Search

Tandem mass spectrometry and chromatographic techniques coupled with mass spectrometry are demonstrated to be extremely useful in independent investigations of biochemical and pharmacological compounds. The first chapter gives some insight into the theory behind the chromatographic and mass spectrometric techniques used. Cyclic nucleotides are vital components in biochemical signal transduction and regulation, and thus the enzymes which regulate their intracellular levels are of great interest as pharmacological targets. In chapter 2, fast atom bombardment - collision induced dissociation and mass analysed ion kinetic energy spectrometry is compared with electrospray - tandem mass spectrometry, in a quadrupole ion trap, for the structural characterisation of cyclic nucleotides and cyclic nucleotide analogues. These are used as site selective activators of cyclic nucleotide - dependent protein kinases. The activity of a multifunctional phosphodiesterase is analysed in chapter 3, using electrospray - tandem mass spectrometric techniques. This includes the differentiation and relative quantification of the isomeric products of the active enzyme preparation and the effect of several cyclic nucleotide binding agents on the enzyme activity. In chapter 4 mass spectrometric data is obtained for two lots of a diagnostic drug, manufactured by two distinct synthetic routes, and for a number of related substances, the aim being to help the manufacturer to optimise the synthetic process. Micro liquid chromatography - atmospheric pressure chemical ionisation - mass spectrometry proved to be the technique of choice for the screening of residues of sulphonamides in milk. In chapter 5, this technique is compared with conventional high performance liquid chromatography with atmospheric pressure chemical ionisation - mass spectrometric detection and capillary zone electrophoresis with electrospray - mass spectrometric detection. The former technique is sensitive and selective allowing the quantification and confirmation of the presence of 10 sulphonamides at levels below the regulatory levels in milk.

Neonicotinoids are the most common group of agricultural insecticides used worldwide, with seed treatments accounting for a large proportion of applications. Since neonicotinoids were introduced to the agricultural market, concerns have been raised regarding their effect on non-target organisms, and in the last 5 years avian-related research has gained momentum. However, the extent and impact of neonicotinoid exposure in free-living birds, particularly farmland communities, remains poorly understood. Here, data were collected for agricultural plant material and multiple species of farmland bird from neonicotinoid-treated fields, to assess the exposure pathway associated with seed treatments. Biological samples were obtained from 15 species of bird to measure levels of exposure and data were collected to investigate whether there were associated physiological sub-lethal effects. Long-term data sets for neonicotinoid use and bird populations were also modelled to assess the impact of seed treatments on farmland bird species over the last 21 years. Seed treatments were found to be a significant source of exposure for farmland birds. Exposure was confirmed in 9% of individuals pre-sowing, compared to 68% of individuals post-sowing, and 30% of species overall. Exposure was found to be associated with one physiological parameter, which could be detrimental to bird health. There was no consistent evidence to suggest that dietary exposure to neonicotinoid seed treatments has impacted bird populations historically, however three bird species warrant further investigation in this regard. These data suggest that current risk assessment and insecticide product safety protocols do not effectively safeguard farmland bird communities from neonicotinoid exposure during sowing, and imply that exposure may be widespread in bird communities where neonicotinoids are in use. Results obtained here highlight the need for field-based data in ecotoxicological risk assessments and should be considered in relation to any future systemic insecticide seed treatments.

Zorrilla es pionero en el proceso de doble redacción de la obra dramática (producto editorial y producto espectacular, que recogen textualmente los cuadernos para la puesta en escena). Consciente de las diversas recepciones de que 'El zapatero yel rey' será objeto, el autor procede a una cuidadosa reescritura del texto espectacular antes de entregar la pieza al editor: suprime didascalias redundantes, añade otras que describen gestos y acciones, o que ayudan a relacionar los hechos presentes con los de escenas o actos anteriores, e introduce los diálogos a través de verbos de lengua. Zorrilla is a pioneer in the process of the double editing of a play -an editorial product and a spectacular product which his notebooks to the production textually recollect. Conscious of the diverse receptions which 'El zapatero y el rey' will be subject of, the writer faces a careful restructuring of the spectacular text before handing ir to the editor. The final result is the deletion of redundant scene foot-notes, and the addition of others where gestures and actions are described, or helping to relate facts with earlier scenes or acts, and the introduction of dialogues.