101 research outputs found

    IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis

    Get PDF
    Dysregulated inflammasome activation contributes to respiratory infections and pathologic airway inflammation. Through basic and translational approaches involving murine models and human genetic epidemiology, we show here the importance of the different inflammasomes in regulating inflammatory responses in mice and humans with cystic fibrosis (CF), a life-threatening disorder of the lungs and digestive system. While both contributing to pathogen clearance, NLRP3 more than NLRC4 contributes to deleterious inflammatory responses in CF and correlates with defective NLRC4-dependent IL-1Ra production. Disease susceptibility in mice and microbial colonization in humans occurrs in conditions of genetic deficiency of NLRC4 or IL-1Ra and can be rescued by administration of the recombinant IL-1Ra, anakinra. These results indicate that pathogenic NLRP3 activity in CF could be negatively regulated by IL-1Ra and provide a proof-of-concept evidence that inflammasomes are potential targets to limit the pathological consequences of microbial colonization in CF

    A standard set of person-centred outcomes for diabetes mellitus: results of an international and unified approach

    Get PDF
    AIMS To select a core list of standard outcomes for diabetes to be routinely applied internationally, including patient-reported outcomes. METHODS We conducted a structured systematic review of outcome measures, focusing on adults with either type 1 or type 2 diabetes. This process was followed by a consensus-driven modified Delphi panel, including a multidisciplinary group of academics, health professionals and people with diabetes. External feedback to validate the set of outcome measures was sought from people with diabetes and health professionals. RESULTS The panel identified an essential set of clinical outcomes related to diabetes control, acute events, chronic complications, health service utilisation, and survival that can be measured using routine administrative data and/or clinical records. Three instruments were recommended for annual measurement of patient-reported outcome measures: the WHO Well-Being Index for psychological well-being; the depression module of the Patient Health Questionnaire for depression; and the Problem Areas in Diabetes scale for diabetes distress. A range of factors related to demographic, diagnostic profile, lifestyle, social support and treatment of diabetes were also identified for case-mix adjustment. CONCLUSIONS We recommend the standard set identified in this study for use in routine practice to monitor, benchmark and improve diabetes care. The inclusion of patient-reported outcomes enables people living with diabetes to report directly on their condition in a structured way

    Why is soluble intercellular adhesion molecule-1 related to cardiovascular mortality?

    Get PDF
    Background: Increased plasma levels of soluble adhesion molecules are associated with an increased risk of atherothrombosis. The pathophysiological mechanisms responsible for these associations are not known. The aim of the present study was to investigate the association of soluble intercellular adhesion molecule-1 (sICAM-1) concentration and risk of cardiovascular and all-cause mortality among individuals with and without type 2 diabetes. In addition, we assessed potential pathophysiological mechanisms by which sICAM-1 may promote mortality. Materials and methods: Six hundred and thirty-one subjects taken from a general population of the middle-aged and elderly participated in this prospective cohort study. Baseline data collection was performed from 1989 to 1992; subjects were followed until 1 January 2000. Results: Subjects who died had higher levels of sICAM-1 than those who survived (506(164) vs. 477(162) ng m

    Raccomandazioni per l\u2019esecuzione della Curva Standard da Carico Orale di Glucosio (OGTT) per la diagnosi di Diabete Mellito

    Get PDF
    The Oral Glucose Tolerance Test (OGTT) is a fractional method which measures the body's ability to metabolize glucose. Despite its large-scale use, the OGTT is still not appropriately performed in most of the Italian laboratories, as proven by our previous recent survey. In particular, we have provided evidence for the variability for execution of the OGTT in Italian laboratories indicating a poor tendency to standardise the procedures and the methodologies. These findings have been a stimulus to promote an effective Nationwide educational campaign, in order to standardise the procedures for the diagnosis of altered glucose metabolism and diabetes. The present document reports therefore the recommendations concerning the OGTT performed for the classification of diabetes. These recommendations do not apply to the execution of the OGTT during pregnancy for diagnosing gestational diabetes mellitus
    corecore