Search PubMed⌕ Search

Biomedical subjects

W J Albery

Publications and source records attributed to W J Albery.

At least 37 records · Page 2Linked to original sources

The effect of unilateral cortical lesions on the circadian changes in rat striatal ascorbate and homovanillic acid levels measured in vivo using voltammetry.

Linear sweep voltammograms were recorded in the striata of rats with a unilateral cortical lesion. The height of the ascorbate peak was 55% smaller on the lesioned side compared with the intact side, the homovanillic acid peak showed no significant change. The nocturnal increase in the release of striatal ascorbate was reduced by 80% on the lesioned side whilst the circadian variation in homovanillic acid was unaffected. These results support the hypothesis that there is a link between glutamate release and extracellular ascorbate concentrations in the brain.

Animals↗

The compartment model for chronically implanted voltammetric electrodes in the rat brain.

Experimental properties of the peaks obtained with carbon paste electrodes and microprocessor-based linear sweep voltammetry in the rat brain have been compared with those predicted by a theoretical treatment of the problem which we have recently developed. This comparison indicates that the electrodes are situated in a restricted compartment and that the oxidation of ascorbate under these conditions is irreversible. Examples of how this situation has been exploited to improve the voltammograms obtained are given.

Animals↗

The development of linear sweep voltammetry with carbon paste electrodes in vivo.

A number of advances have been made in the application of linear sweep voltammetry with carbon paste electrodes to the monitoring of ascorbate and monoamine neuroregulator metabolites in the brain of the freely-moving rat. These new measures are: the reduction of the sweep rate of 5 mV/s; the elimination of semidifferentiation in chronic recordings; the measurement in situ and subtraction of the background current for each electrode; the reduction, to practically zero levels, of the ascorbate signal in alternate scans; and corrections for circadian changes. These innovations enable one to monitor changes in the monoamine metabolites, even when there are simultaneous, large changes in ascorbate.

Animals↗

The monitoring of ascorbate and monoamine transmitter metabolites in the striatum of unanaesthetised rats using microprocessor-based voltammetry.

Voltammetry in vivo has suffered from the limitation that electrodes which give high resolution of the various electroactive compounds present in brain tissue have a short life span, and, conversely, that stable electrodes give poor resolution. Carbon paste electrodes and linear sweep voltammetry with semidifferentiation can resolve changes in the concentration of ascorbate, deaminated and methylated metabolites of catecholamines, and the 5-hydroxyindoles in vivo and give stable recordings over many weeks. However, these changes in concentration are difficult to quantify. We have now developed the method further with the application of microprocessor technology. Microprocessor-based voltammetry and data analysis enable one to quantify changes in the concentration of electroactive species in complex mixtures where there are no separate oxidation peaks for the components; this has been achieved both in vitro and in vivo. Changes in dopamine release from the striatum have been monitored continuously over 48 h in unanaesthetised rats after the intraperitoneal administration of haloperidol. Carbon paste electrodes and microprocessor-controlled linear sweep voltammetry facilitates the quantitative, continuous monitoring of the extracellular concentration of ascorbate, the deaminated and methylated metabolites of catecholamines, and the 5-hydroxyindoles in the brain of unrestrained animals.

3,4-Dihydroxyphenylacetic Acid↗

Circadian changes in homovanillic acid and ascorbate levels in the rat striatum using microprocessor-controlled voltammetry.

Circadian variations in the extracellular concentration of ascorbate and homovanillic acid in the striatum of unrestrained rats were measured simultaneously at 12 min intervals over periods of up to 48 h using carbon paste electrodes and microprocessor-controlled linear sweep voltammetry. Both compounds show a similar time course over a 24 h period, reaching a peak at 04.00 h and falling to a minimum at around 16.00 h. The changes in homovanillic acid probably reflect changes in dopamine release associated with circadian variations in the level of motor activity, while the origin and function of the ascorbate changes are unknown.

Animals↗

Linear sweep voltammetry with carbon paste electrodes in the rat striatum.

