Background and aims-The mechanism of gastrointestinal damage (mucositis) induced by cancer chemotherapy remains uncertain. The aims of this study were to define the time course and mechanism of small intestinal damage following chemotherapy in humans. Methods-Patients receiving chemotherapy underwent upper gastrointestinal endoscopy (a maximum of two per patient) with duodenal biopsy prior to chemotherapy and again at 1, 3, 5, and 16 days after chemotherapy. Tissue was taken for morphometry, disaccharidase assays, electron microscopy, and for assessment of apoptosis using the Tdt mediated dUTP-biotin nick end labelling (TUNEL) method. Villus area, crypt length, and mitotic index were measured by a microdissection technique. Results-Apoptosis increased sevenfold in intestinal crypts at one day, and villus area, crypt length, mitotic count per crypt, and enterocyte height decreased at three days after chemotherapy. Disaccharidase activities remained unchanged. Electron microscopy showed increased open tight junctions of enterocytes at day 3, consistent with more immature cells. All indices improved by 16 days. Conclusion-Small intestinal mucositis is associated with apoptosis in crypts that precedes hypoplastic villous atrophy and loss of enterocyte height. (Gut 2000;47:632-637)

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In an intensive care-supported model of gram-negative septic shock, early AKI was not associated with changes in renal blood flow, oxygen delivery, or histological appearance. Other mechanisms must contribute to septic AKI.

RCAN1 is a chromosome 21 gene that controls secretion in endocrine cells, regulates mitochondrial function, and is sensitive to oxidative stress. Regulator of calcineurin 1 (RCAN1) is also an endogenous inhibitor of the protein phosphatase calcineurin, the inhibition of which leads to hypoinsulinemia and diabetes in humans and mice. However, the presence or the role of RCAN1 in insulin-secreting β-cells and its potential role in the pathogenesis of diabetes is unknown. Hence, the aim of this study is to investigate the presence of RCAN1 in β-cells and identify its role in β-cell function. RCAN1 is expressed in mouse islets and in the cytosol of pancreatic β-cells. We find RCAN1 is a glucose-responsive gene with a 1.5-fold increase in expression observed in pancreatic islets in response to chronic hyperglycemia. The overexpression of the human RCAN1.1 isoform in mice under the regulation of its endogenous promoter causes diabetes, age-associated hyperglycemia, reduced glucose tolerance, hypoinsulinemia, loss of β-cells, reduced β-cell insulin secretion, aberrant mitochondrial reactive oxygen species production, and the down-regulation of key β-cell genes. Our data therefore identifies a novel molecular link between the overexpression of RCAN1 and β-cell dysfunction. The glucose-responsive nature of RCAN1 provides a potential mechanism of action associated with the β-cell dysfunction observed in diabetes.

To our knowledge, 5 cases of disseminated microsporidiosis with Encephalitozoon species have been reported worldwide in transplant recipients. George et al. present the first such case in Australia, to be reported and treated with good clinical recovery.