26 results on '"Giovanni Pecorini"'
Search Results
2. Dietary Risk Factors and Eating Behaviors in Peripheral Arterial Disease (PAD)
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Andrea Leonardo Cecchini, Federico Biscetti, Maria Margherita Rando, Elisabetta Nardella, Giovanni Pecorini, Luis H. Eraso, Paul J. Dimuzio, Antonio Gasbarrini, Massimo Massetti, and Andrea Flex
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eating behaviors ,food ,Settore MED/09 - MEDICINA INTERNA ,Organic Chemistry ,Carbohydrates ,eating disorders ,General Medicine ,Feeding Behavior ,Catalysis ,Computer Science Applications ,Diet ,Inorganic Chemistry ,Peripheral Arterial Disease ,nutrition ,predictors ,Risk Factors ,lower extremity arterial disease ,dietary risk factors ,Humans ,Physical and Theoretical Chemistry ,peripheral artery disease of lower limbs ,Molecular Biology ,Spectroscopy - Abstract
Dietary risk factors play a fundamental role in the prevention and progression of atherosclerosis and PAD (Peripheral Arterial Disease). The impact of nutrition, however, defined as the process of taking in food and using it for growth, metabolism and repair, remains undefined with regard to PAD. This article describes the interplay between nutrition and the development/progression of PAD. We reviewed 688 articles, including key articles, narrative and systematic reviews, meta-analyses and clinical studies. We analyzed the interaction between nutrition and PAD predictors, and subsequently created four descriptive tables to summarize the relationship between PAD, dietary risk factors and outcomes. We comprehensively reviewed the role of well-studied diets (Mediterranean, vegetarian/vegan, low-carbohydrate ketogenic and intermittent fasting diet) and prevalent eating behaviors (emotional and binge eating, night eating and sleeping disorders, anorexia, bulimia, skipping meals, home cooking and fast/ultra-processed food consumption) on the traditional risk factors of PAD. Moreover, we analyzed the interplay between PAD and nutritional status, nutrients, dietary patterns and eating habits. Dietary patterns and eating disorders affect the development and progression of PAD, as well as its disabling complications including major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Nutrition and dietary risk factor modification are important targets to reduce the risk of PAD as well as the subsequent development of MACE and MALE. more...
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- 2022
Catalog
3. Asthma in patients admitted to emergency department for COVID-19: prevalence and risk of hospitalization
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Gabrielli, Maurizio, Pignataro, Giulia, Candelli, Marcello, Sacco Fernandez, Marta, Bizzarri, Martina, Esperide, Alessandra, Franceschi, Francesco, Abbate, Valeria, Nicola, Acampora, Addolorato, Giovanni, Agostini, Fabiana, Ainora, Maria Elena, Akacha, Karim, Amato, Elena, Andreani, Francesca, Andriollo, Gloria, Annetta, Maria Giuseppina, Annicchiarico, Brigida Eleonora, Mariangela, Antonelli, Antonucci, Gabriele, Marco, Anzellotti Gian, Armuzzi, Alessandro, Baldi, Fabiana, Barattucci, Ilaria, Barillaro, Christian, Fabiana, Barone, Bellantone, Rocco Domenico