Role of glutathionylation in infection and inflammation

Glutathionylation, that is, the formation of mixed disulfides between protein cysteines and glutathione (GSH) cysteines, is a reversible post-translational modification catalyzed by dierent cellular oxidoreductases, by which the redox state of the cell modulates protein function. So far, most studies on the identification of glutathionylated proteins have focused on cellular proteins, including proteins involved in host response to infection, but there is a growing number of reports showing that microbial proteins also undergo glutathionylation, with modification of their characteristics and functions. In the present review, we highlight the signaling role of GSH through glutathionylation, particularly focusing on microbial (viral and bacterial) glutathionylated proteins (GSSPs) and host GSSPs involved in the immune/inflammatory response to infection; moreover, we discuss the biological role of the process in microbial infections and related host responses

On the asymptotic derivation of Winkler-type energies from 3D elasticity

We show how bilateral, linear, elastic foundations (i.e. Winkler foundations) often regarded as heuristic, phenomenological models, emerge asymptotically from standard, linear, three-dimensional elasticity. We study the parametric asymptotics of a non-homogeneous linearly elastic bi-layer attached to a rigid substrate as its thickness vanishes, for varying thickness and stiffness ratios. By using rigorous arguments based on energy estimates, we provide a first rational and constructive justification of reduced foundation models. We establish the variational weak convergence of the three-dimensional elasticity problem to a two-dimensional one, of either a "membrane over in-plane elastic foundation", or a "plate over transverse elastic foundation". These two regimes are function of the only two parameters of the system, and a phase diagram synthesizes their domains of validity. Moreover, we derive explicit formulae relating the effective coefficients of the elastic foundation to the elastic and geometric parameters of the original three-dimensional system.Comment: 21 pages, 2 figure

A variational model for fracture and debonding of thin films under in-plane loadings

We study fracture and debonding of a thin stiff film bonded to a rigid substrate through a thin compliant layer, introducing a two-dimensional variational fracture model in brittle elasticity. Fractures are naturally distinguished between transverse cracks in the film (curves in 2D) and debonded surfaces (2D planar regions). In order to study the mechanical response of such systems under increasing loads, we formulate a dimension-reduced, rate-independent, irreversible evolution law accounting for both transverse fracture and debonding. We propose a numerical implementation based on a regularized formulation of the fracture problem via a gradient damage functional, and provide an illustration of its capabilities exploring complex crack patterns, showing a qualitative comparison with geometrically involved real life examples. Moreover, we justify the underlying dimension-reduced model in the setting of scalar-valued displacement fields by a rigorous asymptotic analysis using Γ-convergence, starting from the three-dimensional variational fracture (free-discontinuity) problem under precise scaling hypotheses on material and geometric parameters. © 2014 Elsevier Ltd

Violent and Complex Behaviors and Non-Restorative Sleep Are the Main Features of Disorders of Arousal in Adulthood: Real Picture or a More Severe Phenotype?

Disorders of arousal (DoA) are NREM parasomnias characterized by motor and emotional behaviors emerging from incomplete arousals from deep sleep. DoA are largely present in pediatric populations, a period during which they are labeled as self-limited manifestations. However, an extensive literature has shown that DoA can persist in adulthood, with different characteristics from childhood DoA. Adult DoA patients usually report excessive daily sleepiness, sleep-related violence during DoA episodes or potentially harmful behaviors, which are rare in childhood. The semeiological features of DoA episodes in adulthood may complicate differential diagnoses with other motor manifestations during sleep, in particular sleep-related hypermotor epilepsy. However, it cannot be excluded that adults with DoA attending sleep centers constitute a more severe phenotype, thus not being representative of adult DoA in the general population. Video-polysomnographic studies of DoA document a spectrum of motor patterns of different complexities, the simplest of which may often go unnoticed. Despite the different complexities of the episodes, neurophysiologic studies showed the co-existence of deep sleep and wakefulness during DoA episodes or even before their onset. These aspects make DoA an ideal model to investigate the mechanisms regulating local sleep, sleep arousal and cognitive functions including spatial and temporal orientation, attention or memory

Molecular evidence of Leishmania infantum in Ixodes ricinus ticks from dogs and cats, in Italy.

