Investigation of the effects of the novel anticonvulsant compound carisbamate(RWJ-333369) on rat piriform cortical neurones in vitro

Background and purpose: Carisbamate is being developed for adjuvant treatment of partial onset epilepsy. Carisbamate produces anticonvulsant effects in primary generalized, complex partial and absence-type seizure models, and exhibits neuroprotective and antiepileptogenic properties in rodent epilepsy models. Phase IIb clinical trials of carisbamate demonstrated efficacy against partial onset seizures; however, its mechanisms of action remain unknown. Here, we report the effects of carisbamate on membrane properties, evoked and spontaneous synaptic transmission and induced epileptiform discharges in layer II-III neurones in piriform cortical brain slices. Experimental approach: Effects of carisbamate were investigated in rat piriform cortical neurones by using intracellular electrophysiological recordings. Key results: Carisbamate (50–400 mmol·L-1) reversibly decreased amplitude, duration and rise-time of evoked action potentials and inhibited repetitive firing, consistent with use-dependent Na+ channel block; 150–400 mmol·L-1 carisbamate reduced neuronal input resistance, without altering membrane potential. After microelectrode intracellular Cl- loading, carisbamate depolarized cells, an effect reversed by picrotoxin. Carisbamate (100–400 mmol·L-1) also selectively depressed lateral olfactory tract-afferent evoked excitatory synaptic transmission (opposed by picrotoxin), consistent with activation of a presynaptic Cl conductance. Lidocaine (40–320 mmol·L-1) mimicked carisbamate, implying similar modes of action. Carisbamate (300–600 mmol·L-1) had no effect on spontaneous GABAA miniature inhibitory postsynaptic currents and at lower concentrations (50–200 mmol·L-1) inhibited Mg2+-free or 4-aminopyridine-induced seizure-like discharges. Conclusions and implications: Carisbamate blocked evoked action potentials use-dependently, consistent with a primary action on Na+ channels and increased Cl- conductances presynaptically and, under certain conditions, postsynaptically to selectively depress excitatory neurotransmission in piriform cortical layer Ia-afferent terminals.

A preliminary investigation of the release of oil from contaminated clays and other fine-grained sediments during consolidation

Fine-grained sediments on land, or in a freshwater or marine environment, may become contaminated with a wide range of pollutants including hydrocarbons. This paper is concerned with preliminary studies of the mobilization and transportation of hydrocarbons, during the process of consolidation, to adjacent sediments or water bodies. A modified Rowe Cell was used to measure the consolidation properties of prepared kaolinite and bentonite clay-water slurries, with and without the addition of oil, along with hydrocarbon-bearing drill-cuttings samples taken from the sea-bed adjacent to two North Sea oil-well platforms. The consolidation properties of the kaolinite and bentonite clay slurries were little altered by the addition of oil, which was present at concentrations of between 8073 and 59 572 mg kg(-1). During each consolidation stage, samples of the expelled pore-fluids were collected and analysed for oil content. These values were very low in comparison with the original oil concentration in the samples and changed little between each consolidation stage. Analysis of the slurry samples both before and after consolidation confirms that, proportionally, little oil is removed as a result of consolidation. The implication of these results is that, for the range of samples tested, the very high hydraulic gradients and particle rearrangements that occur during the process of consolidation are capable of releasing only proportionally small amounts of oil bound to the fine-grained clay and silt particles.

A preliminary investigation into mining and smelting impacts on trace element concentrations in the soils and vegetation around Tharsis, SW Spain

Toxic trace elements present an environmental hazard in the vicinity of mining and smelting activities. However. the processes of transfer of these elements to groundwater and to plants are not always clear. Tharsis mine. in the Iberian pyrite belt (SW Spain), has been exploited since 2500 BC, with extensive smelting, taking place front the 1850S until the 1920s. Sixty four soil (mainly topsoils) and vegetation samples were collected in February 2001 and analysed by ICP-AES for 23 elements. Concentrations are 6-6300 mg kg(-1) As and 14-24800 mg kg(-1) Pb in soils, and 0.20-9 mg kg(-1) As and 2-195 mg Pb in vegetation. Trace element concentrations decrease rapidly away from the mine. with As and Pb concentrations in the range 6-1850 mg kg(-1) (median 22 mg kg(-1)) and 14-31 mg, kg(-1) (median 43 mg, kg(-1)), respectively, 1 km away from the mine. These concentrations are low when compared to other well-studied mining and smelting areas (e.g. 600 mg kg(-1) As at 8 km from Yellowknife smelter, Canada; >100 mg kg(-1) Pb over 270 km(2) around the Pb-Zn Port Pirie smelter. South Australia: mean of 1419 mg kg(-1) Pb around Aberystwyth smelter, Wales, UK). The high metal content of the vegetation and the low soil pH (mean pH 4.93) indicate the potential for trace element mobility which Could explain the relatively low concentration of metals in Tharsis topsoils and cause threats to plans to redevelop the Tharsis area as an orange plantation.