Characterization of pentoxyverine metabolites in urine using GC/MS after intoxication with Silomat cough drops.

A nearly two and a half year old boy was hospitalized after showing symptoms of disorientation and hallucination. The parents remembered the child playing with a bottle of Silomat cough drops, so that an intoxication was taken into consideration. After liquid/liquid extraction of a urine sample collected in hospital, the underivatized and the acetylated extracts were analyzed by gas chromatography-mass spectrometry (GC/MS) using electron ionization (EI) as well as chemical ionization (CI). In the urine sample high amounts of pentoxyverine (carbetapentane) and several of its metabolites, e.g., different hydrolyzed, desalkylated and ring-hydroxylated products have been identified. The correlation of the results, the observed symptoms, and the access to the Silomat cough drops reveal an intoxication after ingestion of an unknown amount of the antitussive pentoxyverine. Corresponding EI- and CI-GC/MS spectra are presented characterizing the structure of its metabolites.

Expression profiles of human 11beta-hydroxysteroid dehydrogenases type 1 and type 2 in inflammatory bowel diseases.

Inflammatory bowel diseases such as Crohn's disease (CD) and ulcerative colitis (UC) are characterized by an increase in pro-inflammatory cytokines. On the other hand, endogenous cortisol is regarded as physiological compound to combat inflammation. The local activation of glucocorticoids is mediated by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) which increases cortisol, and 11beta-HSD2 which decreases cortisol concentrations. We hypothesized that in inflamed tissues of patients suffering from inflammatory bowel diseases 11beta-HSD1 is upregulated whereas 11beta-HSD2 is downregulated. By using quantitative real-time PCR, we investigated the transcription levels of 11beta-HSD1 and 11beta-HSD2 in patients diagnosed with CD or UC. Expression of 11beta-HSD1 was significantly elevated in inflamed tissue compared to non-inflamed colonic tissue in both, CD (2.7-fold) and UC (3.8-fold), whereas 11beta-HSD2 expression was decreased in the same samples. In both diseases, male patients showed a more pronounced upregulation of 11beta-HSD1 (CD: 4.8-fold, UC: 6.5-fold) compared to females (CD: 1.8-fold, UC: 1.8-fold), a fact which might be due to the higher levels of circulating anti-inflammatory estrogens in women. Our data support the hypothesis that both enzymes play a crucial role in inflammation by affecting local tissue ratios between active and inactive glucocorticoids.