Dipeptidyl peptidase-4 expression in pancreatic tissue from patients with congenital hyperinsulinism

Congenital hyperinsulinism (CHI) is caused by unregulated insulin release and leads to hyperinsulinaemic-hypoglycaemia (HH). Glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY (PYY) and the enzyme; dipeptidyl peptidase-4 (DPP-4) all regulate appetite and glucose homeostasis. These proteins have been identified as possible contributors to HH but the mechanism remains poorly understood. We aimed to look at the expression pattern of pancreatic DPP-4 in children with focal and diffuse CHI (FCHI and DCHI, respectively). Using immunohistochemistry; we determined DPP-4 expression patterns in the pancreas of CHI patients. DPP-4 was found to be expressed in the pancreatic β, α and δ-cells in and around the focal area. However, it was predominantly co-localised with β-cells in the paediatric tissue samples. Additionally, proliferating β-cells expressed DPP-4 in DCHI, which was absent in the FCHI pancreas. Insulin was found to be present in the exocrine acini and duct cells of the DCHI pancreas suggestive of exocrine to endocrine transdifferentiation. Furthermore, 6 medically-unresponsive DCHI pancreatic samples showed an up-regulation of total pancreatic DPP-4 expression. In conclusion; the expression studies have shown DPP-4 to be altered in HH, however, further work is required to understand the underlying role for this enzyme.     

Molecular mechanisms regulating CD13‐mediated adhesion

CD13/Aminopeptidase N is a transmembrane metalloproteinase that is expressed in many tissues where it regulates various cellular functions. In inflammation, CD13 is expressed on myeloid cells, is up‐regulated on endothelial cells at sites of inflammation and mediates monocyte/endothelial adhesion by homotypic interactions. In animal models the lack of CD13 alters the profiles of infiltrating inflammatory cells at sites of ischaemic injury. Here, we found that CD13 expression is enriched specifically on the pro‐inflammatory subset of monocytes, suggesting that CD13 may regulate trafficking and function of specific subsets of immune cells. To further dissect the mechanisms regulating CD13‐dependent trafficking we used the murine model of thioglycollate‐induced sterile peritonitis. Peritoneal monocytes, macrophages and dendritic cells were significantly decreased in inflammatory exudates from global CD13^KO animals when compared with wild‐type controls. Furthermore, adoptive transfer of wild‐type and CD13^KO primary myeloid cells, or wild‐type myeloid cells pre‐treated with CD13‐blocking antibodies into thioglycollate‐challenged wild‐type recipients demonstrated fewer CD13^KO or treated cells in the lavage, suggesting that CD13 expression confers a competitive advantage in trafficking. Similarly, both wild‐type and CD13^KO cells were reduced in infiltrates in CD13^KO recipients, confirming that both monocytic and endothelial CD13 contribute to trafficking. Finally, murine monocyte cell lines expressing mouse/human chimeric CD13 molecules demonstrated that the C‐terminal domain of the protein mediates CD13 adhesion. Therefore, this work verifies that the altered inflammatory trafficking in CD13^KO mice is the result of aberrant myeloid cell subset trafficking and further defines the molecular mechanisms underlying this regulation.     

Incidence of and Risk Factors for Hospital-Acquired Diarrhea in Three Tertiary Care Public Hospitals in Bangladesh

During April 2007–April 2010, surveillance physicians in adult and pediatric medicine wards of three tertiary public hospitals in Bangladesh identified patients who developed hospital-acquired diarrhea. We calculated incidence of hospital-acquired diarrhea. To identify risk factors, we compared these patients to randomly selected patients from the same wards who were admitted > 72 hours without having diarrhea. The incidence of hospital-acquired diarrhea was 4.8 cases per 1,000 patient-days. Children < 1 year of age were more likely to develop hospital-acquired diarrhea than older children. The risk of developing hospital-acquired diarrhea increased for each additional day of hospitalization beyond 72 hours, whereas exposure to antibiotics within 72 hours of admission decreased the risk. There were three deaths among case-patients; all were infants. Patients, particularly young children, are at risk for hospital-acquired diarrhea and associated deaths in Bangladeshi hospitals. Further research to identify the responsible organisms and transmission routes could inform prevention strategies.