Alfonso, Andrea, Bellieni, Bello, Giuseppe, Benicchi, Andrea, Benvenuto, Francesca, Berardini, Ludovica, Berloco, Filippo, Bernabei, Roberto, Bianchi, Antonio, Biasucci, Daniele Guerino, Biasucci, Luigi Marzio, Stefano, Bibbò, Bini, Alessandra, Alessandra, Bisanti, Biscetti, Federico, Bocci, Maria Grazia, Nicola, Bonadia, Bongiovanni, Filippo, Borghetti, Alberto, Bosco, Giulia, Bosello, Silvia Laura, Bove, Vincenzo, Bramato, Giulia, Brandi, Vincenzo, Teresa, Bruni, Bruno, Carmine, Bruno, Dario, Bungaro, Maria Chiara, Buonomo, Alessandro, Livia, Burzo, Angelo, Calabrese, Rosaria, Calvello Maria, Andrea, Cambieri, Cambise, Chiara, Camma, Giulia, Gennaro, Canistro, Antonello, Cantanale, Capalbo, Gennaro, Capaldi, Lorenzo, Capone, Emanuele, Capristo, Esmeralda, Carbone, Luigi, Silvia, Cardone, Carelli, Simone, Carfi', Angelo, Annamaria, Carnicelli, Caruso, Cristiano, Antonio, Casciaro Francesco, Catalano, Lucio, Cauda, Roberto, Cecchini, Andrea Leonardo, Cerrito, Lucia, Melania, Cesarano, Chiarito, Annalisa, Cianci, Rossella, Cicetti, Marta, Cicchinelli, Sara, Arturo, Ciccullo, Ciciarello, Francesca, Cingolani, Antonella, Cipriani, Maria Camilla, Consalvo, Ludovica Maria, Coppola, Gaetano, Corbo, Giuseppe Maria, Corsello, Andrea, Costante, Federico, Matteo, Costanzi, Covino, Marcello, Davide, Crupi, Lucio, Cutuli Salvatore, D'Addio, Stefano, D'Alessandro, Alessia, D'Alfonso, Maria Elena, D'Angelo, Emanuela, Francesca, D’Aversa, Damiano, Fernando, De Maria, Berardinis Gian, De Cunzo, Tommaso, De Gaetano Donati, Katleen, De Luca, Giulio, De Matteis, Giuseppe, De Pascale, Gennaro, De Paolo, Santis, De Martina, Siena, De Francesco, Vito, Del Valeria, Gatto, Del Paola, Giacomo, Del Fabio, Zompo, Maria, Dell’Anna Antonio, Della Davide, Polla, Di Luca, Gialleonardo, Di Simona, Giambenedetto, Di Roberta, Luca, Di Luca, Maurizio, Di Mariangela, Muro, Alex, Dusina, Davide, Eleuteri, Alessandra, Esperide, Daniele, Facheci, Domenico, Faliero, Cinzia, Falsiroli, Massimo, Fantoni, Annalaura, Fedele, Daniela, Feliciani, Cristina, Ferrante, Giuliano, Ferrone, Rossano, Festa, Chiara, Fiore Maria, Andrea, Flex, Evelina, Forte, Francesco, Franceschi, Alessandra, Francesconi, Laura, Franza, Barbara, Funaro, Mariella, Fuorlo, Domenico, Fusco, Maurizio, Gabrielli, Eleonora, Gaetani, Claudia, Galletta, Antonella, Gallo, Giovanni, Gambassi, Matteo, Garcovich, Antonio, Gasbarrini, Irene, Gasparrini, Silvia, Gelli, Antonella, Giampietro, Laura, Gigante, Gabriele, Giuliano, Giorgia, Giuliano, Bianca, Giupponi, Elisa, Gremese, Luca, Grieco Domenico, Manuel, Guerrera, Valeria, Guglielmi, Caterina, Guidone, Antonio, Gullì, Amerigo, Iaconelli, Aurora, Iafrati, Ianiro, Gianluca, Angela, Iaquinta, Michele, Impagnatiello, Riccardo, Inchingolo, Enrica, Intini, Raffaele, Iorio, Maria, Izzi Immacolata, Tamara, Jovanovic, Cristina, Kadhim, Rosa, La Macchia, Ignazio, La Milia Daniele, Francesco, Landi, Giovanni, Landi, Rosario, Landi, Raffaele, Landolfi, Massimo, Leo, Maria, Leone Paolo, Laura, Levantesi, Antonio, Liguori, Rosa, Liperoti, Maria, Lizzio Marco, Rita, Lo Monaco Maria, Pietro, Locantore, Francesco, Lombardi, Gianmarco, Lombardi, Loris, Lopetuso, Valentina, Loria, Raffaella, Losito Angela, Patricia, Lucia Mothanje Barbara, Francesco, Macagno, Noemi, Macerola, Giampaolo, Maggi, Giuseppe, Maiuro, Francesco, Mancarella, Francesca, Mangiola, Alberto, Manno, Debora, Marchesini, Marco, Maresca