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Biomedical subjects

R N Adams

Publications and source records attributed to R N Adams.

At least 55 records · Page 3Linked to original sources
PubMed1985

Effect of CO2 on a brain extracellular space marker and evidence of its neuronal modulation.

Increases in inspired CO2 consistently altered the local concentration of the brain extracellular space marker alpha-naphthalene sulfonate (alpha-NS) as measured with ion-selective micropipettes in the rat thalamus. Stereotaxic injection of lidocaine in the region of the locus coeruleus attenuated this effect of CO2, and amitriptyline, a tricyclic anti-depressant and amine reuptake inhibitor, potentiated the effect. These results suggest that metabolic demand, as mimicked here by the addition of CO2, alters the fluid environment of the brain and central noradrenergic mechanisms may modulate this response.

Amitriptyline↗
PubMed1985

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↗
PubMed1985

Simultaneous monitoring of voltammetric and ion-selective electrodes in mammalian brain.

A new technique of simultaneously recording from ion-selective and voltammetric microelectrodes in vivo allows one to measure concomitant ionic and monoamine neurotransmitter fluxes in the extracellular fluid space of the brain. Examples are presented of the results obtained with various drug and stimulus applications. The time correlations of the ionic and neurotransmitter fluxes are especially useful in attempting to better understand the possible interactions of these chemical dynamics with neuronal functioning.

Animals↗
PubMed1985

Treatment of experimental myasthenia gravis with cyclosporin A.

Cyclosporin A (CsA) is an immunosuppressive agent that has recently been used to prevent rejection of transplanted tissues. The effects of CsA treatment of rats with experimental autoimmune myasthenia gravis (EAMG), an antibody-mediated autoimmune disorder of acetylcholine receptors (AChRs) at neuromuscular junctions, have been studied. CsA treatment at the time of primary immunization suppressed the antibody responses to AChR virtually completely. Following 12 weeks of CsA, the AChR-immunized rats responded like naive controls to a further challenge of AChR. Treatment of ongoing EAMG resulted in a reduction of AChR antibody by more than 50%. The secondary response to a challenge of AChR was prevented by CsA treatment, but a very large challenge dose in adjuvant partially overwhelmed the effect of CsA. CsA treatment also prevented the loss of AChRs at neuromuscular junctions, as compared with untreated EAMG controls (P less than 0.02). The efficacy of CsA in suppressing ongoing and secondary hetero- and autoimmune responses against AChR in EAMG encourages its ultimate application in autoimmune diseases of man, such as MG. Its usefulness will depend on the ability to determine effective doses of CsA that are well tolerated.

Animals↗
PubMed1985

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↗
PubMed1984

Adrenergic transmission in hippocampus-locus coeruleus double grafts in oculo: demonstration by in vivo electrochemical detection.

In vivo electrochemical detection was used to study transmitter release from a synaptically or pharmacologically stimulated noradrenergic isolated pathway formed by double in oculo brain tissue grafts. Retinal illumination, which activates cholinergic nerve fibers that grow into intraocular grafts from the autonomic ground plexus of the iris, produced increases in the concentration of electroactive species in the hippocampal portion of intraocular locus coeruleus-hippocampus double grafts. This response was potentiated after cholinesterase inhibition, and mimicked by perfusion of carbachol, a muscarinic agonist. Much smaller increases in the electroactive species were measured in reserpinized animals, and this minimal response was completely eliminated by the subsequent inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine. Taken together, the data suggest that synaptically released transmitter in these isolated brain circuits can be measured using in vivo electrochemical detection techniques, and lend further support to the hypothesis that in oculo locus coeruleus grafts develop a functional catecholaminergic input to sequentially grafted hippocampus.

Animals↗
PubMed1984

Nafion-coated electrodes with high selectivity for CNS electrochemistry.

