Effects of external calcium on horizontal cells in the superfused goldfish retina.
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Biomedical subjects
Publications and source records attributed to J S Rowe.
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Membrane potentials of retinal horizontal cells have been recorded fro isolated fish retinae perfused with Ringer solutions containing various drugs. We show that glutamate diethyl ester (GDEE) and gamma-D-glutamylglycine (DGG), respectively antagonists of the excitatory neurotransmitter agonists quisqualate and kainate, hyperpolarize horizontal cells and, at mM concentrations, suppress the light evoked S-potentials. They were not, however, generally effective in blocking the depolarizing effects of exogenous kainate and quisqualate, but in the 10% of the experiments where they were effective GDEE blocked selectively quisqualate binding the DGG blocked selectively kainate binding. In contrast, folic acid consistently hyperpolarized the horizontal cells and at mM concentrations, blocked partially the effects of kainate and quisqualate. These results are consistent with the depolarizing actions of kainate and quisqualate on retinal horizontal cells [9, 10], but the inconsistent blocking of kainate and quisqualate effects by DGG and GDEE seriously restricts their value as a tool in retinal neurophysiology.
We have recorded the intracellular membrane potential of horizontal cells, second-order interneurones of the vertebrate retina, from fish retinae perfused with Ringer solution containing agonist drugs of the excitatory neurotransmitters, L-glutamate and L-aspartate. We show that at concentrations greater than about 10 microM, kainate and quisqualate have a potent depolarizing effect on horizontal cells and suppress their light evoked electrical responses (S-potentials). In contrast, a third agonist, N-methyl-D-aspartate, hyperpolarizes horizontal cells. The depolarizing action of kainate and quisqualate persists in the presence of the synaptic blocker, cobalt chloride, which implies that they bind directly on the horizontal cell membranes. Two kainate-related drugs, which are active on invertebrate neurones, were also examined, one, alpha-ketokainate, simulates the action of kainate, but the other, dihydrokainate, is ineffective on horizontal cells. L-Glutamate binds with high affinity at quisqualate sites, whereas L-aspartate binds with high affinity at NMDA sites, thus we conclude that L-glutamate is the likely neurotransmitter at the photoreceptor-horizontal cell synapse.
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The influence of dose on the in vitro metabolism of indomethacin has been investigated in four laboratory species (rat, rabbit, guinea pig, hamster). It was found that in the rat and guinea pig the ratio of deacylated to demethylated metabolites was dependent on the substrate concentration of indomethacin, whereas in the rabbit the ratio remained constant in the dosage range investigated (1-10 mumoles). No demethylated product was found in the hamster but a high level of activity of the deacylase enzyme was observed. These findings may help to explain species-dependent toxicity.
We studied the effect of th bite acid sequestrant colestipol, alone and in combination with clofibrate or niacin, in patients with heterozygous familial hypercholesterolemia who were given a diet low in cholesterol and saturated fat. With colestipol alone, mean cholesterol levels in serum decreased 16 to 25 per cent. The addition of clofibrate produced a total mean decrement of only 28 per cent. In contrast, serum cholesterol levels fell 45 per cent when colestipol as combined with niacin. Low-density-lipoprotein (LDL) cholesterol decreased 55 per cent with colestipol and niacin, whereas high-density-lipoprotein (HDL) cholesterol increased. Mean LDL cholesterol was lower in patients given this regimen than in matched normal controls eating an unrestricted diet. Tendinous xanthomas, measured by quantitative xeroradiography, were significantly reduced (P < 0.01), indicating that this regimen mobilized cholesterol from tissue pools with slow turnover. Colestipol plus niacin promises to be useful in the treatment of patients at high risk from elevated levels of LDL.
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The effects of the core toi colloid wall ratio and particle size of the core on the in vitro release of indomethacin microcapsules prepared by the gelatin-acacia complex coacervation process have been examined. All formulations showed a zero order release pattern after an initial burst phase. The release rate increased with increasing core to coat ratios and decreasing particle size of core material. In vivo plasma level studies showed no difference in bioavailability between different microcapsule formulations or a conventional indomethacin capsule. In vitro release studies on a commercially available sustained release formulation of indomethacin (Indocid R) were slower than any of the microcapsule formulations and exhibited a square root t dependence indicating a diffusion controlled process from a matrix formulation. In vivo studies show this formulation to have a longer smoother plasma concentration than the microcapsule formulation, and to avoid high initial peak values of drug. Thus from the in vitro studies a sustained release effect was not unexpected but the in vitro differences between the microcapsule products were not paralleled by the in vivo behaviour. These results illustrate some of the problems in extrapolation of in vitro dissolution data to the in vivo situation.
Examination of the distribution of vagus nerve fibers to the stomach in 100 cadavers revealed considerable individual variation. No single pattern shown in textbooks or published papers can be accepted as correct for all individuals. The variations encountered are discussed from the viewpoint of the surgeon who wishes to perform highly selective vagotomy.
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The topographic anatomy of the submandibular triangle and its contents are described in terms of four surgical planes, with considerations of the anatomic complications during surgery. Attention is called to the importance of identifying and sparing five nerves in this triangle--the mandibular and cervical branches of the facial nerve, the hypoglossal nerve, the lingual nerve, and the chorda tympani.
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