5,203 research outputs found
Contro la funzionalizzazione della contrattazione collettiva. Riflessioni sul pensiero di Mario Rusciano
No full textL'autore riflette sul pensiero di Mario Rusciano in punto di funzionalizzazione della contrattazione collettiva.The author reflects on the thought of Mario Rusciano in relation to the subject of the functionalisation of collective bargaining
Emerging therapeutic targets currently under investigation for the treatment of systemic amyloidosis
No full textPiecing together the intricate puzzle of organ recovery in AL amyloidosis
No full textIn AL amyloidosis, the factors hindering organ recovery despite deep haematological responses to anti-clonal therapy remain elusive. The study by Staron and colleagues identifies tissue-specific factors influencing the lack of organ response, including host-related characteristics, the properties of the amyloidogenic precursor, the extent of organ compromise at diagnosis and the dynamics and depth of haematological response. While this study begins to unravel the complex mechanisms underlying organ recovery in AL amyloidosis, it also raises critical questions that warrant further investigation through future collaborative research. Commentary on: Staron et al. Factors impeding organ recovery despite a deep haematological response in patients with systemic AL amyloidosis. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19766
Systemic amyloidosis: novel therapies and role of biomarkers
No full texthttps://www.ncbi.nlm.nih.gov/pubmed/2754004
The immunobiology of prion diseases
No full textIndividuals infected with prions succumb to brain damage, and prion infections continue to be inexorably lethal. However, many crucial steps in prion pathogenesis occur in lymphatic organs and precede invasion of the central nervous system. In the past two decades, a great deal has been learnt concerning the cellular and molecular mechanisms of prion lymphoinvasion. These properties are diagnostically useful and have, for example, facilitated preclinical diagnosis of variant Creutzfeldt-Jakob disease in the tonsils. Moreover, the early colonization of lymphoid organs can be exploited for post-exposure prophylaxis of prion infections. As stromal cells of lymphoid organs are crucial for peripheral prion infection, the dedifferentiation of these cells offers a powerful means of hindering prion spread in infected individuals. In this Review, we discuss the current knowledge of the immunobiology of prions with an emphasis on how basic discoveries might enable translational strategies
Altered monoaminergic systems and depressive-like behavior in congenic prion protein nnock-out mice
Full text linkCells and prions: A license to replicate
Full text linkPrion diseases are neurodegenerative, infectious disorders characterized by the aggregation of a misfolded isoform of the cellular prion protein (PrP(C)). The infectious agent - termed prion - is mainly composed of misfolded PrP(Sc). In addition to the central nervous system prions can colonize secondary lymphoid organs and inflammatory foci. Follicular dendritic cells are important extraneural sites of prion replication. However, recent data point to a broader range of cell types that can replicate prions. Here, we review the state of the art in regards to peripheral prion replication, neuroinvasion and the determinants of prion replication competence
Targeting Amyloid Fibrils by Passive Immunotherapy in Systemic Amyloidosis
No full textSystemic amyloidoses are characterized by the unrelenting deposition of autologous proteins as highly ordered fibrils in target organs. The ensuing, potentially fatal organ dysfunction is the result of the combined damage caused by the proteotoxic effect of prefibrillar species and by the cytotoxicity and the structural alterations produced by the amyloid fibrils. Current therapy is focused on eliminating the amyloid protein, thus extinguishing the amyloid cascade at its origin. While this approach may end the cell damage caused by prefibrillar aggregates and prevent further amyloid accumulation, the noxious effects of the amyloid fibrils persist and may hamper the recovery of organ function, which is the ultimate goal of therapy as it is necessary to improve the quality of life and extend survival. Preclinical studies indicate that the clearance of amyloid deposits can be accelerated by specific antibodies targeting amyloid fibrils that activate complement-mediated macrophages and giant cell phagocytosis, possibly promoting the recovery of organ function. Measuring the therapeutic effect of anti-amyloid agents is still a matter of research. In recent years, several monoclonal antibodies targeting amyloid deposits have been tested in clinical trials with mixed outcomes. Recent encouraging results from phase I/II trials, new anti-amyloid agents, and new antibody engineering offer hope that effective amyloid removal will be accomplished in the near future, accelerating organ recovery and improving quality of life and survival
The Pathophysiological and Therapeutic Implications of Cardiac Light-Chain Amyloidosis Compared With Transthyretin Amyloidosis
No full textOral Therapy for the Treatment of Transthyretin-Related Amyloid Cardiomyopathy
No full textThe care of systemic amyloidosis has improved dramatically due to improved awareness, accurate diagnostic tools, the development of powerful prognostic and companion biomarkers, and a continuous flow of innovative drugs, which translated into the blooming of phase 2/3 interventional studies for light chain (AL) and transthyretin (ATTR) amyloidosis. The unprecedented availability of effective drugs ignited great interest across various medical specialties, particularly among cardiologists who are now recognizing cardiac amyloidosis at an extraordinary pace. In all amyloidosis referral centers, we are observing a substantial increase in the prevalence of wild-type transthyretin (ATTRwt) cardiomyopathy, which is now becoming the most common form of cardiac amyloidosis. This review focuses on the oral drugs that have been recently introduced for the treatment of ATTR cardiac amyloidosis, for their ease of use in the clinic. They include both old repurposed drugs or fit-for-purpose designed compounds which bind and stabilize the TTR tetramer, thus reducing the formation of new amyloid fibrils, such as tafamidis, diflunisal, and acoramidis, as well as fibril disruptors which have the potential to promote the clearance of amyloid deposits, such as doxycycline. The development of novel therapies is based on the advances in the understanding of the molecular events underlying amyloid cardiomyopathy
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