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Paolo Frisoni
Department of Medical Sciences, University of Ferrara, Ferrara, Italy

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Original article
Published: 31 August 2021 in Forensic Science, Medicine and Pathology
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This study involves the histological analysis of samples taken during autopsies in cases of COVID-19 related death to evaluate the inflammatory cytokine response and the tissue localization of the virus in various organs. In all the selected cases, SARS-CoV-2 RT-PCR on swabs collected from the upper (nasopharynx and oropharynx) and/or the lower respiratory (trachea and primary bronchi) tracts were positive. Tissue localization of SARS-CoV-2 was detected using antibodies against the nucleoprotein and the spike protein. Overall, we tested the hypothesis that the overexpression of proinflammatory cytokines plays an important role in the development of COVID-19-associated pneumonia by estimating the expression of multiple cytokines (IL-1β, IL-6, IL-10, IL-15, TNF-α, and MCP-1), inflammatory cells (CD4, CD8, CD20, and CD45), and fibrinogen. Immunohistochemical staining showed that endothelial cells expressed IL-1β in lung samples obtained from the COVID-19 group (p < 0.001). Similarly, alveolar capillary endothelial cells showed strong and diffuse immunoreactivity for IL-6 and IL-15 in the COVID-19 group (p < 0.001). TNF-α showed a higher immunoreactivity in the COVID-19 group than in the control group (p < 0.001). CD8 + T cells where more numerous in the lung samples obtained from the COVID-19 group (p < 0.001). Current evidence suggests that a cytokine storm is the major cause of acute respiratory distress syndrome (ARDS) and multiple organ failure and is consistently linked with fatal outcomes.

ACS Style

Paolo Frisoni; Margherita Neri; Stefano D’Errico; Letizia Alfieri; Diana Bonuccelli; Mariano Cingolani; Marco Di Paolo; Rosa Maria Gaudio; Maurizio Lestani; Matteo Marti; Massimo Martelloni; Carlo Moreschi; Alessandro Santurro; Matteo Scopetti; Ombretta Turriziani; Martina Zanon; Roberto Scendoni; Paola Frati; Vittorio Fineschi. Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1β, IL-6, IL-15 and TNF-α. Forensic Science, Medicine and Pathology 2021, 1 -15.

AMA Style

Paolo Frisoni, Margherita Neri, Stefano D’Errico, Letizia Alfieri, Diana Bonuccelli, Mariano Cingolani, Marco Di Paolo, Rosa Maria Gaudio, Maurizio Lestani, Matteo Marti, Massimo Martelloni, Carlo Moreschi, Alessandro Santurro, Matteo Scopetti, Ombretta Turriziani, Martina Zanon, Roberto Scendoni, Paola Frati, Vittorio Fineschi. Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1β, IL-6, IL-15 and TNF-α. Forensic Science, Medicine and Pathology. 2021; ():1-15.

Chicago/Turabian Style

Paolo Frisoni; Margherita Neri; Stefano D’Errico; Letizia Alfieri; Diana Bonuccelli; Mariano Cingolani; Marco Di Paolo; Rosa Maria Gaudio; Maurizio Lestani; Matteo Marti; Massimo Martelloni; Carlo Moreschi; Alessandro Santurro; Matteo Scopetti; Ombretta Turriziani; Martina Zanon; Roberto Scendoni; Paola Frati; Vittorio Fineschi. 2021. "Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1β, IL-6, IL-15 and TNF-α." Forensic Science, Medicine and Pathology , no. : 1-15.

Journal article
Published: 16 August 2021 in International Journal of Molecular Sciences
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4,4’-Dimethylaminorex (4,4’-DMAR) is a new synthetic stimulant, and only a little information has been made available so far regarding its pharmaco-toxicological effects. The aim of this study was to investigate the effects of the systemic administration of both the single (±)cis (0.1–60 mg/kg) and (±)trans (30 and 60 mg/kg) stereoisomers and their co-administration (e.g., (±)cis at 1, 10 or 60 mg/kg + (±)trans at 30 mg/kg) in mice. Moreover, we investigated the effect of 4,4′-DMAR on the expression of markers of oxidative/nitrosative stress (8-OHdG, iNOS, NT and NOX2), apoptosis (Smac/DIABLO and NF-κB), and heat shock proteins (HSP27, HSP70, HSP90) in the cerebral cortex. Our study demonstrated that the (±)cis stereoisomer dose-dependently induced psychomotor agitation, sweating, salivation, hyperthermia, stimulated aggression, convulsions and death. Conversely, the (±)trans stereoisomer was ineffective whilst the stereoisomers’ co-administration resulted in a worsening of the toxic (±)cis stereoisomer effects. This trend of responses was confirmed by immunohistochemical analysis on the cortex. Finally, we investigated the potentially toxic effects of stereoisomer co-administration by studying urinary excretion. The excretion study showed that the (±)trans stereoisomer reduced the metabolism of the (±)cis form and increased its amount in the urine, possibly reflecting its increased plasma levels and, therefore, the worsening of its toxicity.

