Explosives: a microsensor for trinitrotoluene vapour.
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Journal Article↗
Biomedical subjects
G Muralidharan
Publications and source records attributed to G Muralidharan.
An atomic force microscope-based investigation of vertical transport through GaAs/GaAlAs/InAlAs/GaAs step-barrier heterostructures.
Study of vertical transport through heterostructures consisting of single, double, or multiple quantum barriers is of both fundamental and technological interest. While extensive data regarding electron transport is available for single- and double-barrier structures, relatively less information is available for transport through step-barrier structures. In this paper, we present results from a study of room temperature vertical transport through a GaAs/GaAlAs/InAlAs/GaAs multistep-barrier heterostructure. A typical atomic force microscope has been adapted to perform transport measurements, thus allowing precise control of the physical location of the region of measurement. I-V measurements reveal negative differential resistance (NDR) peaks, thus confirming the formation of resonant states in a triangular well created when a voltage bias is applied across the step barrier. I-V curves have also been calculated by numerically solving the Schrödinger wave equation for this step-barrier structure. Comparison between the measured and calculated I-V curves shows reasonable agreement in the number of NDR peaks. However, discrepancies exist between the measured and calculated values for the voltages at which these NDR peaks occur. Some possible reasons for these discrepancies are discussed in this work.
Journal Article↗
Quinidine inhibits the 7-hydroxylation of chlorpromazine in extensive metabolisers of debrisoquine.
Quindine is a potent inhibitor of CYP2D6 (debrisoquine 4-hydroxylase). Its effect on the disposition of chlorpromazine was investigated in ten healthy volunteers using a randomised crossover design with two phases. A single oral dose of chlorpromazine hydrochloride (100 mg) was given with and without prior administration of quinidine bisulphate (250 mg). Chlorpromazine and seven of its metabolites were quantified in the 0- to 12-h urine while plasma concentrations of chlorpromazine and 7-hydroxychlorpromazine were measured over 48 h. All volunteers were phenotyped as extensive metabolisers with respect to CYP2D6 using the methoxyphenamine/O-desmethyl-methoxyphenamine metabolic ratio. Quinidine significantly decreased the urinary excretion of 7-hydroxylchlorpromazine 2.2-fold. Moreover the urinary excretion of this metabolite correlated inversely (rs = -0.80) with the metabolic ratio. The urinary recoveries of chlorpromazine, chlorpromazine N-oxide, 7-hydroxy-N-desmethylchlorpromazine, N-desmethyl-chlorpromazine sulphoxide and the total of all eight analytes were unaltered by quinidine. However, quinidine administration caused significant increases in the urinary excretions of chlorpromazine sulphoxide, N-desmethylchlorpromazine and N, N-didesmethylchlorpromazine sulphoxide, which indicated that compensatory increase in these metabolic routes of chlorpromazine might have been responsible for the lack of change observed in the urinary recovery of the parent drug. Quinidine administration produced modest decreases (1.2- to 1.3-fold) in the mean peak plasma concentrations and mean areas under the plasma concentration-time curves of 7-hydroxychlorpromazine and increases (1.3- to 1.4-fold) in these parameters for the parent drug chlorpromazine, but none of these changes reached statistical significance. Based on ANOVA the sample sizes required to detect these differences as significant (alpha = 0.5) with a probability of 0.8 were determined to vary between 15 and 42. These data suggest that CYP2D6 is involved in the metabolism of chlorpromazine to 7-hydroxychlorpromazine. However, genetic polymorphism in this metabolic process did not play a dominant role in accounting for the extremely large interindividual variations in plasma concentrations encountered with this drug.
Adult↗
Quinidine but not quinine inhibits in man the oxidative metabolic routes of methoxyphenamine which involve debrisoquine 4-hydroxylase.
Healthy male volunteers (n = 13) took a single oral dose of 60.3 mg of methoxyphenamine HCl with and without prior administration of either quinidine (250 mg as bisulphate salt) or its diastereomer quinine (300 mg as sulphate salt). Methoxyphenamine and its N-desmethyl, O-desmethyl and aromatic 5-hydroxy metabolites were quantified in the 0-32 h urine. The oxidative routes of methoxyphenamine metabolisms which had been previously shown to involve debrisoquine 4-hydroxylase, namely O-demethylation and 5-hydroxylation were both significantly inhibited by quinidine in the 12 extensive metabolizers. The inhibition was selective in that N-demethylation which does not involve this isozyme was not affected by quinidine. In all but one of these volunteers the methoxyphenamine/O-desmethylmethoxyphenamine ratio changed such that extensive metabolizers could be classified as poor metabolizers due to quinidine pretreatment. No marked change occurred in the renal excretion of methoxyphenamine and its three metabolites either in the extensive metabolizers because of quinine pretreatment or in the poor metabolizer because of treatment with either quinidine or quinine. Thus in the extensive metabolizer phenotype it was demonstrated in one study that enzyme inhibition of quinidine was selective in terms of the metabolic pathways inhibited as well as stereoselective with respect to the inhibitor.
