Lamotrigine (LTG), 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine, is a structurally novel anticonvulsant. The anticonvulsant profile of LTG following oral administration in two standard anticonvulsant tests, the maximal electroshock (MES) test in mice and rats and the pentylenetetrazol (PTZ) infusion test in mice, was studied in comparison with the known anticonvulsant drugs phenytoin (PHT), phenobarbitone, diazepam, carbamazepine (CBZ), sodium valproate, ethosuximide (ETH), and troxidone (TROX). ED50 values for the abolition of hindlimb extension (HLE) in the MES test and PTZ infusion tests and doses increasing the latency of PTZ-evoked clonus were determined. The duration of action of LTG was examined in rats and mice in the MES test by determining ED50 values for the abolition of HLE at various drug intervals to shock administration. In the MES test, LTG was well absorbed in both species, with peak activity at 1 h and persistence at this level of potency for at least 8 h. Of the drugs examined, LTG was ranked the most potent and persistent in both species. LTG also abolished PTZ-evoked HLE, while ETH and TROX were inactive. Clonus latency was not increased by LTG, PHT, or CBZ, but was significantly increased (p less than 0.05) by the remaining anticonvulsants. Thus, LTG resembled PHT and CBZ in its ability to block HLE but not to increase PTZ-induced clonus latency. Acute behavioural studies in mice and rats have suggested a wide separation between anticonvulsant doses and those producing behavioural impairment. These results suggest that LTG may be of value in the treatment of generalised tonic-clonic and partial seizures.
The Silent Canyon volcanic center consists of a buried Miocene peralkaline caldera complex and outlying peralkaline lava domes. Its location has been corroborated by geophysical data and more than 50 drill holes. Two widespread ash flow sheets, the Tub Spring and overlying Grouse Canyon members of the Miocene Belted Range Tuff, were erupted from the caldera complex and have volumes of 60–100 km3 and 200 km3, respectively. Eruption of the ash flows was preceded by widespread extrusion of precaldera comendite domes and was followed by extrusion of postcollapse peralkaline lavas and tuffs within and outside the caldera complex. Lava flows and tuffs were also deposited between the two major ash flow sheets. Rocks of the Silent Canyon center vary significantly in silica content and peralkalinity. The most mafic rocks are precollapse and postcollapse trachytes (65–69% SiO2). Low‐silica comendites (69–73% SiO2) were erupted as the mafic upper part of the chemically zoned Grouse Canyon Member and as postcollapse lavas. The lower part of the Grouse Canyon Member and the underlying rhyolite of Split Ridge are moderately peralkaline comendite (PI is molar ratio Na + K/Al is 1.17–1.26). These comendites have major element characteristics and trace element enrichments approaching those of pantellerites. The Tub Spring Member, by contrast, is a weakly peralkaline chemically unzoned silicic comendite (75–76% SiO2) ash flow tuff. Weakly peralkaline silicic comendites (PI 1.0–1.1) are the most abundant precaldera lavas. Postcollapse lavas range from trachyte to silicic comendite; some have anomalous light rare earth element (LREE) enrichments. Silent Canyon rocks follow a common petrologic evolution from trachyte to low‐silica comendite; above 73% SiO2, compositions of the moderately peralkaline comendites diverge from those of the weakly peralkaline silicic comendites. These contrasting differentiation paths are shown in the behavior of Fe and other transition metals, Al, Na, K; the trace elements Ba, Zr, Nb; and probably F and Cl. Weakly peralkaline silicic comendites show a LREE/heavy REE crossover in early erupted/late erupted rocks; moderately peralkaline comendites are enriched in all REE. The development of divergent peralkaline magmas, toward both pantelleritic and weakly peralkaline compositions, is unusual in a single volcanic center.
About 40% of human erythrocyte membrane protein is resistant to solubilization in 0.5% Triton X-114. These components comprise a structure called a Triton shell roughly similar in size and shape to the original erythrocyte and thus constitute a cytoskeleton. With increasing concentrations of Triton the lipid content of the Triton shell decreases dramatically, whereas the majority of the protein components remain constant. Exceptions to this rule include proteins contained in band 3, the presumed anion channel, and in band 4 which decrease with increasing Triton concentration. The Triton-insoluble complex includes spectrin (bands 1 and 2), actin (band 5), and bands 3' and 7. Component 3' has an apparent molecular weight of 88,000 daltons as does 3; but unlike 3, it is insensitive to protease treatment of the intact cell, has a low extinction coefficient at 280 nm, and is solubilized from the shells in alkaline water solutions. Component 7 also has a low extinction coefficient at 280 nm. Spectrin alone is solubilized from the Triton shells in isotonic media. The solubilized spectrin contains no bound Triton and coelectrophoreses with spectrin eluted in hypotonic solutions from ghosts. Electron micrographs of fixed Triton shells stained with uranyl acetate show the presence of numerous filaments which appear beaded and are 80--120 A in diameter. The filaments cannot be composed mainly af actin, but enough spectrin is present to form the filaments. Triton shells may provide an excellent source of material useful in the investigation of the erythrocyte cytoskeleton.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.