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.

A preliminary investigation into the use of ochre as a remedial amendment in arsenic-contaminated soils

Ochre is an unwanted waste product that accumulates in wetlands and streams draining abandoned coal and metal mines. A potential commercial use for ochre is to remediate As contaminated soil. Arsenic contaminated soil (605 mg kg(-1)) was mixed with different ochres (A, B and C) in a mass ratio of 1:1 and shaken in 20 mL of deionised water. After 72 h As concentration in solution was ca. 500 mu g kg(-1) in the control and 1-2.5 mu g kg(-1) in the ochre treated experiments. In a second experiment soil:ochre mixtures of 0.05-1:1 were shaken in 20 mL of deionised water for 24 h. For Ochres A and C, as Solution concentration was reduced to ca. 1 mu gkg(-1) by 0.2-1:1 ochre:soil mixtures. For Ochre B, as concentration only reached ca. 1 mu g kg(-1) in the 1:1 ochre:soil inix. Sorption of As was best modelled by a Freundlich isotherm using As sorption per mass of goethite in the ochre (log K= 1.64, n = 0.79, R-2 = 0.76, p <= 0.001). Efficiency of ochre in removing As from solution increased with increasing total Fe, goethite, citrate dithionite extractable Fe and surface area. (c) 2005 Elsevier Ltd. All rights reserved.

Salt marsh morphodynamics: An investigation of tidal flows and marsh channel equilibrium

Although numerous field studies have evaluated flow and transport processes in salt marsh channels, the overall role of channels in delivering and removing material from salt marsh platforms is still poorly characterised. In this paper, we consider this issue based on a numerical hydrodynamic model for a prototype marsh system and on a field survey of the cross-sectional geometry of a marsh channel network. Results of the numerical simulations indicate that the channel transfers approximately three times the volume of water that would be estimated from mass balance considerations alone. Marsh platform roughness exerts a significant influence on the partitioning of discharge between the channel and the marsh platform edge, alters flow patterns on the marsh platform due to its effects on channel-to-platform transfer and also controls the timing of peak discharge relative to marsh-edge overtopping. Although peak channel discharges and velocities are associated with the flood tide and marsh inundation, a larger volume of water is transferred by the channel during ebb flows, a portion of which transfer takes place after the tidal height is below the marsh platform. Detailed surveys of the marsh channels crossing a series of transects at Upper Stiffkey Marsh, north Norfolk, England, show that the total channel cross-sectional area increases linearly with catchment area in the inner part of the marsh, which is consistent with the increase in shoreward tidal prism removed by the channels. Toward the marsh edge, however, a deficit in the total cross-sectional area develops, suggesting that discharge partitioning between the marsh channels and the marsh platform edge may also be expressed in the morphology of marsh channel systems.

Dr John Snow and an early investigation of groundwater contamination

John Snow was a physician but his studies of the way in which cholera is spread have long attracted the interest of hydrogeologists. From his investigation into the epidemiology of the cholera outbreak around the well in Broad Street, London, in 1854, Snow gained valuable evidence that cholera is spread by contamination of drinking water. Subsequent research by others showed that the well was contaminated by sewage. The study therefore represents one of the first, if not the first, study of an incident of groundwater contamination in Britain. Although he had no formal geological training, it is clear that Snow had a much better understanding of groundwater than many modern medical practitioners. At the time of the outbreak Snow was continuing his practice as a physician and anaesthetist. His casebooks for 1854 do not even mention cholera. Yet, nearly 150 years later, he is as well known for his work on cholera as for his pioneering work on anaesthesia, and his discoveries are still the subject of controversy.

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.