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32 results on '"Fabris, Federico"'

7. Resident Esophageal Microbiota Dysbiosis Correlates with Cancer Risk in Barrett’s Esophagus Patients and Is Linked to Low Adherence to WCRF/AICR Lifestyle Recommendations

Author

Zaramella, Alice, primary, Arcidiacono, Diletta, additional, Nucci, Daniele, additional, Fabris, Federico, additional, Benna, Clara, additional, Pucciarelli, Salvatore, additional, Fassan, Matteo, additional, Fantin, Alberto, additional, De Re, Vallì, additional, Cannizzaro, Renato, additional, and Realdon, Stefano, additional

Published
2023
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10. Agonists of melatonin receptors strongly promote the functional recovery from the neuroparalysis induced by neurotoxic snakes.

Author

D'Este, Giorgia, Fabris, Federico, Stazi, Marco, Baggio, Chiara, Simonato, Morena, Megighian, Aram, Rigoni, Michela, Negro, Samuele, and Montecucco, Cesare

Subjects
*HEALTH facilities, *POISONOUS snakes, *SNAKES, *CHEMICAL agonists, *SNAKEBITES, *NEUROREHABILITATION
Abstract

Snake envenoming is a major, but neglected, tropical disease. Among venomous snakes, those inducing neurotoxicity such as kraits (Bungarus genus) cause a potentially lethal peripheral neuroparalysis with respiratory deficit in a large number of people each year. In order to prevent the development of a deadly respiratory paralysis, hospitalization with pulmonary ventilation and use of antivenoms are the primary therapies currently employed. However, hospitals are frequently out of reach for envenomated patients and there is a general consensus that additional, non-expensive treatments, deliverable even long after the snake bite, are needed. Traumatic or toxic degenerations of peripheral motor neurons cause a neuroparalysis that activates a pro-regenerative intercellular signaling program taking place at the neuromuscular junction (NMJ). We recently reported that the intercellular signaling axis melatonin-melatonin receptor 1 (MT1) plays a major role in the recovery of function of the NMJs after degeneration of motor axon terminals caused by massive Ca2+ influx. Here we show that the small chemical MT1 agonists: Ramelteon and Agomelatine, already licensed for the treatment of insomnia and depression, respectively, are strong promoters of the neuroregeneration after paralysis induced by krait venoms in mice, which is also Ca2+ mediated. The venom from a Bungarus species representative of the large class of neurotoxic snakes (including taipans, coral snakes, some Alpine vipers in addition to other kraits) was chosen. The functional recovery of the NMJ was demonstrated using electrophysiological, imaging and lung ventilation detection methods. According to the present results, we propose that Ramelteon and Agomelatine should be tested in human patients bitten by neurotoxic snakes acting presynaptically to promote their recovery of health. Noticeably, these drugs are commercially available, safe, non-expensive, have a long bench life and can be administered long after a snakebite even in places far away from health facilities. Author summary: Snakebite envenomings cause important tropical human diseases that often include a lethal muscle paralysis. Current treatments consist in hospitalization and antivenoms, which are not always quickly accessible to victims. In fact, these snakebites take place mainly in rural and low-income countries. In this work, researchers discovered, in mice, a novel function of melatonin and of its type 1 receptor in promoting functional recovery after snake-induced peripheral neuroparalysis with nerve terminal degeneration. In particular, researchers found that drugs approved for the treatment of insomnia (Ramelteon) and depression (Agomelatine), activate melatonin receptor and promote the functional recovery after a krait venom induced paralysis. These drugs are on sell in pharmacies, are safe and stable, and are ready to be tried for promoting the recovery from peripheral neuroparalysis in human victims bitten by neurotoxic snakes, even without hospitalization. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Antigen-Binding Fragments From Purified Human Monoclonal Antibodies Open to the Intrathecal Therapy of Tetanus

Author

Fabris, Federico, primary, Šoštarić, Petra, additional, Meglić, Patrik, additional, Tonellato, Marika, additional, Grinzato, Alessandro, additional, Corti, Davide, additional, Leka, Oneda, additional, Rossetto, Ornella, additional, Schiavo, Giampietro, additional, Zanotti, Giuseppe, additional, Lanzavecchia, Antonio, additional, Montecucco, Cesare, additional, Matak, Ivica, additional, and Pirazzini, Marco, additional

