P2RX7 Purinoceptor: A Therapeutic Target for Ameliorating the Symptoms of Duchenne Muscular Dystrophy

open access articleDuchenne muscular dystrophy (DMD) is the most common inherited muscle disease, leading to severe disability and death in young men. Death is caused by the progressive degeneration of striated muscles aggravated by sterile inflammation. The pleiotropic effects of the mutant gene also include cognitive and behavioral impairments and low bone density. Current interventions in DMD are palliative only as no treatment improves the long-term outcome. Therefore, approaches with a translational potential should be investigated, and key abnormalities downstream from the absence of the DMD product, dystrophin, appear to be strong therapeutic targets. We and others have demonstrated that DMD mutations alter ATP signaling and have identified P2RX7 purinoceptor up-regulation as being responsible for the death of muscles in the mdx mouse model of DMD and human DMD lymphoblasts. Moreover, the ATP–P2RX7 axis, being a crucial activator of innate immune responses, can contribute to DMD pathology by stimulating chronic inflammation. We investigated whether ablation of P2RX7 attenuates the DMD model mouse phenotype to assess receptor suitability as a therapeutic target

Bone-marrow transplantation - Failure to correct murine muscular dystrophy

Bone-marrow cells have the potential to differentiate into other cell types such as muscle fibres, and can be transplanted into acutely or chronically damaged muscle as a way of delivering normal dystrophin (the protein that is defective or missing in Duchenne’s muscular dystrophy) to the skeletal and heart muscle of mdx mice, an animal model for this disease. But the corrective potential of this approach has been hard to estimate against the high background of muscle fibres that spontaneously revert to synthesizing dystrophin, a feature of the original mdx mutation. Here we test the long-term efficacy of bonemarrow transplantation in a different mdx mutant which is free of this problem and find that it has no impact on murine muscular dystrophy

Italian anti-Fascism in London

Impostando l'analisi sul più vasto contesto della comunità italiana di Londra negli anni Venti e sulla spaccatura esistente al suo interno tra fascisti e antifascisti, queste pagine hanno il merito di offrire un contributo originale su quella parte di antifascismo italiano nato nella capitale britannica anche come ‘contro-risposta’ all’attività di propaganda fascista sviluppata da alcuni accademici come Antonio Cippico a Camillo Pellizzi. Il contributo ricostruisce così l’impegno di uomini riconducibili a vari orientamenti politici e dottrinali, dalla massoneria, all’anarchismo, al socialismo – si ricordino tra questi Francesco Galasso, Emidio Recchioni, Giuseppe Gatti, Alessandro Magri e Paolo Treves –portando alla luce le attività di figure che sono state trascurate da precedenti studi sull’antifascismo in Gran Bretagna. Al contempo, l’indagine storica finisce per abbracciare un arco temporale alquanto ampio, dagli anni Venti fino ai Quaranta, senza dimenticare l’esperienza della seconda guerra mondiale

Italian intersociety consensus on DOAC use in internal medicine

The direct oral anticoagulants (DOACs) are drugs used in clinical practice since 2009 for the prevention of stroke or systemic embolism in non-valvular atrial fibrillation, and for the treatment and secondary prevention of venous thromboembolism. The four DOACs, including the three factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and one direct thrombin inhibitor (dabigatran) provide oral anticoagulation therapy alternatives to Vitamin K antagonists (VKAs). Despite their clear advantages, the DOACs require on the part of the internist a thorough knowledge of their pharmacokinetic and pharmacodynamic characteristics to ensure their correct use, laboratory monitoring and the appropriate management of adverse events. This document represents a consensus paper on the use of DOACs by representatives of three Italian scientific societies: the Italian Society of Internal Medicine (SIMI), the Federation of the Associations of Hospital Managers (FADOI), and the Society for the Study of Haemostasis and Thrombosis (SISET). This document formulates expert opinion guidance for pragmatic managing, monitoring and reversing the anticoagulant effect of DOACs in both chronic and emergency settings. This practical guidance may help the internist to create adequate protocols for patients hospitalized ion internal medicine wards, where patients are often elderly subjects affected by poly-morbidities and renal insufficiency, and, thus, require particular attention to drug-drug interactions and peri-procedural protocols