ZD4054 is an oral specific endothelin-A receptor antagonist in development for the treatment of hormone-resistant prostate cancer. Both renal and metabolic processes contribute to its overall clearance. Two preclinical in vitro studies investigated the metabolism of ZD4054 using human liver microsomes, individual cytochrome P450 (CYP) isozymes, and flavin-containing monooxygenase isoforms. Two Phase I open-label crossover volunteer studies subsequently investigated in vivo drug interactions between ZD4054 and the CYP450 inducer rifampicin or CYP3A4 inhibitor itraconazole. The most abundant metabolite produced in in vitro incubations accounted for 12.8% of radioactivity after ZD4054 was incubated with CYP3A4. No significant flavin-containing monooxygenase metabolism of ZD4054 was observed. In the in vivo studies, rifampicin co-administration reduced the area under the concentration–time curve and maximum plasma concentration of ZD4054 by 68% and 29%, respectively, whilst co-administration with itraconazole was associated with an increase in ZD4054 area under the curve of approximately 28%. While co-administration of CYP450 inducers might be associated with reduced efficacy of ZD4054, dose reduction is unlikely to be required with concomitant administration of CYP3A4 inhibitors.

Se estudia la variacion de diversos parametros fisico-quimicos del agua de un manantial ubicado en el noroeste de Espana y situado en una zona con frecuentes fuentes potenciales de contaminacion difusa, que podrian afectar a sus caracteristicas hidrologicas y causar el deterioro de la calidad del agua. A fin de conocer la variacion de la composicion del agua se efectuaron dos campanas de muestreo. Con una sonda multiparametrica se determinaron: pH, conductividad electrica, y contenidos de calcio, sodio, potasio, cloruros y nitratos. Los resultados revelan que se trata de aguas de caracter neutro, mineralizacion media y concentraciones bastante elevadas de nitratos, que ponen de manifiesto una contaminacion incipiente del agua del manantial. Todos los elementos estudiados presentan una variabilidad uniforme en el transcurso del estudio, registrandose las mayores oscilaciones en los primeros meses del mismo, lo cual parece estar relacionado con la distribucion de las precipitaciones.

This study aimed to describe types of ephemeral gullies and to determine their origin, evolution and importance as sediment sources in A Coruna province (northwest Spain). Ephemeral gullies and/or rills have been measured in a representative sample of medium-textured soils, most prone to crusting, developed over basic schist. This sample consisted of 11 small sites, ranging from 0.63 to 7.34 ha. A case study of concentrated (rill+ gully) erosion in a 0.47-ha catchment with coarse-textured soils developed over granite was also reported. The mean slope of the sites studied ranged from 6.1% to 16.8%. Main periods when soil surface was poorly covered were late spring (maize seedbeds) and late autumn-early winter (grassland and winter cereal seedbeds). Case studies where fields were left bare in winter were also investigated. Soil incision and channel formation were observed even with relatively low rainfall intensities when the soil surface was sealed, but also after a single short intense rainfall event on recently tilled surfaces. Concentrated erosion took place mainly on seedbeds and newly tilled soils in late spring and by autumn or early winter, but gullies also appeared in other seasons when the soil surface was left bare. In most of the cases studied, ephemeral gully erosion caused significant soil losses, ranging between 2 and 5 m(3)/ha for a single season to locally, over 25 m(3)/ha. Gully development was significantly affected by agricultural operations, such as lineal elements often acting as initial axes of concentrated erosion. Main gullies tended to reappear at the same position. (C) 2003 Elsevier Science B.V. All rights reserved.

This work examines the influence of various factors, such as climatic (precipitation level and flux rate) and antropogenic (soil use and management practices), on the evolution of NO3-, NO2-, NH4+ and PO43--P concentrations in the surface water of a small agricultural catchment.NH4+ and PO43- concentrations were strongly influenced by the arrival of slurries to the stream. The suspension of these fertilization practices that came with the soil use changes lead to a decrease of several orders of magnitude in their concentrations. So, NH4+ levels, after reaching peaks of 30 mg L-1 during high intensity fertilization periods, went on to be in the range 0.03 to 0.2 mg L-1 when slurry application was stopped, and PO43--P concentrations reached values of 10 mg L- and after changes in soil use showed levels above 0.3 mg L-1.Levels of NO3- and NO2- seemed to follow a different pattern. Because these compounds originate from slurry applications, they are not found in these wastes at the beginning but are created as products of a nitrification process. NO3- levels present variations ranging between 10 and 50 mg L-1, but do not undergo a strong decrease after the soil use change (six months after a change in soil use several samples reached concentrations around 60 mg L-1).In general, evaluation of the ions studied shows a low relation between ion concentrations and flux rate. Correlation coefficients calculated from NO3- data give a lower value for samples collected during the period of higher intake of slurry in the stream than when slurry addition was lower.

The majority of studies on soil fertility use experimental and statistical procedures which require statistically independent samples and uniform experimental plots. This hypothesis can only be satisfied and verified in practice with geostatistical analysis. The objective of this study was to assess and analyse the effect of land use on the spatial variability of extractable soil nutrient (Ca, Mg, K, Fe, Mn, Cu and Zn) determined by routine techniques on two adjacent fields with contrasting land uses. Point samples were collected on the surface horizon of a 190 m(2) plot, which was half cultivated and half on natural vegetation. Samples were taken on a regular 2 m x 2 m grid, with 35 points on the natural vegatation and 30 points on the cultivated area. The coefficients of skewness and kurtosis indicate that extractable nutrients didn't show normal distributions in all cases. Mean nutrient contents, with the exception of Fe, were higher in the cultivated than in the natural plot, illustrating the homogenizing and diversity-reducing effects of cultivation. Data were also analyzed by geostatistical techniques. The semivariogram show that the extracted nutrient contents did not have any variance structure (pure nugget effect), in both cultivated and natural areas. Thus, samples collected at 2 m distance can be considered as independent experiments in this area. The number of samples required to assess a mean value for extractable nutrient contents was calculated.

The spatial variability of meso- (Ca and Mg) and micronutrients (Fe, Mn, Cu, Zn, and Co) was investigated in a small cultivated plot (1.8 ha) located in the Ordenes Complex, a district of basic schists in northwest Spain. The topsoil was sampled according to a nested sampling pattern to describe the spatial variability by geostatistical techniques from 0 to about 120 m. At the sampled scale results showed that the determined meso- and micronutrients are spatially dependent; furthermore, pH, organic carbon, cation exchange capacity (CEC) and two texture fractions, namely sand and silt content, also present a distinct ordered spatial variation. The spatial structure of the studied nutrients was analyzed and variogram models with a nugget component and two spatial components with ranges of 20 and 50 m were found to fit the experimental results. Contour maps made by block kriging allowed to identify micro-regions with significantly high or low extractable nutrient contents. Micronutrient distribution appear to depend largely on organic C content, soil texture, cation exchange capacity and pH. The number of samples required to assess a mean value for extractable nutrient content was calculated. Reasonably accurate determination (i.e., 95% confidence and 20% relative error) of mean nutrient contents in a plot of this size and characteristics requires 16 to 20 samples. To reduce error due to spatial dependence, samples should be about 20 - 25 m apart.