Published
2022
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16. FABS FROM PURIFIED HUMABS OPEN TO THE INTRATHECAL THERAPY OF TETANUS

Author

Pirazzini, Marco, Fabris, Federico, Šoštarić, Petra, Meglić, Patrik, Tonellato, Marika, Alessandro, Grinzato, Davide, Corti, Antonio, Lanzavechhia, Giampietro, Schiavo, Ornella, Rossetto, Giuseppe, Zanotti, Cesare, Montecucco, Matak, Ivica, Mršić Pelčić, Jasenka, Vitezić, Dinko, and Janković, Tamara

Subjects
FABS, TeNT
Abstract

Tetanus neurotoxin (TeNT) is the causative agent of tetanus, a fatal disease characterized by neuromuscular spastic paralysis caused by TeNT activity in inhibitory interneurons in the spinal cord. Although tetanus can be prevented using a highly effective vaccine, a worldwide clinical practice is the administration of anti- TeNT immunoglobulins (TIG) for prophylaxis and/or treatment of patients already experiencing tetanus symptoms. TIG neutralizes TeNT in peripheral body fluids before it enters peripheral nerves and is retrotransported to the spinal cord. Intrathecal administration of TIG to block TeNT at its site of action would be more effective, but this approach is limited by the low level of anti-TeNT antibodies present in TIG and the amount of protein that can be safely injected into the cerebrospinal fluid. All of these drawbacks can be overcome by highly purified human monoclonal antibodies (humAbs), which are emerging as superior therapeutics against several diseases. By screening immortalized memory B cells pooled from the blood of immunized human donors, we isolated TT104 and TT110, two humAbs that display an unprecedented neutralization ability against TeNT. We produced the Fab derivatives to determine the epitopes they recognize using cryo electron microscopy, i.e. epitopes essential for toxin binding to target neurons and light chain translocation inside the neuronal cytosol. TT104 and TT110 humAbs display in mice a prophylactic activity comparable to TIG when injected long before TeNT and the combination of TT104-Fab and TT110-Fab prevent tetanus in post exposure experiments if injected within 6 hours after TeNT, again comparably to TIG. Crucially, none of these treatments can prevent tetanus when administered later than 12 hours after TeNT inoculation, while it can be prevented by the TT104-Fab and TT110-Fab combination administered via the intrathecal route. In rats, intrathecal Fabs administered up to 24 hours after TeNT reduce the severity and duration of tetanus symptoms to a greater degree than intramuscular TIG. In conclusion, TT104 and TT110 humAbs meet all the requirements to improve the current prophylaxis and therapy of human tetanus and are ready for clinical trials while TT104- and TT110-Fab derivatives open to effective intrathecal therapy of symptomatic tetanus.

Published
2022

17. TETANUS NEUROTOXIN ACTS AT THE NEUROMUSCULAR JUNCTION AND ON BRAINSTEM CENTERS THAT CONTROL MUSCLE MOVEMENT, RESPIRATION AND SWALLOWING IN A MURINE MODEL OF CEPHALIC TETANUS

Author

Fabris, Federico, Varani, S, Tonellato, Marika, Matak, Ivica, Šoštarić, Petra, Meglić, Patrik, Simonato, Morena, Rubini, A, Caleo, Matteo, Megighian, Aram, Rossetto, Orenella, Montecucco, Cesare, Pirazzini, Marco, Mršić Pelčić, Jasenka, Vitezić, Dinko, and Janković, Tamara

Subjects
TeNT, cephalic tetanus, spasticity
Abstract

Introduction: Tetanus is a neuroparalytic syndrome caused by Tetanus Neurotoxin (TeNT), the protein exotoxin produced by Clostridium tetani. The toxin enters in the cytosol of peripheral nerves to be then retrotransported to the central nervous system, where it enters inhibitory interneurons to cleave its target VAMP, thus preventing neurotransmission and leading to spastic paralysis. One of the most dangerous and less understood form of tetanus is cephalic tetanus (CT), that begins with an unusual facial palsy, and then evolves in the canonical spastic paralysis of facial muscles, dysphagia and a rapid failure of ventilation. The contrasting symptoms often postpone the correct diagnosis, making the prognosis poor. The molecular pathogenesis of these contrasting symptoms and why CT rapidly evolves into respiratory failure remain unresolved. Materials and Methods: We developed a CT model with local injections of TeNT in different muscles of mouse’s head. We then evaluated CT molecular pathophysiology by immunofluorescence and functional analyses (whisking, ventilation). Results: We report the unexpected finding that CT facial palsy is caused by VAMP proteolysis at the neuromuscular junction. This effect shadows the canonical central effect of TeNT, which however rapidly spreads to brainstem areas controlling critical functions, including mastication, deglutition and respiration. Conclusions: In addition to elucidating the molecular bases behind the unusual CT facial palsy, we unraveled why CT can rapidly evolve in a life- threatening form of tetanus and suggest that patients presenting to the emergency room with facial nerve palsy of unknown origin should be considered for CT and immediately hospitalized

