taken at rest to measure muscle MCT1 and MCT4 content. Fiber type Distribution, activity of key enzymes and capillary density (CD) were also assessed. ³1 was correlated with [La](0) (r = 0.54, P < 0.05) but not with MCT1, MCT4 or CD. ³2 and LRR(0) were correlated with MCT4 (r = 0.63, P < 0.01 and r = 0.73, P < 0.001, respectively) but not with MCT1 or cytochrome c oxidase activity. These findings suggest that the lactate exchange ability is highly dependent on the milieu so that the importance of the muscle MCT1 and MCT4 content in ³1 was hidden in the present study. Our results also suggest that during recovery following all-out supramaximal exercise in well-trained rowers, MCT4 might play a significant role in the Distribution and delivery of lactate for its subsequent removal.
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Lactate accumulation in response to supramaximal exercise in rowers
Scandinavian Journal of Medicine and Science in Sports, 2013Co-Authors: Hugo Maciejewski, Muriel Bourdin, Jean-rené Lacour, Christian Denis, Bernard Moyen, Laurent MessonnierAbstract:The aim of this study was to test i) three methods to estimate the Quantity of Lactate Accumulated (QLaA) in response to supramaximal exercise and ii) correlations between QLaA and the non-oxidative energy supply assessed by the Accumulated Oxygen Deficit (AOD). Nine rowers performed a 3-min all-out test on a rowing ergometer to estimate AOD and lactate accumulation in response to exercise. Peak blood lactate concentration ([La]peak) during recovery was assessed, allowing QLaA(m1) to be estimated by the method of Margaria et al. Application of a bicompartmental model of lactate Distribution Space to the blood lactate recovery curves allowed estimation of i) the Net Amount of Lactate Released during recovery from the active muscles (NALRmax), and ii) QLaA according to two methods (QLaA(m2) and QLaA(m3)). [La]peak did not correlate with AOD. QLaA(m1), QLaA(m2) and QLaA(m3) correlated with AOD (r = 0.70, r = 0.85 and r = 0.92, respectively). These results confirm that [La]peak does not provide reliable information on non-oxidative energy supply during supramaximal exercise. The correlations between AOD and QLaA(m2) and QLaA(m3) support the concept of studying blood lactate recovery curves to estimate lactate accumulation and thus the contribution of non-oxidative pathway to energy supply during supramaximal exercise.