Voltammetry has been widely used in attempts to measure catecholamine release in vivo. The voltammogram recorded in the rat striatum using carbon paste electrodes and linear sweep voltammetry with semidifferentiation consists of a number of separate peaks; changes in the height of the first of these peaks have been attributed to changes in catecholamine release. We have found that ascorbate, either microinjected into the striatum or injected intraperitoneally, increases the height of the first peak without changing its potential. Microinjection of dopamine or 3,4-dihydroxyphenylacetic acid, or intraperitoneal injection of 3,4-dihydroxyphenylalanine, caused a shift in the potential of peak 1 of 25-50 mV in a positive direction. Amphetamine, administered intraperitoneally to freely moving animals, caused an increase in the height of the first peak but did not change its potential. Oxidation potentials in vitro and the effect of other drugs on the voltammogram obtained in vivo were also measured. Peak 1 is caused by the oxidation of both ascorbate and catechols whose oxidation potentials differ by only 50 mV in vivo; the contribution of catechols in control animals is negligible. Shifts in the potential of peak 1 caused by drugs are not due to changes in the oxidation potentials of the components but to a change in their relative contributions. Therefore changes in the height of peak 1 with no change in position do not represent changes in the extracellular concentration of catechols but are due to changes in ascorbate concentration. Changes in the concentration of catecholamine-related compounds can be detected at potentials some 50 mV greater than that of the first peak.

Animals↗

A sandwich electrode for multi-gas analysis: a prototype.

A prototype composite electrode consisting of a metallized membrane "outer" cathode, and a conventional "inner" silver disc cathode, both sharing the same electrolyte, is described. Preliminary results indicate that the metallized membrane will act as an oxygen filter, allowing anaesthetic gases such as nitrous oxide, to pass through to the second (inner) cathode, where they may be reduced. Linear relationships exist for oxygen concentration and metallized membrane current; and for nitrous oxide concentration and the second cathodic current. Extension of this technique to measure both halothane and nitrous oxide on the second cathode, simultaneously with oxygen on the metallized membrane, is discussed.

Electrodes↗

The polarographic measurement of halothane.

The polarographic reduction of halothane on silver cathodes was studied. Silver catalyses the reduction of halothane: two electrons are exchanged in the reduction process. Experiments using a rotating disc electrode showed a linear relationship between observed current and halothane concentration. A Silastic membrane-covered polarographic electrode was constructed using a silver cathode which gave a good linear response to changes in halothane concentration over the range 0.5% v/v halothane in nitrogen. Oxygen interferes with the measurement of halothane, but can be removed from a gas sample before analysis.

Electrodes↗

On-line PO2 and PN2O analysis with an in vivo catheter electrode.

A technique was developed for the in vivo determination of PO2 and PN2O with a catheter electrode using double-pulse polarography. The method was evaluated in dog studies comparing readings from the electrode with those from a mass spectrometer employing an in vivo probe. The oxygen readings obtained from the catheter electrode were also compared with values obtained by conventional blood-gas analysis. Good agreement was observed between the electrode and the mass spectrometer for both PO2 and PN2O. Similar agreement was found between the electrode readings and blood-gas analysis for PO2. In the presence of halothane, the electrode over-read for both PO2 and PN2O; a remedy is suggested. The in vivo electrode provides an effective, less expensive, alternative to the mass spectrometer for the on-line measurement of PO2 and PN2O in vivo.

Animals↗

O2 and N2O analysis with a single intravascular catheter electrode. An in-vitro study.

The simultaneous measurement of O2 and N2O in liquid, using a single polarographic catheter electrode, is described. It is shown that commercial PO2 intravascular electrodes, with silver cathodes, produce separate and distinct polarograms for O2 and N2O, and that these electrodes can be used for the measurement of both PO2 and PN2O.

Blood Gas Analysis↗

Percutaneous absorption: interfacial transfer kinetics.