A major improvement in the selectivity of small graphite electrodes used for in vivo electrochemistry is described. The electrodes are coated with Nafion, a perfluorosulfonated polymer. This coating is practically impermeable to ascorbic acid and anionic biogenic amine metabolites and only slightly responsive to neutral metabolites. Thus it becomes selective for the cationic primary neurotransmitters, dopamine, norepinephrine and 5-hydroxytryptamine. Responses of Nafion-coated and untreated electrodes in vivo are compared.

Animals↗
PubMed1983

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↗
PubMed1983

Catecholamine distribution patterns in rat thalamus.

Detailed distribution patterns for norepinephrine and dopamine in rat thalamus were determined by liquid chromatographic assays. The norepinephrine distribution is in good accord with that suggested previously by neuroanatomical tracing techniques. Detailed anterior-posterior concentration profiles for norepinephrine are summarized. An unexpected finding was a strong animal variability in thalamic dopamine content. Thalami were distinguished as having either low, intermediate or extremely high dopamine concentrations.

Animals↗
PubMed1983

Combined short-term immunotherapy for experimental autoimmune myasthenia gravis.

A therapeutic strategy was designed to eliminate the humoral immune response to acetylcholine receptor (AChR) in ongoing experimental autoimmune myasthenia gravis (EAMG). Rats with EAMG were treated with a protocol consisting of three components: (1) A single high dose of cyclophosphamide (200 mg/kg) was used to produce a rapid and sustained fall in the anti-AChR antibody levels by preferential destruction of antibody-producing B-lymphocytes. "Memory" lymphocytes were not eliminated by cyclophosphamide. (2) Irradiation (600 rads) was used to eliminate the "memory" cells. It eliminated the anamnestic response to a challenge with the antigen AChR. (3) Bone marrow transplantation was used to repopulate the hematopoietic system after the otherwise lethal dose of cyclophosphamide. We used bone marrow from syngeneic rats with active EAMG to simulate an autologous transplant. Rats with EAMG treated with this combined protocol showed a prompt and sustained fall in the anti-AChR antibody levels and had no anamnestic response to a challenge with AChR. Thus, an affected animal's own marrow could be stored and used later for repopulation after cyclophosphamide-irradiation treatment. This treatment eliminates the animal's ongoing immune responses and reconstitutes the immune system in its original state. The success of this approach suggests that, if their safety could be established, similar "curative" strategies might be developed for the treatment of patients with severe antibody-mediated autoimmune disorders, such as myasthenia gravis.

Animals↗
PubMed1982

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↗
PubMed1982

Functional activities of autoantibodies to acetylcholine receptors and the clinical severity of myasthenia gravis.

The pathogenesis of myasthenia gravis involves a humorally mediated autoimmune attack directed against acetylcholine receptors of skeletal muscles. Antibodies against acetylcholine receptors are detected in the serum of more than 80 per cent of patients, but the antibody titers correspond poorly with the severity of disease. To distinguish between antibody titers and antibody activity, we measured the ability of serum immunoglobulin from 49 patients to induce accelerated degradation or blockade of the binding sites of acetylcholine receptors, using a mammalian skeletal-muscle tissue-culture system. Immunoglobulin from 41 of 45 patients tested (91 per cent) increased the rate of degradation of acetylcholine receptors, and the relative increase in the degradation rate corresponded closely (P less than 0.001) with clinical status. Immunoglobulin from 42 of 48 patients tested (88 per cent) produced blockade of receptors, and the extent of the blockade also corresponded with clinical status (P less than 0.001). An index of the combined activities of the immunoglobulin in accelerating degradation and producing blockade of acetylcholine receptors was elevated in 43 of 44 patients (98 per cent) whose immunoglobulins were tested for both activities; this index predicted the patients' clinical status significantly better (P less than 0.001) than either measure alone. This finding suggests that the functional ability of antibodies to decrease the number of available acetylcholine receptors by these two mechanisms is clinically relevant in the pathogenesis of myasthenia gravis.

Autoantibodies↗