[Hyperpigmentation reveals Addison's disease in a pregnant woman].

A 31-year-old woman was admitted to the local department of endocrinology for control of known anti-TPO positive hypothyroidism during pregnancy. The clinician noticed a remarkable hyperpigmentation. Primary adrenal insufficiency was diagnosed and treatment with cortico- and mineralosteroids commenced. Diagnosis of primary adrenal insufficiency during pregnancy is challenging as many symptoms overlap with normal symptoms of pregnancy. The usual diagnostic criteria cannot be used due to the altered hormone concentrations during pregnancy.

Short-term tissue permeability actions of dextran sulfate sodium studied in a colon organ culture system.

Dextran sulfate sodium (DSS)-induced colitis is the most commonly used animal model for inflammatory bowel diseases. However, the precise molecular action of DSS, in particular its initial effect on the epithelial tissue permeability, is still poorly understood. In the present work, organ culture of mouse - and pig colon explants were performed for 1-2 h in the presence/absence of 2% DSS together with polar- and lipophilic fluorescent probes. Probe permeability was subsequently assessed by fluorescence microscopy. DSS rapidly increased paracellular permeability of 70-kDa dextran without otherwise affecting the overall epithelial integrity. FITC-conjugated DSS likewise permeated the epithelial barrier and strongly accumulated in nuclei of cells scattered in the lamina propria. By immunolabeling, plasma cells, T cells, macrophages, mast cells, and fibroblasts were identified as possible targets for DSS, indicating that accumulation of the polyanion in nuclei was not confined to a particular type of cell in the lamina propria. In contrast, colonocytes were rarely targeted by DSS, but as visualized by transmission electron microscopy, it induced the formation of vacuole-like structures in the intercellular space between adjacent epithelial cells. Nuclei of various cell types in the lamina propria, including both cells of the innate and adaptive immune system, are novel targets for a rapid action of DSS, and from previous in vitro studies, polyanions like DSS are known to disrupt nucleosomes by binding to the histones. We therefore propose that nuclear targeting is one way whereby DSS exerts its inflammatory action as a colitogen in animal models of inflammatory bowel diseases.

Pasteurella multocida toxin: Targeting mast cell secretory granules during kiss-and-run secretion.

Pasteurella multocida toxin (PMT), a virulence factor of the pathogenic Gram-negative bacterium P. multocida, is a 146 kDa protein belonging to the A-B class of toxins. Once inside a target cell, the A domain deamidates the α-subunit of heterotrimeric G-proteins, thereby activating downstream signaling cascades. However, little is known about how PMT selects and enters its cellular targets. We therefore studied PMT binding and uptake in porcine cultured intestinal mucosal explants to identify susceptible cells in the epithelium and underlying lamina propria. In comparison with Vibrio cholera B-subunit, a well-known enterotoxin taken up by receptor-mediated endocytosis, PMT binding to the epithelial brush border was scarce, and no uptake into enterocytes was detected by 2h, implying that none of the glycolipids in the brush border are a functional receptor for PMT. However, in the lamina propria, PMT distinctly accumulated in the secretory granules of mast cells. This also occurred at 4 °C, ruling out endocytosis, but suggestive of uptake via pores that connect the granules to the cell surface. Mast cell granules are known to secrete their contents by a "kiss-and-run" mechanism, and we propose that PMT may exploit this secretory mechanism to gain entry into this particular cell type.