ACS Style

Micaela Tirri; Paolo Frisoni; Sabrine Bilel; Raffaella Arfè; Claudio Trapella; Anna Fantinati; Giorgia Corli; Beatrice Marchetti; Fabio De-Giorgio; Cristian Camuto; Monica Mazzarino; Rosa Maria Gaudio; Giovanni Serpelloni; Fabrizio Schifano; Francesco Botrè; Matteo Marti. Worsening of the Toxic Effects of (±)Cis-4,4′-DMAR Following Its Co-Administration with (±)Trans-4,4′-DMAR: Neuro-Behavioural, Physiological, Immunohistochemical and Metabolic Studies in Mice. International Journal of Molecular Sciences 2021, 22, 8771 .

AMA Style

Micaela Tirri, Paolo Frisoni, Sabrine Bilel, Raffaella Arfè, Claudio Trapella, Anna Fantinati, Giorgia Corli, Beatrice Marchetti, Fabio De-Giorgio, Cristian Camuto, Monica Mazzarino, Rosa Maria Gaudio, Giovanni Serpelloni, Fabrizio Schifano, Francesco Botrè, Matteo Marti. Worsening of the Toxic Effects of (±)Cis-4,4′-DMAR Following Its Co-Administration with (±)Trans-4,4′-DMAR: Neuro-Behavioural, Physiological, Immunohistochemical and Metabolic Studies in Mice. International Journal of Molecular Sciences. 2021; 22 (16):8771.

Chicago/Turabian Style

Micaela Tirri; Paolo Frisoni; Sabrine Bilel; Raffaella Arfè; Claudio Trapella; Anna Fantinati; Giorgia Corli; Beatrice Marchetti; Fabio De-Giorgio; Cristian Camuto; Monica Mazzarino; Rosa Maria Gaudio; Giovanni Serpelloni; Fabrizio Schifano; Francesco Botrè; Matteo Marti. 2021. "Worsening of the Toxic Effects of (±)Cis-4,4′-DMAR Following Its Co-Administration with (±)Trans-4,4′-DMAR: Neuro-Behavioural, Physiological, Immunohistochemical and Metabolic Studies in Mice." International Journal of Molecular Sciences 22, no. 16: 8771.

Journal article
Published: 25 July 2019 in Toxins
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Oleander (Nerium oleander) is an ornamental plant common in tropical and sub-tropical regions that is becoming increasingly widespread, even in temperate regions. Oleander poisoning may occur in animals and humans. The main active components contained in the plant are cardiac glycosides belonging to the class of cardenolides that are toxic to many species, from human to insects. This work describes a case of oleander poisoning that occurred on a small cattle farm and resulted in the fatality of all six resident animals. Furthermore, the investigation of the poisonous agent is described, with particular focus on the characterization of the oleandrin toxin that was recovered from the forage and rumen contents. The innovation of this study is the first description of the detection and quantification of the oleandrin toxin by liquid chromatography-high resolution mass spectrometry (LC-HRMS) in rumen.

ACS Style

Silva Rubini; Sabina Strano Rossi; Serena Mestria; Sara Odoardi; Sara Chendi; Andrea Poli; Giuseppe Merialdi; Giuseppina Andreoli; Paolo Frisoni; Rosa Maria Gaudio; Anna Baldisserotto; Piergiacomo Buso; Stefano Manfredini; Guido Govoni; Stefania Barbieri; Cinzia Centelleghe; Giorgia Corazzola; Sandro Mazzariol; Carlo Alessandro Locatelli; Poli; Buso. A Probable Fatal Case of Oleander (Nerium oleander) Poisoning on a Cattle Farm: A New Method of Detection and Quantification of the Oleandrin Toxin in Rumen. Toxins 2019, 11, 442 .

