Pseudomonas aeruginosa Exploits Lipid A and Muropeptides Modification as a Strategy to Lower Innate Immunity during Cystic Fibrosis Lung Infection

Pseudomonas aeruginosa can establish life-long airways chronic infection in patients with cystic fibrosis (CF) with pathogenic variants distinguished from initially acquired strain. Here, we analysed chemical and biological activity of P. aeruginosa Pathogen-Associated Molecular Patterns (PAMPs) in clonal strains, including mucoid and non-mucoid phenotypes, isolated during a period of up to 7.5 years from a CF patient. Chemical structure by MS spectrometry defined lipopolysaccharide (LPS) lipid A and peptidoglycan (PGN) muropeptides with specific structural modifications temporally associated with CF lung infection. Gene sequence analysis revealed novel mutation in pagL, which supported lipid A changes. Both LPS and PGN had different potencies when activating host innate immunity via binding TLR4 and Nod1. Significantly higher NF-kB activation, IL-8 expression and production were detected in HEK293hTLR4/MD2-CD14 and HEK293hNod1 after stimulation with LPS and PGN respectively, purified from early P. aeruginosa strain as compared to late strains. Similar results were obtained in macrophages-like cells THP-1, epithelial cells of CF origin IB3-1 and their isogenic cells C38, corrected by insertion of cystic fibrosis transmembrane conductance regulator (CFTR). In murine model, altered LPS structure of P. aeruginosa late strains induces lower leukocyte recruitment in bronchoalveolar lavage and MIP-2, KC and IL-1β cytokine levels in lung homogenates when compared with early strain. Histopathological analysis of lung tissue sections confirmed differences between LPS from early and late P. aeruginosa. Finally, in this study for the first time we unveil how P. aeruginosa has evolved the capacity to evade immune system detection, thus promoting survival and establishing favourable conditions for chronic persistence. Our findings provide relevant information with respect to chronic infections in CF

Analisi dei ricorsi avverso giudizio del Medico Competente inoltrati all'U.O.S. Prevenzione sanitaria e epidemiologia occupazionale del Servizio di prevenzione e sicurezza negli ambienti di lavoro dell'ASP di Palermo nel periodo 2008-2010

The purpose of this study is to analyze the appeals against a "suitability judgment for work" lodged to the U.O.S. "Health Prevention and Occupational Epidemiology Operative Unit" of Department of Prevention and Safety in the Working Environment within the ASP Palermo (U.O.S.), from 2008 to 2010. Studying the appeals gives an indirect view on the occupational physician activity and allows to monitor their actions, analysis aims at highlighting those issues around which any planning and implementation of coordination activities should be focused. © PI-ME, Pavia 2012

Registro degli esposti ad Agenti Biologici: analisi dell’archivio dello S.Pre.S.A.L. di Palermo nel periodo 2007-2010

In ottemperanza all’art. 280 del D.Lgs. 81/08 e s.m.i. l’ISPESL e l’Organo di Vigilanza territorialmente competente, rappresentano i destinatari dei Registri degli Esposti ad Agenti Biologici negli Ambienti di Lavoro: secondo la Normativa vigente,tali Registri vanno compilati dal datore di lavoro, con l’aiuto del Medico Competente, qualora le attività lavorative che si svolgono presso la propria azienda prevedano il contatto con microrganismi di Gruppo 3 e 4, secondo la classificazione degli agenti biologici operata dall’Art. 268 del D.Lgs. 81/08. I dati illustrati in questo studio sono stati rilevati dagli archivi dei registri pervenuti all’Unità Operativa Controllo e Vigilanza Sanitaria dello S.Pre.S.A.L. di Palermo negli anni 2007-2010. La rilevante esiguità del numero di registri pervenuti nel periodo di riferimento fa riflettere sulla notevole sottostima del numero di lavoratori esposti ad agenti biologici nel territorio della Provincia di Palermo, e offre uno spunto per intraprendere dei percorsi formativi da rivolgere ai Datori di Lavoro al fine di sensibilizzarli all’osservanza di tale adempimento