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Biomedical subjects

M E Rice

Publications and source records attributed to M E Rice.

At least 73 records · Page 4Linked to original sources

Measurement of nanomolar dopamine diffusion using low-noise perfluorinated ionomer coated carbon fiber microelectrodes and high-speed cyclic voltammetry.

Several improvements in the fabrication and use of carbon fiber voltammetric microelectrodes (CFVMs) are described. These procedures did not involve oxidative treatment, but resulted in sensitivities and selectivities approaching those of treated CFVMs, without the inherent slow response times associated with the latter electrodes. To accomplish this we reduced CFVM noise by (1) improving the adhesive seal between the 8 microns o.d. carbon fiber and the glass insulation using vacuum, (2) snapping rather than cutting or beveling the fiber to be flush with the glass, and (3) using a concentrated electrolyte solution to make electrical contact with the fiber. System noise was reduced by digital smoothing and signal averaging. Selectivity of the CFVMs for dopamine over ascorbate was enhanced to better than 2000:1 by coating with Naflon, a perfluorinated cation exchange polymer, using a low (+0.5 V vs Ag/AgCl) electroplating potential. This low voltage also prevented electrode surface oxidation. To demonstrate the performance of our CFVMs, we used them in conjunction with high-speed cyclic voltammetry to accurately measure the diffusion coefficient of iontophoretically released dopamine at concentrations as low as 35 nM over distances of less than 200 microns in agarose gel.

Diffusion↗

Quisqualate, kainate and NMDA can initiate spreading depression in the turtle cerebellum.

This study evaluated the role of excitatory amino acid (EAA) receptor activation in spreading depression (SD), using the in vitro turtle cerebellum as a model system. SD was triggered by electrical stimulation or by elevated K+ after the cerebellum had been conditioned for at least 30 min with physiological saline in which most of the chloride had been replaced by propionate. SD was recognized as a transient (1-3 min) negative shift of extracellular potential accompanied by depression of evoked potentials (15-30 min) and an increase of extracellular K+ up to 60 mM, which spread across the cerebellum at rates of 1-7 mm/min. SD usually commenced in the granular layer, which apparently contains the 3 major EAA receptor subtypes, quisqualate, kainate and N-methyl-D-aspartate (NMDA), then subsequently spread to the molecular layer, which is largely free of NMDA receptors. Glutamate, aspartate, NMDA, kainate and quisqualate all triggered SD. Kynurenic acid and 2-aminophosphonovaleric acid (APV) inhibited SD under certain conditions further suggesting involvement of EAA receptors. The initiation of SD was blocked by high Mg2+ and facilitated in low extracellular Mg2+, which also eliminated the delay in molecular layer SD onset. Our data suggest that no one EAA receptor subtype is singly responsible for SD.

2-Amino-5-phosphonovalerate↗

Behavior of extracellular K+ and pH in skate (Raja erinacea) cerebellum.

Ion-selective microelectrodes were used to measure extracellular K+ concentrations ([K+]o) and extracellular pH (pHo) in skate cerebellum under resting and stimulated conditions. Consistent with earlier ion analysis of elasmobranch cerebrospinal fluid (CSF), [K+]o was 3.6 +/- 0.1 mM. During parallel fiber activation, [K+]o increased to an upper limit of 12-14 mM with an approximately linear dependence on stimulation frequency (1-20 Hz). Post-stimulus undershoots of 0.1-0.6 mM were seen throughout an animal temperature range of 13-18 degrees C. When stimulation produced spreading depression (SD), [K+]o first increased to about 10 mM, then rose more rapidly to about 30 mM. These observations indicate a K+ ceiling of 10-12 mM in elasmobranchs. This ceiling is the same as that seen in mammals, despite marked differences in CSF composition and osmolality between mammalian and elasmobranch species. Extracellular pH (resting pHo was 7.1-7.3) was also altered during parallel fiber stimulation. An initial alkaline shift and subsequent extracellular acidification were characteristic of the response. These pHo transients were similar to those reported in other preparations, although the alkaline shift was enhanced. This may be attributed to the relatively low buffering capacity of elasmobranch CSF and to summation with a generally smaller acid shift.

Action Potentials↗

Interstitial ascorbate in turtle brain is modulated by release and extracellular volume change.

The isolated turtle cerebellum was used as a model system to study effects of depolarizing conditions on interstitial ascorbic acid concentration. The depolarizing stimulus was Leão's spreading depression, which is characterized by transient negative extracellular potentials, high potassium levels (20-60 mM), and local depression of neuronal activity. Interstitial concentrations of ascorbate (200-400 microM) and other electroactive species were monitored voltammetrically, using graphite fiber microelectrodes. Total tissue ascorbate (1,810 nmol/g tissue wet weight) was similar to mammalian levels and was several orders of magnitude higher than catecholamine and indoleamine content. During spreading depression, a large (up to 200 microM) increase in concentration of interstitial electroactive species was monitored. Use of Nafion- and ascorbate oxidase-coated electrodes and uricase confirmed that ascorbate was the only substance detected. Simultaneous monitoring of ascorbate, extracellular potential, and extracellular volume (using tetramethylammonium and ion-selective microelectrodes) indicated that (a) the ascorbate increase began with the decrease in extracellular volume during spreading depression, and (b) much of the increase was the result of extracellular volume decrease. In sucrose-substituted medium, in which volume changes are eliminated, a 50 microM increase in interstitial ascorbate, caused by release from intracellular stores, was also seen. The ascorbate concentration increase was prolonged in sucrose medium, suggesting that an uptake process involving sodium may further regulate interstitial ascorbate concentration.

Animals↗

Calcium diffusion in the brain cell microenvironment.