AMA Style

Silva Rubini, Sabina Strano Rossi, Serena Mestria, Sara Odoardi, Sara Chendi, Andrea Poli, Giuseppe Merialdi, Giuseppina Andreoli, Paolo Frisoni, Rosa Maria Gaudio, Anna Baldisserotto, Piergiacomo Buso, Stefano Manfredini, Guido Govoni, Stefania Barbieri, Cinzia Centelleghe, Giorgia Corazzola, Sandro Mazzariol, Carlo Alessandro Locatelli, Poli, Buso. A Probable Fatal Case of Oleander (Nerium oleander) Poisoning on a Cattle Farm: A New Method of Detection and Quantification of the Oleandrin Toxin in Rumen. Toxins. 2019; 11 (8):442.

Chicago/Turabian Style

Silva Rubini; Sabina Strano Rossi; Serena Mestria; Sara Odoardi; Sara Chendi; Andrea Poli; Giuseppe Merialdi; Giuseppina Andreoli; Paolo Frisoni; Rosa Maria Gaudio; Anna Baldisserotto; Piergiacomo Buso; Stefano Manfredini; Guido Govoni; Stefania Barbieri; Cinzia Centelleghe; Giorgia Corazzola; Sandro Mazzariol; Carlo Alessandro Locatelli; Poli; Buso. 2019. "A Probable Fatal Case of Oleander (Nerium oleander) Poisoning on a Cattle Farm: A New Method of Detection and Quantification of the Oleandrin Toxin in Rumen." Toxins 11, no. 8: 442.

Comparative study
Published: 01 June 2019 in International Journal of Legal Medicine
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MDPV is a synthetic cathinone illegally marketed and consumed for its psychostimulant effects, which are similar to those produced by cocaine, amphetamines, and MDMA. Clinical reports indicate that MDPV produces euphoria, increases alertness, and at high doses causes agitation, psychosis, tachycardia and hypertension, hallucinations, delirium, hyperthermia, rhabdomyolysis, and even death. In rodents, MDPV reproduces the typical physiological effects of psychostimulant drugs, demonstrating greater potency than cocaine. Nevertheless, its role in aggressive behavior has been reported but not yet experimentally confirmed. Therefore, the aim of this study was to evaluate the effects of acute and repeated MDPV (0.01–10 mg/kg i.p.) administration on aggressive behavior in mice and to compare them with those of cocaine (0.01–10 mg/kg i.p.) administration. To this purpose, the resident–intruder test in isolated mice and the spontaneous and stimulated aggressiveness tests for group-housed mice were employed. The present study shows for the first time that MDPV enhances aggressive behavior and locomotion in mice with greater potency and efficacy than cocaine treatment. Moreover, the aggressive and locomotor responses are enhanced after repeated administration, indicating that a sensitization mechanism comes into play. These results, although from preclinical investigation, are suggestive that human MDPV intake could be a problem for public health and the criminal justice system. Thus, investigation by police officers and medical staff is needed to prevent interpersonal violence induced by the consumption of synthetic cathinones.

ACS Style

Fabio De-Giorgio; Sabrine Bilel; Andrea Ossato; Micaela Tirri; Raffaella Arfè; Federica Foti; Giovanni Serpelloni; Paolo Frisoni; Margherita Neri; Matteo Marti. Acute and repeated administration of MDPV increases aggressive behavior in mice: forensic implications. International Journal of Legal Medicine 2019, 133, 1797 -1808.

AMA Style

Fabio De-Giorgio, Sabrine Bilel, Andrea Ossato, Micaela Tirri, Raffaella Arfè, Federica Foti, Giovanni Serpelloni, Paolo Frisoni, Margherita Neri, Matteo Marti. Acute and repeated administration of MDPV increases aggressive behavior in mice: forensic implications. International Journal of Legal Medicine. 2019; 133 (6):1797-1808.

Chicago/Turabian Style

Fabio De-Giorgio; Sabrine Bilel; Andrea Ossato; Micaela Tirri; Raffaella Arfè; Federica Foti; Giovanni Serpelloni; Paolo Frisoni; Margherita Neri; Matteo Marti. 2019. "Acute and repeated administration of MDPV increases aggressive behavior in mice: forensic implications." International Journal of Legal Medicine 133, no. 6: 1797-1808.