Adult↗
Quinine is a more potent inhibitor than quinidine in rat of the oxidative metabolic routes of methoxyphenamine which involve debrisoquine 4-hydroxylase.
1. Lewis rats (n = 7 or 8) were dosed with methoxyphenamine with and without prior administration of various doses of either quinine or its diastereomer quinidine. Methoxyphenamine and its N-desmethyl, O-desmethyl and aromatic 5-hydroxy metabolites were quantified in 0-24 h urine. 2. The oxidative routes of methoxyphenamine metabolism which had been previously shown to involve the debrisoquine/sparteine isoenzyme, namely O-demethylation and 5-hydroxylation, were both significantly inhibited by quinine. The inhibition was selective in that N-demethylation which does not involve this isoenzyme was not affected by quinine. 3. Quinidine which had been previously shown at a relatively high dose (80 mg/kg) to affect the three metabolic routes of methoxyphenamine in a similar fashion was ineffective in this regard at a 25 mg/kg dose. Quinine more effectively inhibited the O-demethylation and 5-hydroxylation of methoxyphenamine than did quinidine, and its inhibition was marked at the lowest dose examined, 12.5 mg/kg. 4. As quinidine is a more potent inhibitor than quinine of debrisoquine 4-hydroxylase in man, the rat should be used only with full realization of its limitations when investigating substrates metabolized by this isoenzyme.
Animals↗
Selective in vivo inhibition by quinidine of methoxyphenamine oxidation in rat models of human debrisoquine polymorphism.
1. Lewis and Dark Agouti (DA) rat strains (n = 4), models of human extensive and poor metabolizer phenotypes of debrisoquine/sparteine, respectively, were dosed with methoxyphenamine with and without prior administration of quinidine. Methoxyphenamine and its three metabolites, namely N-desmethylmethoxyphenamine, O-desmethylmethoxyphenamine and 5-hydroxymethoxyphenamine were quantified in 0-24 h urine. 2. The oxidative metabolic routes of methoxyphenamine which had been previously shown to involve the debrisoquine/sparteine isozyme, namely O-demethylation and aromatic 5-hydroxylation, were both significantly inhibited by quinidine in the two rat strains. 3. The oxidative metabolic route of methoxyphenamine which had been previously shown to not involve the debrisoquine/sparteine isozyme, namely N-demethylation, was not significantly inhibited by quinidine in either rat strain. 4. The Lewis strain pretreated with quinidine resembled the DA strain without such pretreatment in terms of O-desmethylmethoxyphenamine and 5-hydroxymethoxyphenamine in that the mean percentages of the dose excreted as these two metabolites and the mean O-desmethylmethoxyphenamine/methoxyphenamine and 5-hydroxymethoxyphenamine/methoxyphenamine ratios were similar to one another. 5. Ten days after quinidine administration to the Lewis strain of rat, all parameters of methoxyphenamine and its metabolites returned to normal. 6. A protocol involving substrate administration to Lewis strain rats with and without prior administration of quinidine could be developed as an attractive approach to screen substrates for metabolism in vivo by the debrisoquine/sparteine isozyme. Such an approach obviates interstrain differences.
Amphetamines↗
Manipulation of microcantilever oscillations.
Experimental observation of self-sustaining oscillations via a delayed feedback system is presented for a rectangular silicon microcantilever. The system is modeled as one and two-dimensional damped oscillator and the resulting delay differential equations are studied in frequency and time domain. The shortcomings of each model are outlined, and an improved formulation of the dynamics of the cantilever is presented.
Journal Article↗
Adsorption-desorption characteristics of explosive vapors investigated with microcantilevers.
Understanding the kinetics of adsorption and desorption of explosive vapors such as TNT from surfaces is important in the design of sensors. We report for the first time, the adsorption-desorption characteristics of TNT from a Si-microcantilever exposed to vapors of TNT. It was observed that TNT readily sticks to the exposed Si surface with the adsorption kinetics showing an initial exponential behavior followed by roughly linear kinetics. It was also observed that for cantilever temperatures close to room temperature, TNT desorbs spontaneously from the surface with decaying exponential kinetics. Based on the known equilibrium partial vapor pressures of TNT, the "effective" sticking coefficient for the silicon oxide surface at room temperature under the experimental conditions was calculated to be about 0.02. This information can be very useful in the design of sensors and that of vapor-delivery systems.
Journal Article↗
Covalent attachment of gold nanoparticles to DNA templates.
Functionalized gold nanoparticles have been covalently bound to internal, modified sites on double-stranded DNA. Gold nanoparticles coated with mercaptosuccinic acid or thioctic acid were bound to amino-modified thymine bases on double-stranded DNA. Visible absorption spectra, gel electrophoresis, and atomic force microscopy were used to analyze the products. Thiol groups were added to one end of the gold/nanoparticle product, which was then attached to a gold surface. This method has the potential to allow controlled placement of particles with subnanometer precision and to allow attachment of the product to fixed contacts for nanodevice fabrication.
Binding Sites↗