A review of some of the literature on Ca2+ diffusion in free media and a variety of nervous tissues is presented. In the majority of tissue studies the apparent diffusion coefficient of Ca2+ is three to nine times smaller than that in a free aqueous medium. The methodology of using pressure microejection and Ca2+ ion-selective microelectrodes to measure Ca2+ diffusion is discussed. Our ongoing studies of Ca2+ diffusion in the cerebral cortex of the rat, using these methods, also confirm that Ca2+ diffusion is mainly influenced by the tortuosity of the tissue rather than other factors such as binding to extracellular charge sites or uptake.

Animals↗

Medium- and maximum-security units for psychiatric patients in Ontario.

A brief history of the development of a three-level system of security within the Ontario psychiatric hospital system is followed by a presentation of data regarding the maximum- and medium-security units and the patients in those units in 1984. A large proportion of the beds were occupied by patients held on Warrants of the Lieutenant Governor (WLGs). A review of the number of persons held on WLGs both in the province as a whole and in the medium- and maximum-security units over the past several years suggest that there will be an increased demand on these units for beds for WLGs in the future. The characteristic of medium- and maximum-security units are discussed and programs and program needs, are summarized.

Forensic Psychiatry↗

Simultaneous voltammetric and chemical monitoring of dopamine release in situ.

The validity of voltammetric monitoring of stimulated dopamine (DA) release was tested by simultaneous chemical assay of the extracellular fluid region next to the tip of a selective Nafion-coated graphite voltammetric electrode. Micro alumina probes were positioned next to the recording electrode tip to adsorb released catecholamines. The catecholamines were desorbed into microvolumes of acid and analyzed by very sensitive HPLC assays to provide unequivocal chemical verification of the electrochemical signals. The results fully confirm that selective voltammetric electrodes can detect released DA and that the concentrations determined voltammetrically or chemically agree well.

Animals↗

Crisis prevention and intervention training for psychiatric hospital staff.

A 5-day course designed to train psychiatric hospital staff verbal and physical methods of preventing violence and injury when dealing with upset patients was taught to 89 staff from maximum and less secure wards. Compared to no-treatment controls, experimental subjects improved significantly on four tests of crisis-related tests and knowledge. Questionnaire and self-report measures from staff and patients on the training wards also indicated positive course effects. Assault frequencies decreased immediately after the course and staff injuries on experimental wards were reduced after the course relative to control wards.

Attitude of Health Personnel↗

Diffusion coefficients of neurotransmitters and their metabolites in brain extracellular fluid space.

Diffusion coefficients of catecholamine neurotransmitters, their metabolites and related species was measured in brain extracellular fluid using in vivo voltammetric techniques. Nanoliter volumes of the species were pressure-ejected into the rat caudate nucleus and their concentration profiles were determined at nearby voltammetric detector electrodes. Thorough testing was carried out to show that the present methodology gave results which agreed with brain diffusion coefficients measured previously by ion-selective microelectrode techniques. All of the species which are anionic at pH 7.4 have brain diffusion coefficients about one-third of their solution counterparts in accord with earlier studies of diffusion in tortuous media. However, the brain diffusion coefficients of all the cation species are about three-times slower than those of the anions. This phenomenon is believed to be caused by ion binding with the polyanionic glycosaminoglycans and related species in brain tissue. In vitro model experiments lend support to this interpretation. This new information on biogenic amines and their metabolites provides meaningful predictions of the spatio-temporal concentration distribution of these species in the extracellular fluid.

3,4-Dihydroxyphenylacetic Acid↗

Chronoamperometry in brain slices: quantitative evaluations of in vivo electrochemistry.

Practical utilization of in vivo electrochemistry for brain studies has been impeded by difficulties with specificity and quantitative measurements. Studies in brain slices combined with similar data from intact animals have provided important new information on the nature of the electrochemical studies. Using the enzyme ascorbic acid oxidase (AAO), the primary signal contribution has been calculated to come from ascorbic acid. By inhibiting monoamine oxidase activity with pargyline, the second most important contributor in caudate extracellular fluid is postulated to be 3,4-dihydroxyphenylacetic acid. These species are calculated to constitute over 93% of the observed oxidation current in rat caudate extracellular fluid.

3,4-Dihydroxyphenylacetic Acid↗

A new type of enzyme electrode: the ascorbic acid eliminator electrode.

A new type of enzyme electrode has been developed for in vivo electrochemical measurements which allows discrimination between ascorbic acid and catecholamines and their metabolites. The electrode employs the enzyme ascorbic acid oxidase held between the voltammetric electrode and solution by a dialysis membrane or immobilized on the outer surface of serous membrane from rat small intestine. The electrode gives linear calibration curves for all catecholamines and metabolites independent of any ascorbic acid concentrations significant in physiological measurements. The electrode has been tested in brain slice measurements and shown to respond to releases of catecholamines initiated by potassium ion stimulation.

Animals↗

Suppression of pituitary and testicular function in rats by a transplanted adrenocortical carcinoma.

Snell adrenocortical carcinoma was transplanted into immature 4-week-old male rats, and the animals were sacrificed 3 weeks afterward for study of adenohypophyseal and testicular function. The weight of the tumour was 11 +/- 5 g; plasma corticosterone levels were elevated and plasma progesterone levels were massively increased compared to those in rats with no tumours. The weights of the adrenals, testes and androgen-dependent accessory reproductive glands were significantly decreased, as was the diameter of seminiferous tubules. The concentrations of testosterone, LH and FSH in the plasma were significantly reduced, whereas the levels of Prl and oestradiol were not affected. We suggest that steroid products of the transplanted tumour suppressed release of gonadotrophins from the pituitary, leading to a severe reduction of testosterone synthesis in the testes.

Adrenal Cortex Neoplasms↗