Gian, Giuseppe, Marrone, Ilaria, Martis, Maria, Martone Anna, Marzetti, Emanuele, Chiara, Mattana, Valeria, Matteo Maria, Riccardo, Maviglia, Ada, Mazzarella, Carmen, Memoli, Luca, Miele, Alessio, Migneco, Irene, Mignini, Alessandro, Milani, Domenico, Milardi, Massimo, Montalto, Giuliano, Montemurro, Flavia, Monti, Montini, Luca, Christian, Morena Tony, Vincenzina, Morra, Davide, Moschese, Ambra, Murace Celeste, Martina, Murdolo, Rita, Murri, Marco, Napoli, Elisabetta, Nardella, Gerlando, Natalello, Daniele, Natalini, Maria, Navarra Simone, Antonio, Nesci, Alberto, Nicoletti, Rocco, Nicoletti, Filippo, Nicoletti Tommaso, Rebecca, Nicolò, Nicola, Nicolotti, Celestino, Nista Enrico, Eugenia, Nuzzo, Marco, Oggiano, Veronica, Ojetti, Cosimo, Pagano Francesco, Gianfranco, Paiano, Cristina, Pais, Federico, Paolillo, Federico, Pallavicini, Andrea, Palombo, Alfredo, Papa, Domenico, Papanice, Giovanni, Papparella Luigi, Mattia, Paratore, Giuseppe, Parrinello, Giuliana, Pasciuto, Pierpaolo, Pasculli, Giovanni, Pecorini, Simone, Perniola, Erika, Pero, Luca, Petricca, Martina, Petrucci, Chiara, Picarelli, Andrea, Piccioni, Annalisa, Piccolo, Edoardo, Piervincenzi, Giulia, Pignataro, Raffaele, Pignataro, Gabriele, Pintaudi, Luca, Pisapia, Marco, Pizzoferrato, Fabrizio, Pizzolante, Roberto, Pola, Caterina, Policola, Maurizio, Pompili, Flavia, Pontecorvi, Valerio, Pontecorvi, Francesca, Ponziani, Valentina, Popolla, Enrica, Porceddu, Angelo, Porfidia, Maria, Porro Lucia, Annalisa, Potenza, Francesca, Pozzana, Giuseppe, Privitera, Daniela, Pugliese, Gabriele, Pulcini, Simona, Racco, Francesca, Raffaelli, Vittoria, Ramunno, Ludovico, Rapaccini Gian, Richeldi, Luca, Rinninella, Emanuele, Sara, Rocchi, Bruno, Romanò, Stefano, Romano, Federico, Rosa, Laura, Rossi, Raimondo, Rossi, Enrica, Rossini, Elisabetta, Rota, Fabiana, Rovedi, Carlotta, Rubino, Gabriele, Rumi, Andrea, Russo, Luca, Sabia, Andrea, Salerno, Sara, Salini, Lucia, Salvatore, Dehara, Samori, Sandroni, Claudio, Maurizio, Sanguinetti, Luca, Santarelli, Paolo, Santini, Danilo, Santolamazza, Angelo, Santoliquido, Francesco, Santopaolo, Cosimo, Santoro Michele, Francesco, Sardeo, Caterina, Sarnari, Angela, Saviano, Luisa, Saviano, Scaldaferri, Franco, Roberta, Scarascia, Tommaso, Schepis, Francesca, Schiavello, Giancarlo, Scoppettuolo, Davide, Sedda, Flaminio, Sessa, Luisa, Sestito, Carlo, Settanni, Matteo, Siciliano, Valentina, Siciliano, Rossella, Sicuranza, Benedetta, Simeoni, Jacopo, Simonetti, Andrea, Smargiassi, Maurizio, Soave Paolo, Chiara, Sonnino, Domenico, Staiti, Claudia, Stella, Leonardo, Stella, Eleonora, Stival, Eleonora, Taddei, Rossella, Talerico, Elio, Tamburello, Enrica, Tamburrini, Sofia, Tanzarella Eloisa, Elena, Tarascio, Claudia, Tarli, Alessandra, Tersali, Pietro, Tilli, Jacopo, Timpano, Enrico, Torelli, Flavia, Torrini, Matteo, Tosato, Alberto, Tosoni, Luca, Tricoli, Marcello, Tritto, Mario, Tumbarello, Maria, Tummolo Anita, Sole, Vallecoccia Maria, Federico, Valletta, Francesco, Varone, Francesco, Vassalli, Giulio, Ventura, Lucrezia, Verardi, Lorenzo, Vetrone, Giuseppe, Vetrugno, Elena, Visconti, Felicia, Visconti, Andrea, Viviani, Raffaella, Zaccaria, Carmelina, Zaccone, Lorenzo, Zelano, Lorenzo, Zileri Dal Verme, and Giuseppe, Zuccalà more...
