Benzimidazolones enhance the function of epithelial Na⁺ transport.

BACKGROUND AND PURPOSE: Pharmacological enhancement of vectorial Na⁺ transport may be useful to increase alveolar fluid clearance. Herein, we investigated the influence of the benzimidazolones 1-ethyl-1,3-dihydro-2-benzimidazolone (1-EBIO), 5,6-dichloro-1-EBIO (DC-EBIO) and chlorzoxazone on vectorial epithelial Na⁺ transport. EXPERIMENTAL APPROACH: Effects on vectorial Na⁺ transport and amiloride-sensitive apical membrane Na⁺ permeability were determined by measuring short-circuit currents (I(SC)) in rat fetal distal lung epithelial (FDLE) monolayers. Furthermore, amiloride-sensitive membrane conductance and the open probability of epithelial Na⁺ channels (ENaC) were determined by patch clamp experiments using A549 cells. KEY RESULTS: I(SC) was increased by approximately 50% after addition of 1-EBIO, DC-EBIO and chlorzoxazone. With permeabilized basolateral membranes in the presence of a 145:5 apical to basolateral Na⁺ gradient, the benzimidazolones markedly increased amiloride-sensitive I(SC). 5-(N-Ethyl-N-isopropyl)amiloride-induced inhibition of I(SC) was not affected. The benzamil-sensitive I(SC) was increased in benzimidazolone-stimulated monolayers. Pretreating the apical membrane with amiloride, which inhibits ENaC, completely prevented the stimulating effects of benzimidazolones on I(SC). Furthermore, 1-EBIO (1 mM) and DC-EBIO (0.1 mM) significantly increased (threefold) the open probability of ENaC without influencing current amplitude. Whole cell measurements showed that DC-EBIO (0.1 mM) induced an amiloride-sensitive increase in membrane conductance. CONCLUSION AND IMPLICATIONS: Benzimidazolones have a stimulating effect on vectorial Na⁺ transport. The antagonist sensitivity of this effect suggests the benzimidazolones elicit this action by activating the highly selective ENaC currents. Thus, the results demonstrate a possible new strategy for directly enhancing epithelial Na⁺ transport.

Seasonal variation of Titan's atmospheric structure simulated by a general circulation model.

The seasonal variation of Titan's atmospheric structure with emphasis on the stratosphere is simulated by a three-dimensional general circulation model. The model includes the transport of haze particles by the circulation. The likely pattern of meridional circulation is reconstructed by a comparison of simulated and observed haze and temperature distribution. The GCM produces a weak zonal circulation with a small latitudinal temperature gradient, in conflict with observation. The direct reason is found to be the excessive meridional circulation. Under uniformly distributed opacity sources, the model predicts a pair of symmetric Hadley cells near the equinox and a single global cell with the rising branch in the summer hemisphere below about z = 230 km and a thermally indirect cell above the direct cell near the solstice. The interhemispheric circulation transports haze particles from the summer to the winter hemisphere, causing a maximum haze opacity contrast near the solstice and a smaller contrast near the equinox, contrary to observation. On the other, if the GCM is run under modified cooling rate in order to account for the enhancement in nitrites and some hydrocarbons in the northern hemisphere near the vernal equinox, the meridional cell at the equinox becomes a single cell with rising motions in the autumn hemisphere. A more realistic haze opacity distribution can be reproduced at the equinox. However, a pure transport effect (without particle growth by microphysics, etc.) would not be able to cause the observed discontinuity of the global haze opacity distribution at any location. The stratospheric temperature asymmetry can be explained by a combination of asymmetric radiative heating rates and adiabatic heating due to vertical motion within the thermally indirect cell. A seasonal variation of haze particle number density is unlikely to be responsible for this asymmetry. It is likely that a thermally indirect cell covers the upper portion of the main haze layer. An artificial damping of the meridional circulation enables the formation of high-latitude jets in the upper stratosphere and weaker equatorial superrotation. The latitudinal temperature distribution in the stratosphere is better reproduced.

[Prevalence of medullary sponge kidney in patients with and without nephrolithiasis]. / Prävalenz der Markschwammniere bei Patienten mit und ohne Nierensteinleiden.

Reports on the prevalence of medullary sponge kidneys have given conflicting results. The present work is aimed at defining the prevalence of this abnormality in renal stone formers compared with a non-stone-forming control population by strict radiological criteria. Three separate studies have been carried out: the retrospective analysis of 191 intravenous urographies, which had been performed in 1988; the respective prospective analysis of 104 consecutive intravenous urographies and of 149 consecutive urographies, which had been performed at the end of intravenous digitalized subtraction renal angiographies. The 444 patients were classified according to presence or absence of nephrolithiasis. After exclusion of 70 patients (16%) of which the X-ray didn't fulfill the quality criteria, urographies were classified as 'medullary sponge kidneys', 'papillary blush' or 'negative' according to the radiological aspect of the papillae. Diagnosis of medullary sponge kidneys was based on presence of at least three linear or round papillary opacities seen in at least on papilla even of one kidney on late films (at least ten minutes after injection of contrast medium), taken without ureteral obstruction or abdominal compression. Overall results reveal that prevalence of a medullary sponge kidney in renal stone formers (8.5%) is significantly (p < 0.01) higher than in the control population (1.5%) and higher than what has been generally reported. Results of the retrospective and of both prospective analysis did not significantly differ. The best diagnostic tool to unmask medullary sponge kidneys remains urography.

Temperature-induced changes in the composition of floatglass surfaces.

Floatglass is an important kind of commercial glass, comprising the main body of modern flat glass used in buildings and vehicles. The stoichiometry of the surface layer differs from that of the bulk and will usually change due to subsequent high-temperature process steps or attack by water or humidity. Glass samples have been investigated by means of ion beam analysis. Using resonant nuclear reaction analysis ((15)N technique), hydrogen concentration profiles have been determined. Profiles of the heavier glass constituents, especially sodium and tin, have been obtained by RBS. Changes in the composition of the floatglass surfaces caused by subsequent temperature treatment (up to 700 ( degrees )C) and by controlled hydration treatment are reported. Possible mechanisms of hydrogen uptake and release are discussed.