Immunology in the clinic review series; focus on type 1 diabetes and viruses: how viral infections modulate beta cell function.

Type 1 diabetes mellitus (T1DM) is a multi-factorial immune-mediated disease characterized by the autoimmune destruction of insulin-producing pancreatic islet beta cells in genetically susceptible individuals. Epidemiological evidence has also documented the constant rise in the incidence of T1DM worldwide, with viral infections representing one of the candidate environmental risk factors identified by several independent studies. In fact, epidemiological data showed that T1DM incidence increases after epidemics due to enteroviruses and that enteroviral RNA can be detected in the blood of >50% of T1DM patients at the time of disease onset. Furthermore, both in-vitro and ex-vivo studies have shown that viruses can infect pancreatic beta cells with consequent effects ranging from functional damage to cell death.

Delta-cell-specific expression of hedgehog pathway Ptch1 receptor in murine and human endocrine pancreas.

BACKGROUND: Hedgehog pathway plays an important role during pancreas development, when its inactivation is crucial to assure expression of pancreatic marker genes involved in the organ formation and to assure an appropriate organogenesis. Patched1 (Ptch1) is a transmembrane receptor of hedgehog pathway which has a key role in this process. In fact, heterozygous Ptch1 mutant (ptc+/-) mice are affected by an impaired glucose tolerance accompanied by reduced islet function. In the light that the cell distribution of Ptch1 receptor within the endocrine pancreas has not yet been established, we aimed at identifying the pancreatic endocrine cell subset(s) expressing such molecule. METHODS: Double immunostaining for Ptch1 and pancreatic hormones insulin, glucagon and somatostatin on pancreatic paraffin sections of C57BL/6J mice and human non-diabetic multiorgan donors was performed and analysed using confocal microscopy. In addition, diabetes was experimentally induced in mice by intraperitoneal injection of streptozotocin. Quantitative real-time polymerase chain reaction after laser-capture microdissection of different islets from frozen pancreatic murine tissue sections was also performed. RESULTS: Ptch1 receptor was detected only in somatostatin-positive delta cells both in mice and in human pancreas; in mice its expression was not affected by streptozotocin treatment. A significant increase of Ptch1 mRNA expression levels in the islet periphery versus the islet core was observed by quantitative real-time polymerase chain reaction, in accord with immunohistochemical observations. CONCLUSION: Our data show a delta-cell-specific expression of Ptch1 receptor in murine and human pancreas.

Detection of four diabetes specific autoantibodies in a single radioimmunoassay: an innovative high-throughput approach for autoimmune diabetes screening.

Highly sensitive and specific radioimmunoassays have been validated for autoantibodies reacting with the four major autoantigens identified so far in autoimmune diabetes. However, the analysis of this large number of autoantigens has increased the costs and time necessary for complete autoantibody screenings. Our aim was to demonstrate that it is possible to detect the immunoreactivity against a combination of four different autoantigens by a single assay, this representing a rapid, low-cost first approach to evaluate humoral autoimmunity in diabetes. By using this novel multi-autoantigen radioimmunoassay (MAA), in subsequent steps we analysed 830 sera, 476 of known and 354 of unknown diabetes-specific immunoreactivity, collected from various groups of individuals including type 1 and type 2 diabetes patients, autoantibody-positive patients with a clinical diagnosis of type 2 diabetes (LADA), prediabetic subjects, individuals at risk to develop autoimmune diabetes, siblings of type 1 diabetic patients, coeliac patients and healthy control subjects. All sera reacting with one or more of the four autoantigens by single assays also resulted positive with MAA, as well as eight of 24 type 1 diabetic patients classified initially as autoantibody-negative at disease onset based on single autoantibody assays. In addition, MAA showed 92% sensitivity and 99% specificity by analysing 140 blinded sera from type 1 diabetic patients and control subjects provided in the 2010 Diabetes Autoantibody Standardization Program. MAA is the first combined method also able to evaluate, in addition to glutamic acid decarboxylase (GAD) and tyrosine phosphatase (IA)-2, insulin and islet beta-cell zinc cation efflux transporter (ZnT8) autoantibodies. It appears to be particularly appropriate as a first-line approach for large-scale population-based screenings of anti-islet autoimmunity.

[Survey of hospitalization in a mental health service during the ten- year period 1981-1990]. / Indagine sull'evento ricovero registratosi in un Servizio di Salute Mentale durante il decennio 1981-1990.

The paper reports the findings of a 10-year statistical survey of the users and activities of the Mental Health Service Of S. Giovanni in Fiore (Cosenza). The incidence of booth voluntary and TSO hospitalisation is reported in relation to users and with reference to the Centre's activity during other periods.