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2019-20 coronavirus outbreak ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Emergency department ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,COVID-19 ,Settore MED/10 - MALATTIE DELL'APPARATO RESPIRATORIO ,asthma ,medicine.disease ,Hospitalization ,Emergency medicine ,CE-Research Letter to the Editor ,SARS-CoV2 ,Emergency Medicine ,Internal Medicine ,medicine ,Prevalence ,Humans ,In patient ,business ,Emergency Service, Hospital ,Asthma ,Retrospective Studies - Published
- 2021
4. COVID-19 and intestinal inflammation: Role of fecal calprotectin
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Veronica Ojetti, Angela Saviano, Marcello Covino, Nicola Acampora, Eliana Troiani, Francesco Franceschi, Valeria Abbate, Giovanni Addolorato, Fabiana Agostini, Maria Elena Ainora, Karim Akacha, Elena Amato, Francesca Andreani, Gloria Andriollo, Maria Giuseppina Annetta, Brigida Eleonora Annicchiarico, Mariangela Antonelli, Gabriele Antonucci, Gian Marco Anzellotti, Alessandro Armuzzi, Fabiana Baldi, Ilaria Barattucci, Christian Barillaro, Fabiana Barone, Rocco Domenico Alfonso Bellantone, Andrea Bellieni, Giuseppe Bello, Andrea Benicchi, Francesca Benvenuto, Ludovica Berardini, Filippo Berloco, Roberto Bernabei, Antonio Bianchi, Daniele Guerino Biasucci, Luigi Marzio Biasucci, Stefano Bibbò, Alessandra Bini, Alessandra Bisanti, Federico Biscetti, Maria Grazia Bocci, Nicola Bonadia, Filippo Bongiovanni, Alberto Borghetti, Giulia Bosco, Silvia Bosello, Vincenzo Bove, Giulia Bramato, Vincenzo Brandi, Teresa Bruni, Carmine Bruno, Dario Bruno, Maria Chiara Bungaro, Alessandro Buonomo, Livia Burzo, Angelo Calabrese, Maria Rosaria Calvello, Andrea Cambieri, Chiara Cambise, Giulia Cammà, Marcello Candelli, Gennaro Canistro, Antonello Cantanale, Gennaro Capalbo, Lorenzo Capaldi, Emanuele Capone, Esmeralda Capristo, Luigi Carbone, Silvia Cardone, Simone Carelli, Angelo Carfì, Annamaria Carnicelli, Cristiano Caruso, Francesco Antonio Casciaro, Lucio Catalano, Roberto Cauda, Andrea Leonardo Cecchini, Lucia Cerrito, Melania Cesarano, Annalisa Chiarito, Rossella Cianci, Sara Cicchinelli, Arturo Ciccullo, Marta Cicetti, Francesca Ciciarello, Antonella Cingolani, Maria Camilla Cipriani, Maria Ludovica Consalvo, Gaetano Coppola, Giuseppe Maria Corbo, Andrea Corsello, Federico Costante, Matteo Costanzi, Davide Crupi, Salvatore Lucio Cutuli, Stefano D'Addio, Alessia D'Alessandro, Maria ElenaEmanuela D'AlfonsoD'Angelo, Francesca D'Aversa, Fernando Damiano, Gian Maria De Berardinis, Tommaso De Cunzo, Donati Katleen De Gaetano, Giulio De Luca, Giuseppe De Matteis, Gennaro De Pascale, Paolo De Santis, Martina De Siena, Francesco De Vito, Valeria Del Gatto, Paola Del Giacomo, Fabio Del Zompo, Antonio Maria Dell'Anna, Davide Della Polla, Luca Di Gialleonardo, Simona Di Giambenedetto, Roberta Di Luca, Luca Di Maurizio, Mariangela Di Muro, Alex Dusina, Davide Eleuteri, Alessandra Esperide, Daniele Fachechi, Domenico Faliero, Cinzia Falsiroli, Massimo Fantoni, Annalaura Fedele, Daniela Feliciani, Cristina Ferrante, Giuliano Ferrone, Rossano Festa, Maria Chiara Fiore, Andrea Flex, Evelina Forte, Alessandra Francesconi, Laura Franza, Barbara Funaro, Mariella Fuorlo, Domenico Fusco, Maurizio Gabrielli, Eleonora