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A Llebaria

Publications and source records attributed to A Llebaria.

10 recordsLinked to original sources
PubMed2002

High-performance liquid chromatography with electrochemical detection applied to the analysis of 3,4-dihydroxymethamphetamine in human plasma and urine.

Metabolic activation in the disposition of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") has been implicated in some of its pharmacological and toxicological effects, with the major metabolite 3,4-dihydroxymethamphetamine (HHMA) as a putative toxicant through the formation of thioether adducts. We describe the first validated method for HHMA determination based on acid hydrolysis of plasma and urine samples, further extraction by a solid-phase strong cation-exchange resin (SCX, benzenesulfonic acid), and analysis of extracts by high-performance liquid chromatography with electrochemical detection. The chromatographic separation was performed in an n-butyl-silane (C4) column and the mobile phase was a mixture of 0.1 M sodium acetate containing 0.1 M 1-octanesulphonic acid and 4 mM EDTA (pH 3.1) and acetonitrile (82:18, v/v). Compounds were monitored with an electrochemical cell (working potentials 1 and 2, +0.05 and +0.35 V, respectively, gain 60 microA). A mobile phase conditioning cell with a potential set at +0.40 V was connected between the pumping system and the injector. Calibration curves were linear within the working concentration ranges of 50-1000 microg/L for urine and plasma. Limits of detection and quantification were 10.5 and 31.8 microg/L for urine and 9.2 and 28.2 microg/L for plasma. Recoveries for HHMA and DHBA (3,4-dihydroxybenzylamine, internal standard) were close to 50% for both biological matrices. Intermediate precision and inter-day accuracy were within 3.9-6.5% and 7.4-15.3% for urine and 5.0-10.8% and 9.2-13.4% for plasma.

Calibration↗
PubMed2001

3,4-Dihydroxymethamphetamine (HHMA). A major in vivo 3,4-methylenedioxymethamphetamine (MDMA) metabolite in humans.

There is evidence that some heavy users of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) show signs of neurotoxicity (a cognitive dysfunction, a larger incidence of psychopathology). It has been postulated that the catechol intermediates of methylenedioxyamphetamines such as 3,4-dihydroxymethamphetamine (HHMA), a metabolite of MDMA, may play a role in their neurotoxicity by formation of thioether adducts. This study describes the first validated method for HHMA determination in plasma and urine by strong cation-exchange solid-phase extraction high-performance liquid chromatography/electrochemical detection (HPLC/ED) analysis. The method has been applied for the determination of HHMA in plasma and urine samples from a clinical study in healthy volunteers of MDMA and provides preliminary kinetic data on this metabolite. HHMA appeared to be a major MDMA metabolite with plasma concentrations as high as the parent compound. Thus, HHMA C(max) (154.5 microg/L) and AUC(0-24h)(1990.9 microg/L h) were similar to those obtained in previously published reports for MDMA (181.6 microg/L and 1465.9 microg/L h, respectively). The 24-h urinary recovery of HHMA accounted for 17.7% of the MDMA dose administered and increases the total 24 h recovery of MDMA and metabolites to 58% of the 100 mg dose administered. The determination of HHMA in plasma and urine samples is of interest in order to establish its relevance in MDMA metabolism and its possible contribution to MDMA neurotoxicity in humans. Its validation showed appropriate accuracy and precision for its use in pharmacokinetic studies.

Adult↗
PubMed1989

Molecular organization and clustering of cell-wall-bound enzymes as a source of kinetic apparent co-operativity.

When fixed charges and enzyme molecules are not homogeneously distributed in a matrix, the degree of organization of charges, of enzyme molecules and of charges with respect to enzyme molecules modulate the enzyme reaction rate. The overall reaction velocity of the bound enzyme system may be expressed in terms of monovariate moments of the charge density distribution and of the bivariate moments of the charge and enzyme density distributions. With respect to the situation where fixed charges and enzyme molecules are randomly distributed in the matrix, the molecular organization, as expressed by the monovariate and bivariate moments results in an increase or a decrease, of the overall reaction rate, as well as in the appearance of a kinetic cooperativity. The degree of spatial organization of objects may be expressed quantitatively through the concept of minimal spanning tree. This concept may thus be applied to the quantification of the degree of order that may exist in the bidimensional distribution of enzyme molecules in a charged matrix. Primary walls of isolated plant cells in sterile culture behave as a polyanion and contain different enzymes. The spatial distribution in sycamore cell walls of an acid phosphatase has been studied through the concept of minimal spanning tree and shown to be non-randomly distributed in the polyanionic matrix, but clustered in that matrix. This spatial organization results in a modulation of the reaction rate of the cell-wall-bound phosphatase reaction. Both the theoretical and experimental results presented in this study leave little doubt as to the validity of the idea that in situ the organization of fixed charges and enzyme molecules modulate the overall dynamics of enzyme reactions.

Acid Phosphatase↗
PubMed1989

Toward a new approach in tumor cell heterogeneity studies using the concept of order.

A new methodology was developed to study dynamic processes topographically in biological systems by means of a graph-theoretical method. It is based upon order parameters obtained from a minimal spanning tree analysis coupled with computer simulations. The method was used to analyse the heterogeneous behavior of two neoplastic cell lines after treatment with laminin. The laminin-induced cell detachment was quantitated and shown to be inversely related to cell population density and thus to cellular interactions. Our statistical analysis is a very powerful tool to obtain information from seemingly disorderly heterogeneous biological models.

Animals↗
PubMed1988

Quantization of directional properties in biological structures using the Minimal Spanning Tree.

A method that uses the Minimal Spanning Tree graph has previously been developed (Dussert et al., 1987, J. theor. Biol. 125, 317) in order to analyse the degree of order in biological structures. This graph is shown here to be very powerful in bringing out directional properties of biological structures which cannot be revealed by a simple visual examination. The method is illustrated by means of various computer simulations.

Computer Simulation↗
PubMed1987

Minimal spanning tree analysis of biological structures.

A new approach to study order and disorder in biological membranes and more generally in biological structures is developed. It is based on a graph constructed on the set points representing the position of particles. From this graph, which is called the minimal spanning tree, it is possible to deduce two parameters, namely the average length m and the standard deviation sigma which are characteristic of the repartition to be studied. The use of a diagram involving both m and sigma makes it possible to determine the degree of order by taking a simple reading in the (m, sigma) plane.

Cell Membrane↗
PubMed1985

Quantitative characterization of a biological membrane by means of its spatial autocovariance.

Profiles for the exoplasmic face (EF) of the freeze-fractured plasma membrane from the root storage tissue of red beets are reconstructed by microdensitometry of micrographs of surface-shadowed-platinum carbon replicas. Autocovariance functions (ACFs) are computed from those profiles. The initial portions of the ACFs have a Gaussian form whose parameters (root mean square surface roughness and autocovariance length) are estimated. The parameter estimates are used to show that the pits on the EF faces are in good complementarity with the intramembrane particles seen on the complementary protoplasmic fracture faces.

Cell Membrane↗