Journal article
Published: 12 March 2019 in International Journal of Molecular Sciences
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Several mechanisms underlying 3,4-Methylenedioxy-N-methylamphetamine (MDMA) neurotoxicity have been proposed, including neurochemical alterations and excitotoxicity mediated by reactive oxygen species (ROS), nitric oxide (NO), and reactive nitrogen species (RNS). However, ROS, NO, and RNS sources in the brain are not fully known. We aimed to investigate possible alterations in the expression of the ROS producer NOX enzymes (NOX2, NOX1, and NOX4), NO generators (iNOS, eNOS, and nNOS), markers of oxidative (8-hydroxy-2'-deoxyguanosine, 8OHdG), and nitrosative (3-nitrotyrosine, NT) stress, as well as the colocalization between cells positive for the dopamine transporter (DT1) and cells expressing the neuronal nuclei (NeuN) marker, in the frontal cortex of rats receiving saline or MDMA, sacrificed 6 h, 16 h, or 24 h after its administration. MDMA did not affect NOX2, NOX1, and NOX4 immunoreactivity, whereas iNOS expression was enhanced. The number of NT-positive cells was increased in MDMA-exposed animals, whereas no differences were detected in 8OHdG expression among experimental groups. MDMA and NT markers colocalized with DT1 positive cells. DT1 immunostaining was found in NeuN-positive stained cells. Virtually no colocalization was observed with microglia and astrocytes. Moreover, MDMA immunostaining was not found in NOX2-positive cells. Our results suggest that iNOS-derived nitrosative stress, but not NOX enzymes, may have a crucial role in the pathogenesis of MDMA-induced neurotoxicity, highlighting the specificity of different enzymatic systems in the development of neuropathological alterations induced by the abuse of this psychoactive compound.

ACS Style

Stefania Schiavone; Margherita Neri; Angela Bruna Maffione; Paolo Frisoni; Maria Grazia Morgese; Luigia Trabace; Emanuela Turillazzi. Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats. International Journal of Molecular Sciences 2019, 20, 1242 .

AMA Style

Stefania Schiavone, Margherita Neri, Angela Bruna Maffione, Paolo Frisoni, Maria Grazia Morgese, Luigia Trabace, Emanuela Turillazzi. Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats. International Journal of Molecular Sciences. 2019; 20 (5):1242.

Chicago/Turabian Style

Stefania Schiavone; Margherita Neri; Angela Bruna Maffione; Paolo Frisoni; Maria Grazia Morgese; Luigia Trabace; Emanuela Turillazzi. 2019. "Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats." International Journal of Molecular Sciences 20, no. 5: 1242.

Review
Published: 02 September 2018 in Brain Sciences
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Background: New Psychoactive Substances (NPS) constitute a broad range of hundreds of natural and synthetic drugs, including synthetic opioids, synthetic cannabinoids, synthetic cathinones, and other NPS classes, which were not controlled from 1961 to 1971 by the United Nations drug control conventions. Among these, synthetic opioids represent a major threat to public health. Methods: A literature search was carried out using public databases (such as PubMed, Google Scholar, and Scopus) to survey fentanyl-, fentanyl analogs-, and other synthetic opioid-related deaths. Keywords including “fentanyl”, “fentanyl analogs”, “death”, “overdose”, “intoxication”, “synthetic opioids”, “Novel Psychoactive Substances”, “MT-45”, “AH-7921”, and “U-47700” were used for the inquiry. Results: From our literature examination, we inferred the frequent implication of fentanyls and synthetic opioids in side effects, which primarily affected the central nervous system and the cardiovascular and pulmonary systems. The data showed a great variety of substances and lethal concentrations. Multidrug-related deaths appeared very common, in most reported cases. Conclusions: The investigation of the contribution of novel synthetic opioid intoxication to death should be based on a multidisciplinary approach aimed at framing each case and directing the investigation towards targeted toxicological analyses.

ACS Style

Paolo Frisoni; Erica Bacchio; Sabrine Bilel; Anna Talarico; Rosa Maria Gaudio; Mario Barbieri; Margherita Neri; Matteo Marti. Novel Synthetic Opioids: The Pathologist’s Point of View. Brain Sciences 2018, 8, 170 .

AMA Style

Paolo Frisoni, Erica Bacchio, Sabrine Bilel, Anna Talarico, Rosa Maria Gaudio, Mario Barbieri, Margherita Neri, Matteo Marti. Novel Synthetic Opioids: The Pathologist’s Point of View. Brain Sciences. 2018; 8 (9):170.

Chicago/Turabian Style

Paolo Frisoni; Erica Bacchio; Sabrine Bilel; Anna Talarico; Rosa Maria Gaudio; Mario Barbieri; Margherita Neri; Matteo Marti. 2018. "Novel Synthetic Opioids: The Pathologist’s Point of View." Brain Sciences 8, no. 9: 170.

