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R Tweedale

Publications and source records attributed to R Tweedale.

21 records · Page 2Linked to original sources

Hepatotoxicity of sodium valproate and other anticonvulsants in rat hepatocyte cultures.

Valproic acid has recently been shown to be associated with liver disease in man. Rat hepatocyte cultures were used to test the hepatotoxicity of valproic acid and several other anticonvulsants. Dose-related hepatotoxicity was demonstrated for valproic acid at concentrations ranging from 10 to 320 micrograms/ml, therapeutic concentrations being 50-100 micrograms/ml. Hepatotoxicity could not be demonstrated for phenobarbital, phenytoin, primidone, and clonazepam. It is concluded that valproic acid is a dose-related hepatotoxin.

Animals↗

Serum ferritin in haemochromatosis: changes in the isoferritin composition during venesection therapy.

The isoferritin composition of serum ferritin in 13 patients with untreated idiopathic haemochromatosis (IHC) has been shown to differ from normal in exhibiting an increase in isoferritins in the pH range 5.54-5.62. A similar change was observed in four patients with gross iron overload secondary to haemolytic anaemia. During the course of venesection therapy there was a progressive rise in isoferritins of pI 5.02-5.06 relative to the more basic isoferritins. These observations are consistent with previous studies showing alterations in tissue isoferritins in untreated IHC before and after venesection therapy and they are compatible with the hypothesis that the more basic isoferritins correspond to a 'storage' ferritin and the more acidic to a 'secretory' ferritin. The studies also provide further evidence for a possible biological role of the individual isoferritins.

Adult↗

Interhemispheric modulation of somatosensory receptive fields: evidence for plasticity in primary somatosensory cortex.

Extracellular recordings were made from single and multiple neurons in primary somatosensory cortex (area 3b) of macaque monkeys and flying foxes. When a small region of area 3b (or adjacent area 1) in the opposite hemisphere was cooled, thereby blocking activity that is normally transferred via the corpus callosum, larger receptive fields (RFs) were immediately unmasked for most neurons. RF expansion presumably reflects the expression of afferent inputs that are normally inhibited, suggesting that callosal inputs provide a source of tonic inhibition that contributes to the shaping of neuronal RFs. Quantitative analyses of single neuron responses revealed other effects that were consistent with a release from inhibition, such as increases in response magnitude to stimulation of points within the original RF and decreases in response latency. An unexpected finding was the reversal of these unmasking effects with extended periods of cooling: RFs returned to their original dimensions and within-field response magnitude decreased. In contrast to the initial effects, this reversal of disinhibition cannot be readily explained by an unmasking of previously unexpressed inputs. Any explanation for the reversal requires an increase in the efficacy of interneuron-mediated inhibition, and presumably occurs in response to ongoing, altered patterns of activity.

Animals↗