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Miyamoto, Ko-ichiro ; Sugawara, Yuri ; Kanoh, Shin´ichiro ; Yoshinobu, Tatsuo ; Wagner, Torsten ; Schöning, Michael Josef
The chemical imaging sensor is a semiconductor-based chemical sensor that can visualize the spatial distribution of chemical species. For the practical application of this sensor, artifacts in the chemical images due to defects of the semiconductor substrate and contamination of the sensing surface etc. have been a major problem. An image correction method was developed to eliminate the influence of nonuniformity of individual sensor plate.
Dexamethasone (DEX) is a potent and widely used anti-inflammatory and immunosuppressant glucocorticoid. It can bind and activate the pregnane X receptor (PXR), which plays a critical role as xenobiotic sensor in mammals to induce the expression of many enzymes, including cytochromes P450 in the CYP3A family. This induction results in its own metabolism. We have used a series of transgenic mouse lines, including a novel, improved humanized PXR line, to compare the induction profile of PXR-regulated drug-metabolizing enzymes after DEX administration, as well as looking at hepatic responses to rifampicin (RIF). The new humanized PXR model has uncovered further intriguing differences between the human and mouse receptors in that RIF only induced Cyp2b10 in the new humanized model. DEX was found to be a much more potent inducer of Cyp3a proteins in wild-type mice than in mice humanized for PXR. To assess whether PXR is involved in the detoxification of DEX in the liver, we analyzed the consequences of high doses of the glucocorticoid on hepatotoxicity on different PXR genetic backgrounds. We also studied these effects in an additional mouse model in which functional mouse Cyp3a genes have been deleted. These strains exhibited different sensitivities to DEX, indicating a protective role of the PXR and CYP3A proteins against the hepatotoxicity of this compound.
Heinzel, Alexander ; Schäfer, Ralf ; Müller, Hans-Wilhelm ; Schieffer, Andre ; Ingenhag, Ariane ; Eickhoff, Simon B. ; Northoff, Georg ; Franz, Matthias ; Hautzel, Hubertus
Background: One of the most prominent neurobiological models of alexithymia assumes an altered function of the anterior cingulate cortex (ACC) as the crucial neural correlate of alexithymia. So far functional imaging studies have yielded inconclusive results. Therefore, we tested this hypothesis in healthy alexithymics and nonalexithymics in an event-related fMRI study.
Methods: Thirty high- and 30 low-alexithymic right-handed male subjects (selected by the 20-item Toronto Alexithymia Scale, TAS-20) were investigated with event-related fMRI using a picture viewing paradigm. The stimuli consisted of happy, fearful and neutral facial expressions (Ekman-Friesen) as well as positive, negative and neutral pictures from the International Affective Picture System.
Results: Contrasting the high-alexithymic with the low-alexithymic group we observed increased activation of the supragenual ACC for different emotional valences as well as for different emotional stimuli. Moreover, there was a positive correlation of the ACC with the individual TAS-20 scores but no correlations with the individual Beck Depression Inventory scores. Additionally, there was no difference in activity of the amygdala.
Conclusions: We demonstrated that the supragenual ACC is constantly activated more strongly in alexithymic subjects and that this activation is related to the symptoms of alexithymia and not to associated symptoms such as depression. Therefore, our findings support the hypothesis of an altered function of the ACC in alexithymia.