Successful prevalidation of the slug mucosal irritation test to assess the eye irritation potency of chemicals.

A previous 'in house' validation study showed that the SMI assay can be used as an alternative to the in vivo Draize eye irritation test. The aim of this multi-centre study with four participating laboratories was to assess the transferability and inter-laboratory variability of the assay using 20 reference chemicals covering the whole irritancy range. The eye irritation potency of the chemicals was assessed by measuring the amount of mucus produced during a 60-min contact period with a 1% dilution, and a second 60-min treatment with a 3.5% dilution. After each contact period the protein release from the mucosal surface was measured. Linear discriminant equations were used to convert the results into the corresponding EU eye irritation categories (NI, R36 and R41). All the non-irritants were predicted correctly by the four laboratories resulting in a 100% specificity. For the R36 compounds a correct classification rate of 89% (VITO) and 100% (SPL, JNJ and UGent) was obtained. The R41 compounds were classified correctly in 78% of the cases for VITO, 89% for SPL and JNJ and 100% for UGent. We can conclude that the SMI assay is a relevant, easily transferable and reproducible alternative to predict the eye irritation potency of chemicals.

Gluconeogenesis in Candida albicans.

According to different metabolic situations in various stages of Candida albicans pathogenesis the regulation of carbohydrate metabolism was investigated. We report the genetic characterization of all major C. albicans gluconeogenic and glyoxylate cycle genes (fructose-1,6-bisphosphatase, PEP carboxykinase, malate synthase and isocitrate lyase) which were isolated after functional complementation of the corresponding Saccharomyces cerevisiae deletion mutants. Remarkably, the regulation of the heterologously expressed C. albicans gluconeogenic and glyoxylate cycle genes was similar to that of the homologous S. cerevisiae genes. A C. albicans DeltaCafbp1 deletion strain failed to utilize non-fermentable carbon sources but hyphal growth was not affected. Our results show that regulation of gluconeogenesis in C. albicans is similar to that of S. cerevisiae and that the current knowledge on how gluconeogenesis is regulated will facilitate the physiological understanding of C. albicans.

False-negative findings of malignant breast lesions on preoperative magnetic resonance mammography.

The aim of this study was to evaluate causes and percentages of false negative diagnoses of malignant breast lesions on preoperative dynamic magnetic resonance mammography (MRM). MRM was performed in 223 patients with 234 histopathologically proven malignant breast lesions (193 invasive carcinoma, 41 CIS) which were analyzed prospectively by routine analysis prior to surgery and re-analyzed by specialists, retrospectively. False negative findings were re-evaluated with respect to contrast enhancement, size and shape of lesions, reading errors, and technical problems. Preoperative analysis missed 27 of 234 malignant breast lesions (sensitivity 88.5%) including 15 of 193 invasive cancers (sensitivity 92%) and 12 of 41 CIS (sensitivity 71%). Five of 193 invasive cancers (four invasive lobular, one invasive tubular carcinoma) and five of 41 CIS lesions were missed due to delayed or no contrast enhancement. The remaining 17 false negative diagnoses were due to reading errors (n=8), previous core biopsies (n=3), metal induced artefacts (n=3), localization outside the field of view (n=1), incorrect injection (n=1) or movement artefacts (n=1). Using dynamic MR mammography, there were 4.3% slow contrast enhancing malignant breast lesions and a maximum sensitivity of 95.7% for detection of all malignant breast lesions (97.4% for invasive breast cancer, 87.8% for carcinoma in situ) can be achieved in a preselected preoperative population.