Published
2022

18. An agonist of the CXCR4 receptor is therapeutic for the neuroparalysis induced by Bungarus snakes envenoming

Author

Stazi, Marco, primary, Fabris, Federico, additional, Tan, Kae Yi, additional, Megighian, Aram, additional, Rubini, Alessandro, additional, Mattarei, Andrea, additional, Negro, Samuele, additional, D'Este, Giorgia, additional, Lista, Florigio, additional, Rossetto, Ornella, additional, Tan, Choo Hock, additional, and Montecucco, Cesare, additional

Published
2022
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21. Insulin/IGF-1 Signaling Is Downregulated in Barrett’s Esophagus Patients Undergoing a Moderate Calorie and Protein Restriction Program: A Randomized 2-Year Trial

Author

Arcidiacono, Diletta, primary, Zaramella, Alice, additional, Fabris, Federico, additional, Sánchez-Rodríguez, Ricardo, additional, Nucci, Daniele, additional, Fassan, Matteo, additional, Nardi, Mariateresa, additional, Benna, Clara, additional, Cristofori, Chiara, additional, Morbin, Tiziana, additional, Pucciarelli, Salvatore, additional, Fantin, Alberto, additional, and Realdon, Stefano, additional

Published
2021
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26. Hyperinsulinemia Promotes Esophageal Cancer Development in a Surgically-Induced Duodeno-Esophageal Reflux Murine Model

Author

Arcidiacono, Diletta, primary, Dedja, Arben, additional, Giacometti, Cinzia, additional, Fassan, Matteo, additional, Nucci, Daniele, additional, Francia, Simona, additional, Fabris, Federico, additional, Zaramella, Alice, additional, Gallagher, Emily, additional, Cassaro, Mauro, additional, Rugge, Massimo, additional, LeRoith, Derek, additional, Alberti, Alfredo, additional, and Realdon, Stefano, additional

Published
2018
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28. Local tetanus begins with a VAMP cleavage-associated neuromuscular junction paralysis around the site of tetanus neurotoxin release

Author

Fabris, Federico, Megighian, Aram, Rossetto, Ornella, Simonato, Morena, Schiavo, Giampietro, Pirazzini, Marco, and Montecucco, Cesare

Abstract

Local tetanus develops when limited amounts of tetanus neurotoxin (TeNT) are released by Clostridium tetanigenerated from spores inside a necrotic wound. Within days, a spastic paralysis restricted to the muscles of the affected anatomical area develops. This paralysis follows the retrograde transport of TeNT inside the axons of spinal cord motoneurons and its uptake by inhibitory interneurons with cleavage of VAMP, a synaptic vesicle protein required for neurotransmitter release. Consequently, incontrollable excitation of motoneurons causes contractures of innervated muscles and to local spastic paralysis.

Published
2024
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30. Reviews

Author

Kumar, Nikhil, primary, Thompson, Stephen, additional, Chauhan, Sunil, additional, Miller, James, additional, Broggi, Alicia, additional, Fraser, Robert, additional, Primorac, Ranka, additional, Roffey, Monique, additional, Das, Aurogeeta, additional, Fabris, Federico, additional, Sabbagh, Omar, additional, and McIntosh, Malachi, additional

Published
2013
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31. Spontaneous pain, pain threshold, and pain tolerance in Parkinson’s disease

Author

Zambito Marsala, Sandro, primary, Tinazzi, Michele, additional, Vitaliani, Roberta, additional, Recchia, Serena, additional, Fabris, Federico, additional, Marchini, Corrado, additional, Fiaschi, Antonio, additional, Moretto, Giuseppe, additional, Giometto, Bruno, additional, Macerollo, Antonella, additional, and Defazio, Giovanni, additional

Published
2010
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