Archivio istituzionale della Ricerca - Università degli Studi di Parma
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Characterisation of the novel quinoline RCD405: Relaxant effects on cholinergic and histaminergic tone in human bronchi and small airways
No full textBackground and Purpose: Increased contractility of human airway smooth muscle (hASM) is a hallmark of asthma and chronic obstructive pulmonary disease (COPD). Developing new classes of bronchodilators has proved to be challenging because of efficacy and safety concerns. Quinolines hold potential therapeutic applications for the treatment of respiratory disorders. Experimental Approach: Relaxant effects of the novel quinoline RCD405 were investigated on contractile responses of hASM to carbachol, histamine and electrical field stimulation (EFS). The role of the non-adrenergic non-cholinergic (NANC) system was assessed using the inducible NO synthase inhibitor aminoguanidine and the TRPV1 agonist capsaicin. Key Results: In medium bronchi, RCD405 elicited a maximum relaxant effect (Emax) of 92 ± 4% with a half-maximal effective concentration (EC50) of 45.71 μM for carbachol, and an Emax of 96 ± 1% with a EC50 of 12 μM for histamine. In small airways, RCD405 demonstrated significant relaxant responses, with an Emax of 54 ± 7% (EC50 17 μM) for carbachol and 90 ± 6% (EC50 20 μM) for histamine. RCD405 reduced contractility in response to EFS, with Emax values of 63 ± 10% at 25 Hz and 79 ± 9% at 50 Hz in medium bronchi. The NANC system did not affect the bronchorelaxation induced by RCD405. Conclusions and Implications: RCD405 showed significant potential as a novel bronchodilator drug for the treatment of asthma and COPD through its ability to induce relaxation of hASM. These findings suggest that further investigation of RCD405 is warranted as a possible novel treatment of chronic respiratory disorders
Benchmarking Accelerometer and CNN-Based Vision Systems for Sleep Posture Classification in Healthcare Applications
No full textWhat did we learn from new treatments in SMA? A narrative review
No full textSpinal Muscular Atrophy (SMA) is a progressive neuromuscular disorder caused by SMN1 gene mutations, leading to inevitable motoneuronal degeneration. The introduction of disease modifying therapies has dramatically altered its natural history, shifting management from palliative to proactive approach. The new phenotypes and differences in treatment response and efficacy, are all contributing to reshape our understanding of the disease itself. This paper aims to analyze the lessons derived from the recent therapeutic advances, focusing on key aspects such as therapeutic windows, impact of early treatment and both disease progression and treatment efficacy modifiers. Ultimately, we also aim to give insights on new models of data analysis being explored to optimize patient trajectories and individualize treatment strategies. Our experience and the overall review of clinical trials and real-world data confirm that early treatment maximizes motor outcomes, especially when started in the pre-clinical phase of the disease. The significant clinical improvements in symptomatic type I infants treated at different ages has provided evidence of an expanded ‘therapeutic window’, previously reported as limited to the first few months after birth on the basis of neurophysiological findings. The available data also provide evidence that function at baseline, SMN2 copy number, and age at treatment all appear to represent critical determinants of response. The availability of long-term data is increasingly used to pilot new predictive models to support clinical decision-making and to adapt therapeutic goals based on patient-specific variables
Indentation and Puncturing of Pristine and Flawed Soft Membranes
No full textThis paper investigates the mechanical behavior of soft elastomeric membranes under indentation by a rigid spherical object, with a particular focus on the failure mechanisms leading to puncture. The study examines both pristine membranes and those with pre-existing flaws, such as cracks, to explore how these imperfections affect the mechanical response and failure characteristics. An analytical axisymmetric model, based on a nonlinear solution for a hyperelastic, incompressible membrane, is presented. The prediction of the model are validated with experimental data obtained from indentation tests on silicone membranes. The study considers both stretch-based and energy-based criteria for fracture, providing insight into the conditions necessary for membrane failure and crack propagation