Short communication
Published: 05 July 2018 in Forensic Science International
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Fishing activities are considered one of the most relevant threats for cetaceans and sea turtles conservation since these animals are sometimes found dead entangled in fishing gears. Currently, postmortem diagnosis is based mainly on the presence of nets and lines on the body and the related marks and injuries evident at gross examination. A more detailed and objective evidence is needed to clarify doubts cases and the diatoms technique, used in forensic human medicine, could support drowning diagnosis also in this field. Diatoms’ investigation was implemented to be applied in marine vertebrate on 8 striped (Stenella coeruleoalba) and 1 bottlenose (Tursiops truncatus) dolphins and 5 sea turtles (Caretta caretta) stranded along the Italian coastlines with a likely cause of death hypothized on necropsies carried out by veterinary pathologists. Diatoms were microscopically searched in the bone marrow collected from long bones implementing protocols used in human medicine and their presence was observed in 4 cetaceans and 2 sea turtles. Despite a clear relation between diatoms’ presence and amount and the likely cause of death was not proved due to the poor number of samples, the higher burden of diatoms was found in 3 animals deemed to be death for the interaction with human activity. Despite more studied are necessary to identify the possible relation between the cause of death and diatoms’ findings, the present study implemented this technique to be adapted to marine animals, confirming its possible application also in veterinary forensic medicine.

ACS Style

Silva Rubini; Paolo Frisoni; Chiara Russotto; Natascia Pedriali; Walter Mignone; Carla Grattarola; Federica Giorda; Alessandra Pautasso; Stefania Barbieri; Bruno Cozzi; Sandro Mazzariol; Rosa Maria Gaudio. The diatoms test in veterinary medicine: A pilot study on cetaceans and sea turtles. Forensic Science International 2018, 290, e19 -e23.

AMA Style

Silva Rubini, Paolo Frisoni, Chiara Russotto, Natascia Pedriali, Walter Mignone, Carla Grattarola, Federica Giorda, Alessandra Pautasso, Stefania Barbieri, Bruno Cozzi, Sandro Mazzariol, Rosa Maria Gaudio. The diatoms test in veterinary medicine: A pilot study on cetaceans and sea turtles. Forensic Science International. 2018; 290 ():e19-e23.

Chicago/Turabian Style

Silva Rubini; Paolo Frisoni; Chiara Russotto; Natascia Pedriali; Walter Mignone; Carla Grattarola; Federica Giorda; Alessandra Pautasso; Stefania Barbieri; Bruno Cozzi; Sandro Mazzariol; Rosa Maria Gaudio. 2018. "The diatoms test in veterinary medicine: A pilot study on cetaceans and sea turtles." Forensic Science International 290, no. : e19-e23.

Journal article
Published: 01 December 2017 in Forensic Science International: Genetics Supplement Series
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In order to test mRNAprofiling as a method toidentify aged blood stains, this work tested twosets ofblood stain samples, 50 and 60 plus-year-old respectively, on three blood specific markers HBB, ALAS2 and CD93, together with two housekeeping genes represented by ACTB and 18S-rRNA. Blood traces were also tested using HemDirect Hemoglobin test (SERATEC®) to compare results. Results: showed HBB as a very stable mRNA molecule highly suitable for the detection of old blood stains. HBB give positive results in over 80% of the 60-year-old samples and over 90% of the 50- year-old samples. All membranes were all weakly positive for blood, except for five 60 years back samples. Full STR profiles were accomplished for all blood samples. This finding proves mRNAprofiling an effective and alternative way of identifying aged bloodstains

ACS Style

M. Fabbri; M. Venturi; A. Talarico; P. Frisoni; R.M. Gaudio; M. Neri. mRNA profiling in ancient blood stains. Forensic Science International: Genetics Supplement Series 2017, 6, e500 -e503.

AMA Style

M. Fabbri, M. Venturi, A. Talarico, P. Frisoni, R.M. Gaudio, M. Neri. mRNA profiling in ancient blood stains. Forensic Science International: Genetics Supplement Series. 2017; 6 ():e500-e503.

Chicago/Turabian Style

M. Fabbri; M. Venturi; A. Talarico; P. Frisoni; R.M. Gaudio; M. Neri. 2017. "mRNA profiling in ancient blood stains." Forensic Science International: Genetics Supplement Series 6, no. : e500-e503.