Leishmaniosis, caused by Leishmania infantum, is an endemic zoonosis in the Mediterranean basin. To date, phlebotomine sand flies are the only accepted biological vectors of Leishmania parasites to dogs and humans. The absence of the primary vector in autochthonous Leishmania outbreaks suggests a possible role of fleas or ticks as alternative vectors. In this study, 119 ticks were collected between August 2007-June 2008 and between March 2010-October 2010 from various animal species and humans living in Italian areas where canine leishmaniosis is endemic (i.e. rural areas of the North) and were tested for the presence of L. infantum DNA. Nine (7.5%) out of 119 ticks resulted PCR positive. All ticks were morphologically identified as Ixodes ricinus ticks, 3 from 1 cat, 6 from 4 dogs. To our knowledge, this is the first evidence of L. infantum DNA in ticks from cat, suggesting that the debate about the epidemiological role of ticks in canine leishmaniosis might be extended to feline leishmaniosis

Acute pancreatitis secondary to non-functioning pancreatic neuroendocrine tumor: uncommon clinical presentation. Clinical case and review of literature

I tumori neuroendocrini del pancreas (PNET) sono rari, e rappresentano <5% di tutte le neoplasie pancreatiche, suddivisi in PNET funzionanti con secrezione ormonale responsabile di sintomi specifici e PNET non funzionanti (nf-PNET) generalmente di diagnosi tardiva per la comparsa di metastasi o manifestazioni cliniche per effetti compressivi. L’approccio chirurgico è il trattamento di scelta per PNETs funzionanti, non-funzionanti di diametro superiore a 2 cm o sintomatici per disturbi da compressione. Osservazione personale. Donna di 76 anni ricoverata presso la UOC-Università-Chirurgia Ospedale “A. Fiorini” di Terracina per nausea e dolore ai quadranti addominali superiori con irradiazione dorso-lombare, insorti dopo un pasto serale. Dopo gli esami ematochimici e le indagini strumentali, è stata fatta la diagnosi di pancreatite acuta severa. Gli US convenzionali, CCT, CE-MRI ed EUS hanno mostrato una lesione di 2,8 cm di diametro nella giunzione testa-corpo del pancreas. L’esame citologico FNA non ha rilevato la presenza di cellule pancreatiche atipiche. La scintigrafia total body con Octreoscan® ha documentato un’area di ipercaptazione patologica situata in corrispondenza della neoformazione. La paziente è stata sottoposta a spleno-pancreasectomia corpo-coda. L’esame istologico ha dimostrato un nf-PNET di grado intermedio (G2) stenosante il vena lienale e stenosante il dotto di Wirsung, con pancreatite perilesionale. L’immunoistochimica ha mostrato un immunofenotipo positivo per CAM5.2, sinaptofisina (> 95%) e cromogranina (60%), con espressione di somatostatina intratumorale negativa. CONCLUSIONE: Sebbene raramente un nf-PNETS può essere la causa di grave pancreatite acuta non biliare da compressione del sistema duttale pancreatico. Nei casi in cui la PET / CT68Ga non può essere eseguita, la scintigrafia total body con Octreoscan® rimane il metodo più utilizzato per la diagnosi dei PNET e l’identificazione delle eventuali lesioni extra-pancreatiche. La cromogranina e la sinaptofisina sono confermate come marcatori specifici del differenziamento neuroendocrino.BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are uncommon, representing <5% of all pancreatic neoplasms, divided into functioning PNETs with secreted hormone cause of specific symptoms, and non-functioning PNETs (nf- PNETs) characterized by delayed diagnosis with metastases and clinical manifestations of compressive effects. Surgical approach is recommended for functioning and nf-PNETs >2 cm in diameter. CASE REPORT: A 76-year-old woman was admitted to the UOC-University-Surgery Hospital "A. Fiorini" in Terracina for nausea and pain in the upper abdominal quadrants with dorso-lumbar irradiation, arising after the evening meal. After the haematochemistry tests and the instrumental investigations, the diagnosis of acute, severe halitiasic pancreatitis was made. Conventional US, CCT, CE-MRI and EUS showed a 2.8cm diameter lesion in the head-body junction of the pancreas. FNA-cytological examination did not found the presence of atypical pancreatic cells. Total-body scintigraphy with Octreoscan® documented a pathological hypercaptation area located in correspondence with the neoformation. The patient underwent a body-tail spleno-pancreatectomy. The histological examination showed an intermediate grade (G2) nf-PNET infiltrating the lienal vein and stenosing the Wirsung duct, with perilesional pancreatitis. Immunohistochemistry showed CAM 5.2, Synaptophysin (>95%) and Chromogranin (60%) positive immunophenotype, with negative intratumoral Somatostatin expression. CONCLUSION: Although rarely, nf-PNETS may be the cause of severe non-biliary acute pancreatitis from pancreatic ductal system compression. In cases where PET/CT68Ga cannot be performed, total-body scintigraphy with Octreoscan® remains the most widely used method for the diagnosis of PNETs and the identification of extra-pancreatic lesions. Chromogranin and Synaptophysin are confirmed as specific markers of neuroendocrine differentiation. KEY WORDS: Acute pancreatitis, Chromogranin, Pancreatic neuroendocrine tumor, Synaptophysin, Somatostatin