Gaetani, Claudia Galletta, Antonella Gallo, Giovanni Gambassi, Matteo Garcovich, Antonio Gasbarrini, Irene Gasparrini, Silvia Gelli, Antonella Giampietro, Laura Gigante, Gabriele Giuliano, Giorgia Giuliano, Bianca Giupponi, Elisa Gremese, Domenico Luca Grieco, Manuel Guerrera, Valeria Guglielmi, Caterina Guidone, Antonio Gullì, Amerigo Iaconelli, Aurora Iafrati, Gianluca Ianiro, Angela Iaquinta, Michele Impagnatiello, Riccardo Inchingolo, Enrica Intini, Raffaele Iorio, Immacolata Maria Izzi, Tamara Jovanovic, Cristina Kadhim, Rosa La Macchia, Daniele Ignazio La Milia, Francesco Landi, Giovanni Landi, Rosario Landi, Raffaele Landolfi, Massimo Leo, Paolo Maria Leone, Laura Levantesi, Antonio Liguori, Rosa Liperoti, Marco Maria Lizzio, Maria Rita Lo Monaco, Pietro Locantore, Francesco Lombardi, Gianmarco Lombardi, Loris Lopetuso, Valentina Loria, Angela Raffaella Losito, Mothanje Barbara Patricia Lucia, Francesco Macagno, Noemi Macerola, Giampaolo Maggi, Giuseppe Maiuro, Francesco Mancarella, Francesca Mangiola, Alberto Manno, Debora Marchesini, Gian Marco Maresca, Giuseppe Marrone, Ilaria Martis, Anna Maria Martone, Emanuele Marzetti, Chiara Mattana, Maria Valeria Matteo, Riccardo Maviglia, Ada Mazzarella, Carmen Memoli, Luca Miele, Alessio Migneco, Irene Mignini, Alessandro Milani, Domenico Milardi, Massimo Montalto, Giuliano Montemurro, Flavia Monti, Luca Montini, Tony Christian Morena, Vincenzina Morra, Chiara Morretta, Davide Moschese, Celeste Ambra Murace, Martina Murdolo, Rita Murri, Marco Napoli, Elisabetta Nardella, Gerlando Natalello, Daniele Natalini, Simone Maria Navarra, Antonio Nesci, Alberto Nicoletti, Rocco Nicoletti, Tommaso Filippo Nicoletti, Rebecca Nicolò, Nicola Nicolotti, Enrico Celestino Nista, Eugenia Nuzzo, Marco Oggiano, Francesco Cosimo Pagano, Gianfranco Paiano, Cristina Pais, Federico Pallavicini, Andrea Palombo, Federico Paolillo, Alfredo Papa, Domenico Papanice, Luigi Giovanni Papparella, Mattia Paratore, Giuseppe Parrinello, Giuliana Pasciuto, Pierpaolo Pasculli, Giovanni Pecorini, Simone Perniola, Erika Pero, Luca Petricca, Martina Petrucci, Chiara Picarelli, Andrea Piccioni, Annalisa Piccolo, Edoardo Piervincenzi, Giulia Pignataro, Raffaele Pignataro, Gabriele Pintaudi, Luca Pisapia, Marco Pizzoferrato, Fabrizio Pizzolante, Roberto Pola, Caterina Policola, Maurizio Pompili, Flavia Pontecorvi, Valerio Pontecorvi, Francesca Ponziani, Valentina Popolla, Enrica Porceddu, Angelo Porfidia, Lucia Maria Porro, Annalisa Potenza, Francesca Pozzana, Giuseppe Privitera, Daniela Pugliese, Gabriele Pulcini, Simona Racco, Francesca Raffaelli, Vittoria Ramunno, Gian Ludovico Rapaccini, Luca Richeldi, Emanuele Rinninella, Sara Rocchi, Bruno Romanò, Stefano Romano, Federico Rosa, Laura Rossi, Raimondo Rossi, Enrica Rossini, Elisabetta Rota, Fabiana Rovedi, Carlotta Rubino, Gabriele Rumi, Andrea Russo, Luca Sabia, Andrea Salerno, Sara Salini, Lucia Salvatore, Dehara Samori, Claudio Sandroni, Maurizio Sanguinetti, Luca Santarelli, Paolo Santini, Danilo Santolamazza, Angelo Santoliquido, Francesco Santopaolo, Michele Cosimo Santoro, Francesco Sardeo, Caterina Sarnari, Luisa Saviano, Franco Scaldaferri, Roberta Scarascia, Tommaso Schepis, Francesca Schiavello, Giancarlo Scoppettuolo, Davide Sedda, Flaminio Sessa, Luisa Sestito, Carlo Settanni, Matteo