Cardiovascular inhalation for targeted drug delivery in cardiac disease
No full textRecombinant proteins, cell, and gene therapies are collectively defined as biological drugs or biologics. These therapies have transformed the lives of millions of patients over the past decades, with the number of FDA-approved biologics increasing exponentially in recent years. However, out of approximately 700 biological therapies approved by the FDA in the last 20 years, less than 1% are indicated for cardiac pathologies. The application of biologics in cardiovascular disease has faced significant challenges, including short plasma half-life, the multifactorial complexity of cardiac disease, and the lack of efficient, non-invasive, and patient-friendly drug-delivery routes. This translational gap is particularly pressing given the immense socioeconomic burden of cardiovascular disease, which remains the leading cause of death globally and accounts for billions in annual healthcare costs and lost productivity. Inhalation-based drug delivery has recently emerged as a promising strategy for treating cardiovascular disease, with several proof-of-concept studies demonstrating its potential in heart failure, the most prevalent cardiac condition. This narrative review summarizes the latest experimental evidence in the novel field of Cardiovascular Inhalation, i.e., the lung-to-heart route for biologics. We discuss translational challenges, preclinical evidence, and future perspectives for bringing this innovative approach to clinical practice
La figura del tiranno: un'eredità antica tra pensiero greco e ricezione ciceroniana
No full textQuando si affronta la figura del tiranno, e quindi della tirannide, non si può non partire dalla consapevolezza che su tale complessa e variegata rappresentazione concettuale di una particolare condizione del politico tanto si è scritto e si continuerà a scrivere. Infatti, nel suo svolgersi in ogni epoca, nell'ambito della filosofia politica come in quello del pensiero politico occidentali, proprio la figura del tiranno ha catalizzato attorno a sé significati la cui lettura spesso travalica lo specifico aspetto del momento storico, nella sua fattualità, per connotarsi di meta-significati e di meta-funzioni che sul piano semantico la collocano in una costante metamorfosi simbolico-funzionale, sia sul piano ideologico-politico che su quello socio-culturale.
Il contributo si propone di ripercorrere alcuni dei tratti essenziali della genealogia dell’evoluzione semantico-concettuale della figura del tiranno nel mondo antico, greco e romano; data l’ampiezza del tema e delle fonti a disposizione, si cercherà di delinearne in sintesi i tratti peculiari che ne connoteranno l’immagine in chiave negativa all’interno del pensiero politico occidentale. Questo attraverso l’analisi di passi scelti dalle opere di alcuni autori “classici” appartenenti all’ambito della cultura greca, mentre per la cultura latina uno specifico approfondimento sarà dedicato alla presenza dell’immagine/figura del tiranno nell’opera di Cicerone la cui elaborazione/restituzione rimarrà paradigmatica nei secoli successivi nella trattatistica antitirannica e più in generale negli ambiti della filosofia politica e della storia del pensiero politico
“Walter Scott’s Troubadours and Post-Napoleonic Europe in The Talisman and Anne of Geierstein”
No full textReappraising the presence of the troubadour and troubadour
discourse in Romantic-period literature and culture, this essay specifically
explores Walter Scott’s re-elaborations of the troubadour theme in his output
from the Napoleonic aftermath to his final years, particularly The Talisman
(1825) and Anne of Geierstein (1829). After outlining Romantic scholarly, critical,
and creative investments in Old Occitan literature, it considers Scott’s views
of 1820s Europe and how his troubadour interests relate to his concerns with
the continent’s political situation. It subsequently analyzes the troubadour
theme in The Talisman and Anne of Geierstein in light of Scott’s reflections on
past and present-day Europe as an unstable geo-political and literary-cultural
nexus informed by contending national and transnational tendencies. As
this essay demonstrates, more than mere objects of erudition or features of
historical color, Scott’s troubadours play a significant role in the darkening
vision of post-Napoleonic Europe he developed in his later years
