RESUMEN
A heated multicapillary inlet and ion funnel interface was developed to couple an electrospray ionization (ESI) source to a high-vacuum stage for obtaining improved sensitivity in mass spectrometric applications. The inlet was constructed from an array of seven thin-wall stainless steel tubes soldered into a central hole of a cylindrical heating block. An electrodynamic ion funnel was used in the interface region to more effectively capture, focus, and transmit ions from the multicapillary inlet. The interface of seven capillary inlets with the ion funnel showed more than 7 times higher transmission efficiency compared to that of a single capillary inlet with the ion funnel and a 23-fold greater transmission efficiency than could be obtained using the standard orifice-skimmer interface of a triple-quadrupole MS. The multiple-capillary inlet and ion funnel interface showed an overall 10% ion transmission efficiency and approximately 3-4% overall detection efficiency of ions from solution based (i.e., prior to electrospray). The improved performance was achieved under conditions where ESI operation is robust and results in a significant increase in dynamic range.
RESUMEN
These studies were conducted in order to establish the dose dependency and relative peripheral versus central activity of four prototypical cholinergic antagonists on the rodent passive avoidance response, a widely used animal model of retention. Subcutaneous administration of 0.1 to 100mg/kg revealed a potency profile of scopolamine > atropine methylscopolamine >/= methylatropine for the impairment of passive avoidance responding. A series of neurological assessments of the doses used indicated that side effects alone were not sufficient to impair passive avoidance responding. Although inactive when delivered peripherally, methylatropine was able to produce retention deficits at 10nmol (3.66µg) when administered intracerebrally. To further evaluate whether systemic methylatropine could enter the central nervous system, either scopolamine or atropine was administered subcutaneously in mice and rats pretreated with 10-100mg/kg methylatropine. The deficit-producing effects of scopolamine and atropine were abolished with methylatropine. Thus methylatropine is an exclusive peripheral antagonist; its ability to block the deficit-producing effects of scopolamine and atropine may occur through a change in blood-brain barrier permeability or through uncharacterized pharmacokinetic properties.
RESUMEN
Felbamate is a novel anticonvulsant agent recently approved by the FDA for treatment of epilepsy in the US. While the mechanism of action of felbamate has not been fully eludicated, recent evidence has accumulated to suggest that felbamate may act at the strychnine-insensitive glycine binding site on the NMDA receptor complex. Since this receptor has been strongly implicated in cognitive processes, the current study was designed to investigate the potential effects of felbamate on learning performance. Doses of felbamate up to 1000mg/kg, administered subcutaneously (s.c.), did not produce deleterious effects on performance in either mice or rats, using a passive avoidance task. In contrast, the non-competitive NMDA antagonist dizocilpine produced performance deficits at doses from 0.1 to 1.0mg/kg s.c. in both rats and mice. Felbamate and dizocilpine prevented NMDA-induced convulsions with ED(50)s of 20.3 and 0.82mg/kg s.c., respectively. Calculations for the therapeutic index (ratio of the deficit-producing to anticonvulsant doses) for dizocilpine resulted in less than a 1-fold separation in dose, while the therapeutic index for felbamate was greater than 50. Taken together, these results indicate that felbamate does not produce cognitive deficits at doses more than 50 times the dose needed to block seizure activity in animals.
RESUMEN
Transmission electron microscope samples of two types of metal matrix composites were prepared using both traditional thinning methods and the more novel focused ion beam miller. Electropolishing methods were able to produce, very rapidly, thin foils where the matrix was electron transparent, but the ceramic reinforcement particles remained unthinned. Thus, it was not possible in these foils to study either the matrix-reinforcement interface or the microstructure of the reinforcement particles themselves. In contrast, both phases in the composites prepared using the focused ion beam miller thinned uniformly. The interfaces in these materials were clearly visible and the ceramic reinforcement was electron transparent. However, microstructural artifacts associated with ion beam damage were also observed. The extent of these artifacts and methods of minimizing their effect were dependent on both the materials and the milling conditions used.