Siciliano, Valentina Siciliano, Rossella Sicuranza, Benedetta Simeoni, Jacopo Simonetti, Andrea Smargiassi, Paolo Maurizio Soave, Chiara Sonnino, Domenico Staiti, Claudia Stella, Leonardo Stella, Eleonora Stival, Eleonora Taddei, Rossella Talerico, Elio Tamburello, Enrica Tamburrini, Eloisa Sofia Tanzarella, Elena Tarascio, Claudia Tarli, Alessandra Tersali, Pietro Tilli, Jacopo Timpano, Enrico Torelli, Flavia Torrini, Matteo Tosato, Alberto Tosoni, Luca Tricoli, Marcello Tritto, Mario Tumbarello, Anita Maria Tummolo, Maria Sole Vallecoccia, Federico Valletta, Francesco Varone, Francesco Vassalli, Giulio Ventura, Lucrezia Verardi, Lorenzo Vetrone, Giuseppe Vetrugno, Elena Visconti, Felicia Visconti, Andrea Viviani, Raffaella Zaccaria, Carmelina Zaccone, Lorenzo Zelano, Lorenzo Zileri Dal Verme, and Giuseppe Zuccalà more...
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Adult ,Male ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Settore MED/12 - GASTROENTEROLOGIA ,Pneumonia, Viral ,Severity of Illness Index ,Gastroenterology ,Betacoronavirus ,Feces ,Intestinal mucosa ,Intestinal inflammation ,Internal medicine ,Settore MED/41 - ANESTESIOLOGIA ,medicine ,Humans ,Viral ,Intestinal Mucosa ,Letter to the Editor ,Pandemics ,Leukocyte L1 Antigen Complex ,Hepatology ,SARS-CoV-2 ,business.industry ,Settore MED/09 - MEDICINA INTERNA ,COVID-19 ,Pneumonia ,Middle Aged ,fecal calprotectin ,Case-Control Studies ,Female ,Calprotectin ,Coronavirus Infections ,business ,Biomarkers - Published
- 2020
5. High mobility group box-1 and diabetes mellitus complications: State of the art and future perspectives
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Federico Biscetti, Maria Margherita Rando, Andrea Leonardo Cecchini, Elisabetta Nardella, Giovanni Pecorini, Raffaele Landolfi, and Andrea Flex
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0301 basic medicine ,medicine.medical_specialty ,Ischemia ,Review ,030204 cardiovascular system & hematology ,HMGB1 ,Models, Biological ,Catalysis ,Inorganic Chemistry ,Sepsis ,Diabetes Complications ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Models ,medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,HMGB1 Protein ,Intensive care medicine ,Molecular Biology ,Pathological ,High Mobility Group Box-1 (HMGB1) ,Spectroscopy ,Endemic disease ,biology ,business.industry ,Organic Chemistry ,Settore MED/09 - MEDICINA INTERNA ,Vascular complications ,General Medicine ,medicine.disease ,Biological ,3. Good health ,Computer Science Applications ,030104 developmental biology ,biology.protein ,business ,Diabetes Mellitus Complications - Abstract
Diabetes mellitus (DM) is an endemic disease, with growing health and social costs. The complications of diabetes can affect potentially all parts of the human body, from the heart to the kidneys, peripheral and central nervous system, and the vascular bed. Although many mechanisms have been studied, not all players responsible for these complications have been defined yet. High Mobility Group Box-1 (HMGB1) is a non-histone nuclear protein that has been implicated in many pathological processes, from sepsis to ischemia. The purpose of this review is to take stock of all the most recent data available on the role of HMGB1 in the complications of DM. more...
