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A specific method for the simultaneous determination of S-(+)Ibuprofen and R-(-)Ibuprofen enantiomers in human plasma is described. Adopting a high-performance liquid chromatographic (HPLC) system with spectrofluorometer detector, the compounds were extracted from plasma in alcohol medium and were separated on C18 column, using a solution of acetonitrile-water-acetic acid-triethylamine as mobile phase. The limit of quantitation was 0.1 microg/mL for both compounds. The method was validated by intra-day assays at three concentration levels and was used in a kinetic study in healthy volunteers. During the study we carried out inter-day assays to confirm the feasibility of the method.

5-Fluorouracil (5-Fu) is a commonly used anticancer agent for treatment of solid tumours. Certain studies have reported conflicting results between individual plasma concentration levels and toxicity or therapeutic effects. For this reasons some authors proposed to evaluate the plasma levels of 5-Fu metabolites 5-fluorouridine, 5-fluoro-2'-deoxyuridine and 5-fluoro-5,6-dihydro-uracil. The aim of the present work is to develop and validate a new HPLC method simultaneously determining 5-fluorouracil and its three metabolites, to be used to study the plasma levels, therapeutic effects and toxicity in cancer patients. The analytes were separated on a 4.6 x 250 mm ODS1 (5 micro m) not end-capped column, operating at room temperature. Elution was performed under isocratic conditions, employing a 1.5 mM K(3)PO(4) mobile phase (pH 5). 5-Bromo-5,6-dihydro-uracil was used as internal standard. The limits of quantitation were 0.5 micro g/mL for 5-fluorouracil, 1 micro g/mL for 5-fluoro-5,6-dihydro-uracil, 3 micro g/mL for 5-fluoro-2'-deoxyuridine and 5-fluorouridine; the stability, recovery, linearity, accuracy and specificity of the compounds were evaluated according to the criteria widely accepted. Using this method we measured plasma samples of 18 cancer patients treated with folinic acid (100 mg/m(2)) by intravenous administration, followed by an i.v. bolus of 5-Fu (400 mg/m(2)). The concentration levels of 5-fluorouracil and for 5-fluoro-5,6-dihydro-uracil were detectable in all the subjects while 5-fluorouridine and 5-fluoro-2'-deoxyuridine were present only in eight patients.

Several problems require the estimation of discrete random variables whose values can be put in a one-to-one ordered correspondence with a finite subset of the natural numbers. This happens whenever quantities are involved that represent integer items, or have been quantized on a fixed number of levels, or correspond to “graded” linguistic values. Here we propose a correct probabilistic approach to such kind of problems that fully exploits all the available prior knowledge about their own structure. In spite of the very stringent constraints induced in output space, the method can be directly applied to standard feed-forward networks while keeping local computation of both outputs and error signals. According to these guidelines, we devised a neural implementation of a complex image pre-processing algorithm by using very poor resolution on the computing elements in the network.

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Modern manufacturing processes require unambiguous description of product morphology. In spite of numerous successes in the development of new mathematical tools, there not exists a method providing complete and coherent information on the product shape along its lifecycle. Consequently, industrial methods currently employed in dimensional and geometrical controls do not fully satisfy designers, manufactures and customers. A possible solution could be a statistical description of product shape because it has strong mathematical basis, uses powerful analysis tools and provides a single unifying model along the product development process. The comparison with industrial practice and deterministic mathematical tools in the design, manufacturing and verification phases, shows some interesting advantages of the probabilistic approach. The paper illustrates the theoretical basis of the probabilistic approach, provides the instruments necessary to its implementation and, finally, shows some applications in the inspection of mechanical objects.