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Orciani M.,Universit& and x00E0
Journal of biological regulators and homeostatic agents | Year: 2013

Scleroderma is a chronic systemic autoimmune disease (primarily of the skin) characterized by fibrosis (or hardening), vascular alterations and autoantibodies production.There are currently no effective therapies against this devastating and often lethal disorder. Despite the interest for the immunomodulatory effects of mesenchymal stem cells (MSCs) in autoimmune diseases, the role of MSCs in scleroderma is still unknown. A pivotal role in scleroderma onset is played by oxidative stress associated with the accumulation of great amounts of reactive oxygen species (ROS). This study depicts some phenotypic and functional features of MSCs isolated from the skin of healthy and scleroderma patients; the ROS production and accumulation, the expression of ERK1/2 and the effects of the stimulation with PDGF, were analyzed in MSCs; results were compared to those observed in primary fibroblasts (Fbs) isolated from the same subjects. We found that the pro-oxidant environment exerted by scleroderma affects MSCs, which are still able to counteract the ROS accumulation by improving the antioxidant defenses. On the contrary, scleroderma fibroblasts show a disruption of these mechanisms, with consequent ROS increase and the activation of the cascade triggered by scleroderma auto-antibodies against PDGFR.

Esposito S.,Universit& and x00E0 | Ascolese B.,Universit& and x00E0 | Senatore L.,Universit& and x00E0 | Bosis S.,Universit& and x00E0 | And 3 more authors.
International journal of immunopathology and pharmacology | Year: 2014

Mevalonate kinase deficiency (MKD) is a rare autosomal recessive autoinflammatory metabolic disease that is caused by mutations in the MVK gene. Patients with MKD typically have an early onset in infancy. MKD is characterized by recurrent episodes of high fever, abdominal distress, diffuse joint pain, and skin rashes. In a subset of patients, MKD is also associated with elevated serum immunoglobulin D (IgD) levels (hyperimmunoglobulinemia D syndrome, HIDS). The clinical phenotype of MKD varies widely and depends on the severity of the impaired mevalonate kinase activity. Complete impairment results in the severe metabolic disease, mevalonic aciduria, while a partial deficiency results in a broad spectrum of clinical presentation, including HIDS. The precise molecular mechanisms behind the elevated serum IgD levels and inflammation that occurs in MKD remain unknown. Children who exhibit symptoms of MKD should be tested for mutations in the MKD gene. However, the complexity of MKD often results in delays in its definitive diagnosis and the outcome in adult age is not completely known. Therapeutic options for MKD are based on limited data and include non-steroidal anti-inflammatory drugs, corticosteroids, and biological agents that target specific cytokine pathways. In recent years, some studies have reported promising results for new biological drugs; however, these cases have failed to achieve satisfactory remission. Therefore, further studies are needed to understand the pathogenesis of MKD and identify innovative therapeutic tools for its management.

PAOLINI L.,Universit& and x00E0 | PICCOLO M.,University of Bologna | RONCHI DELLA ROCCA S.,Universit& and x00E0
Mathematical Structures in Computer Science | Year: 2015

Intersection type assignment systems can be used as a general framework for building logical models of λ-calculus that allow to reason about the denotation of terms in a finitary way. We define essential models (a new class of logical models) through a parametric type assignment system using non-idempotent intersection types. Under an interpretation of terms based on typings instead than the usual one based on types, every suitable instance of the parameters induces a λ-model, whose theory is sensible. We prove that this type assignment system provides a logical description of a family of λ-models arising from a category of sets and relations. Copyright © Cambridge University Press 2015

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