Morphologische Untersuchungen zur formalen Pathogenese der Sialadenose menschlicher Speicheldrüsen

Besides of dental erosions, sialadenosis manifesting as bilateral swelling of parotid glands, is a typical manifestation of bulimia. Objective: The mechanism of acinar enlargement in sialadenosis is obscure, although peripheral polyneuropathy secondary to systemic disorders is assumed to be significant. This study aimed to find new aspects of pathogenesis of sialadenosis. Methods: Based on a fortuitous observation of diminished alpha-actin-positive myofilaments in myoepithelial cells in sialadenosis, 11 cases each of control and sialadenosis parotid glands were morphometrically analysed assisted by immunohistochemistry for alpha-actin, p63, cytokeratin 14 and Ki67 including double staining. Results: In sialadenosis: the acini were significantly (p<0,001) larger (1991,5 mm2 versus 1017.5 µm²); the number of myoepithelial cells as % per acinus was moderately (p= 0,005) reduced (77.2% versus 93.8%); the amount of alpha-actin-positive myofilaments as % per total circumference was significantly (p<0,001) reduced (7.2% versus 47.2%); and the proliferation rate of acinar cells was moderately (p=0,02) reduced (0.8% versus 2.0%). Conclusion: Taking into account previous ultrastructural observations of degenerative changes in peripheral nerves and in myoepithelial cells of sialadenosis our observations indicate new aspects of the pathogenesis: The loss of myofilaments of myoepithelial cells is compatible with myoepithelial insufficiency that is secondary to peripheral polyneuropathy. Possibly the resulting loss of support for the acini allows acinar secretory cells to expand. Secretory granules accumulate and produce the massive enlargement of acinar secretory cells characteristic of sialadenosis. These results might lead the ancient understanding of the pathogenesis of sialadenosis towards a new comprehension of the development of this prevalent painful disease causing „hamster cheeks“. They also promise to support the therapeutic management of complications of bulimia

Responses of Ileal and Fecal Microbiota to Withdrawal of Pancreatic Enzyme Replacement Therapy in a Porcine Model of Exocrine Pancreatic Insufficiency

Little is known regarding the interplay between microbiota and pancreas functions in humans as investigations are usually limited to distal sites, namely the analyses of fecal samples. The aim of this study was to investigate both ileal and fecal microbiota in response to pancreatic enzyme replacement therapy (PERT) in a porcine model of exocrine pancreatic insufficiency (EPI). PERT was stopped for ten days in ileo-cecal fistulated minipigs with experimentally induced EPI (n = 8) and ileal digesta as well as fecal samples were obtained before withdrawal, during withdrawal and after the reintroduction of PERT. Profound community changes occurred three days after enzyme omission and were maintained throughout the withdrawal phase. A reduction in α-diversity together with relative abundance changes in several taxa, in particular increases in Bifidobacteria (at both sites) and Lactobacilli (only feces) were observed. Overall, dysbiosis events from the ileum had accumulating effects in distal parts of the gastrointestinal tract with additional alterations occurring only in the colon. Changes were reversible after continuing PERT, and one week later, bacterial communities resembled those at baseline. Our study demonstrates the rapid and profound impacts of enzyme withdrawal in bacterial communities, contributing to our understanding of the interplay between pancreas function and microbiot