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Biomedical subjects

I Spence

Publications and source records attributed to I Spence.

53 records · Page 3Linked to original sources
PubMed1981

Methylaplysinopsin and other marine natural products affecting neurotransmission.

Methylaplysinopsin is a novel marine natural product that, after oral administration, prevented the effects of tetrabenazine in mice and rats. Methylaplysinopsin was a short-acting inhibitor of monoamine oxidase activity with greatest potency when serotonin was the substrate studied. The brain concentration of serotonin in the mouse was increased by methylaplysinopsin over the same time course as monoamine oxidase inhibition ex vivo. Methylaplysinopsin was also a weak inhibitor of the neuronal uptake of [3H]serotonin and a potentiator of the K+-induced release of [3H]serotonin from prelabeled synaptosomes. The predicted potentiation of serotonergic neurotransmission was supported by initial neurophysiological studies in an identified serotonergic pathway in the central nervous system of Aplysia. Two other studies on the pharmacology of marine natural products are reviewed. The majority of polyhalogenated monoterpenes isolated from red algae had central nervous system depressant properties. The exception is plocamadiene A, which caused, in mice, a reversible spastic paresis lasting up to 72 hours after oral administration. The severe muscle spasm was antagonized by diazepam. The final study discussed is the effect of a variety of marine natural products on the synthesis, neuronal uptake, and metabolism of GABA. Their selectivity is discussed with regard to the effects on metabolic respiration, and the correlation of neurochemical and neurophysiological effects on these marine substances.

Animals↗
PubMed1977

The origin of the muscle fasciculation caused by funnel-web spider venom.

The origin of the fasciculation of skeletal muscle produced by funnel-web spider venom (FSV) has been examined in mouse phrenic nerve hemi-diaphragm preparations, FSV from male spiders at concentrations greater than 10(-6) g/ ml invariably produced muscle fasciculation which could be prevented by d-tubocurarine (14micron), tetrodotoxin (0.3 micron) or by increasing the external magnesium concentration or calcium concentration. Diphenyl hydantoin (3-6 X 10(-5) M) was able to reduce these fasciculations in some experiments. In curarized preparations, multiple end plate potentials (EPPs) in response to single stimuli and bursts of spontaneous EPPs were seen in the presence of FSV (10(-5) g/ml). Extracellular recordings from phrenic nerves in the presence of FSV (10(-5) g/ml) revealed additional components in compound action potentials elicited by single stimuli, and "spontaneous" electrical activity was observed in unstimulated nerves. This spontaneous activity was abolished by raising the divalent cation concentration in the bathing solution. These results suggest that a primary site of action of FSV is the surface membrane of nerve fibres and that muscle fasciculation arises as a consequence of spontaneous action potentials produced by the venom in motor nerves.

Action Potentials↗
PubMed1974

Two types of neurones in the myenteric plexus of duodenum in the guinea-pig.

1. Intracellular recordings have been made from neurones lying in the myenteric plexus of guinea-pig duodenum; some aspects of their membrane properties have been studied by passing current through the intracellular electrode while recording changes in membrane potential.2. The current-voltage relationship was linear for small changes in membrane potential, input resistances ranging from 125 to 250 MOmega. Larger hyperpolarizing currents (causing changes of 20-40 mV) caused the input resistance to fall.3. Depolarizing currents of 1 to 10 x 10(-10) A initiated action potentials with amplitudes of up to 95 mV.4. Two types of cell were distinguished when an action potential was initiated. In one group the action potential and undershoot had a form similar to that recorded from other mammalian ganglia. In the second group an action potential was followed by both an undershoot and a prolonged afterhyperpolarization which was associated with a decrease in cell resistance.5. The two groups of cells were further distinguished by their responses to transmural stimulation. Only those cells which did not show an afterhyperpolarization could be shown to receive a synaptic input.6. The mechanism by which each cell type generates an action potential was different. The action potentials recorded from cells which had a detectable synaptic input were abolished by tetrodotoxin. In contrast, those recorded from the other type of cells persisted in the presence of tetrodotoxin. Preliminary experiments suggest that during an action potential these cells become permeable to both sodium and calcium ions.7. Abolition of the calcium component of the action potential in cells which generated an afterhyperpolarization abolished this latter potential.8. The role of these two groups of cells is discussed.

Journal Article↗
PubMed1970

An assessment of the Coulter counter model S.

An assessment of the Coulter model S automatic blood counter has been carried out. The standard deviations for the haemoglobin concentration, haematocrit, red cell count, and white cell count are, respectively, +/- 0.15 g/100 ml, +/- 0.45%, +/- 0.04 m/c mm, and +/- 0.47 thous/c mm. These results are clearly more accurate than careful manual estimates, performed for comparison on the same samples. Details of the comparisons are presented. A comparison is also made with routine daily estimations.;Carryover' from one sample to the next was found to be about 2%, and tests in the ranges likely to be found in practice showed good linearity for the haemoglobin estimation, haematocrit, red cell count, and white cell count. A brief account of instrument failures is given.The performance of the Coulter model S compares well with that of other automated equipment for which detailed evaluations are available.

Blood Cell Count↗
PubMedDate not supplied

Using artificial neural networks to classify the activity of capsaicin and its analogues.

Back-propagation artificial neural networks (ANNs) were trained with parameters derived from different molecular structure representation methods, including topological indices, molecular connectivity, and novel physicochemical descriptors to model the structure--activity relationship of a large series of capsaicin analogues. The ANN QSAR model produced a high level of correlation between the experimental and predicted data. After optimization, using cross-validation and selective pruning techniques, the ANNs predicted the EC50 values of 101 capsaicin analogues, correctly classifying 34 of 41 inactive compounds and 58 of 60 active compounds. These results demonstrate the capability of ANNs for predicting the biological activity of drugs, when trained on an optimal set of input parameters derived from a combination of different molecular structure representations.

Capsaicin↗
PubMedDate not supplied

Retrocaval ureter.

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Adult↗