A new rotating diffusion cell is described in which a solute diffuses through a rotating filter. The transport of the solute to both sides of the filter is controlled by the rotation. The filter is filled with an organic phase. The rate of transfer of the solute through the filter is determined by the transport and by the kinetics of the interfacial transfer reactions. Since the transport is controlled the rate constant for the transfer reaction can be measured. Results for eleven different systems are reported and it is found that the rate constants are all smaller than 10(-4) ms-1.

Diffusion↗

Percutaneous absorption: theoretical description.

Equations are derived to describe the percutaneous absorption of a substance through the epidermal barrier. The treatment includes interfacial barriers and allows for the depletion of the substance in the external phase. The equations are derived both for the continuous application and for pulse experiments where the drug is applied for a time, then removed, and the response occurs some time after the removal of the drug. Competition between the drug diffusing through the keratinized cells (transcellular route) and diffusing in the interstitial channels around the cells (intercellular route) is also considered.

Kinetics↗

Percutaneous absorption: in vivo experiments.

The percutaneous absorption of esters of nicotinic acid has been studied in vivo in man. The time for erythema to be produced has been measured both when the ester is applied continuously and in 'pulse' experiments when the ester is removed before the erythema develops. The results show that the erythema is produced long before steady state diffusion across the epidermis is established and the penetration of methyl nicotinate is characterized by D/l2 = 2.3 X 10(-4)s-1 where D is the diffusion coefficient and l the thickness of the barrier. Results using glycerol water mixtures in the external phase show that the route of penetration for methyl nicotinate is through the interstitial channels and not through the keratinized cells. Data for absorption from various creams and ointments (Barrett et al 1964) show that the route is independent of the nature of the external phase. Steady state data for the absorption of salicylic acid and carbinoxamine through the abdominal skin of guinea-pigs (Arita et al 1970) show that the route of penetration does not change as the experiment proceeds. Data for the absorption of other substances (Michaels et al 1975) also fit the interstitial route.

Diffusion↗

An electrode for PN2O and PO2 analysis in blood and gas.

The development of a new polarographic sensor for measuring simultaneously both N2O and O2, in either gas or blood, is described. The cathode is made of silver, and it is shown that silver deposition on normal platinum or gold cathode electrodes can result in an enhancement of a PO2 signal, when measured in the presence of nitrous oxide. Silver can be deposited on the cathode by means of Ag+ ions diffusing through the electrolyte from an Ag/AgCl reference electrode. The use of an Ag cathode enables both O2 and N2O signals to be measured.

Blood Gas Analysis↗

Deuterium and tritium exchange in enzyme kinetics.

The theory of the isotopic exchange of deuterium and tritium between an enzyme-substrate complex and the solvent is derived for 16 different types of experiment involving measurements of initial velocities and of the isotopic content of the reactants and products as a function of the extent of reaction. It is shown how the data from these experiments can be analyzed to obtain the rate constants for the individual steps and thereby the Gibbs free energies of the intermediates and transition states in the reaction. The effects of isotopic substitution on each intermidiate and transition state are also found and this allows conclusions to be drawn as to the extent to which a proton is in flight in a particular transition state. Neither substrate handling (that is, on-off steps), nor the isotopic exchange with the solvent, is assumed to be rapid.

Deuterium↗

Energetics of triosephosphate isomerase: the appearance of solvent tritium in substrate dihydroxyacetone phosphate and in product.

When the isomerization of dihydroxyacetone phosphate to D-glyceraldehyde 3-phosphate is catalyzed by triosephosphate isomerase in tritiated water, both the substrate and product become labeled. The specific radioactivity of the product is about 80% that of the solvent, which shows that the protonation of the enediol intermediate at C-2 (to form the enzyme-bound product D-glceraldehyde 3-phosphate) is followed by a slower step not involving proton transfer. The specific radioactivity of the remaining substrate after partial reaction rises as the reaction proceeds and shows that the reaction intermediate that exchanges protons with the medium returns to dihydroxyacetone phosphate (picking up tritium) about one-third as often as it is converted to D-glceraldehyde 3-phosphate. These results allow a qualitative description of the relative heights of the energy barriers in the catalyzed reaction and contribute to the quantitative analysis of the energetics of the process.

Carbohydrate Epimerases↗