- Published
- 2019
6. Fever of unknown origin and splenomegaly: A case report of blood culture negative endocarditis
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Mariangela Antonelli, Maria Livia Burzo, Angela Favuzzi, Andrea Flex, Giovanni Pecorini, and Raffaele Landolfi
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Aortic valve ,Bartonella ,medicine.medical_specialty ,Fever ,030204 cardiovascular system & hematology ,Transesophageal echocardiogram ,Real-Time Polymerase Chain Reaction ,Fever of Unknown Origin ,Serology ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Endocarditis ,Humans ,030212 general & internal medicine ,Clinical Case Report ,Fever of unknown origin ,biology ,medicine.diagnostic_test ,business.industry ,Settore MED/09 - MEDICINA INTERNA ,Cat-Scratch Disease ,General Medicine ,Endocarditis, Bacterial ,Middle Aged ,medicine.disease ,biology.organism_classification ,Valvular disease ,Combined Modality Therapy ,echocardiogram ,Anti-Bacterial Agents ,Stenosis ,medicine.anatomical_structure ,Echocardiography ,Splenomegaly ,Gentamicin ,Female ,business ,medicine.drug ,Research Article - Abstract
Rationale: Fever of unknown origin (FUO) can be determined by different conditions among which infectious diseases represent the main cause. Patient concerns: A young woman, with a history of aortic stenosis, was admitted to our unit for a month of intermittent fever associated with a new diastolic heart murmur and splenomegaly. Laboratory tests were negative for infectious screening. The total body computed tomography (CT) scan excluded abscesses, occulted neoplasia, or lymphadenopathy. Diagnoses: The transthoracic and transesophageal echocardiogram showed an aortic valve vegetation. Three sets of blood cultures were negative for all microorganisms tested. According to these findings, Bartonella endocarditis was suspected and the serology tests performed were positive. Finally, real-time polymerase chain reaction (RT-PCR) detected Bartonella henselae DNA on tissue valve. Interventions: The patient underwent heart valve surgery and a treatment of Ampicillin, Gentamicin, and oral Doxycycline was prescribed for 16 days and, successively, with Doxycycline and Ceftriaxone for 6 weeks. Outcomes: After surgery and antibiotic therapy, patient continued to do well. Lessons: Bartonella species are frequently the cause of negative blood culture endocarditis. Molecular biology techniques are the only useful tool for diagnosis. Valvular replacement is often necessary and antibiotic regimen with Gentamicin and either Ceftriaxone or Doxycycline is suggested as treatment. Echocardiogram and blood cultures must be performed in all cases of FUO. When blood cultures are negative and echocardiographic tools are indicative, early use of Bartonella serology is recommended. more...
- Published
- 2017
7. Association between TNFRSF11B gene polymorphisms and history of ischemic stroke in Italian diabetic patients
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Angelo Santoliquido, Carlo Filippo Porreca, Silvia Giovannini, Andrea Flex, Federico Biscetti, Giuseppe Straface, Luca Santoro, Giovanni Pecorini, Flavia Angelini, and Giovanni Ghirlanda
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Male ,Genetic profile ,medicine.medical_specialty ,TNFRSF11B gene polymorphisms ,Biology ,Polymorphism, Single Nucleotide ,Gastroenterology ,Diabetes Complications ,Osteoprotegerin ,Risk Factors ,Internal medicine ,Diabetes mellitus ,Genotype ,Genetics ,medicine ,Humans ,Stroke ,Genetic Association Studies ,Genetics (clinical) ,Aged ,Retrospective Studies ,Base Sequence ,Diabetes ,Settore MED/09 - MEDICINA INTERNA ,Case-control study ,Retrospective cohort study ,DNA ,medicine.disease ,Molecular medicine ,Italy ,History of ischemic stroke ,Case-Control Studies ,Female ,Restriction fragment length polymorphism - Abstract
Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family and plays a role in atherosclerosis. The present study aimed to evaluate whether OPG gene (TNFRSF11B) polymorphisms are involved in ischemic stroke in an Italian population with diabetes. Participants in a retrospective case–control study included 364 diabetic patients (180 males, 184 females) with history of ischemic stroke and 492 diabetic subjects without history of ischemic stroke (252 males, 240 females). The T245G, T950C, and G1181C polymorphisms of the OPG gene were analyzed by polymerase chain reaction and restriction fragment length polymorphism. We found that the T245G, T950C, and G1181C gene polymorphisms of the OPG gene were significantly (34.1 vs. 9.5 %, P more...
- Published
- 2012
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8. Ex vivo-transduced autologous skin fibroblasts expressing human Lim mineralization protein-3 efficiently form new bone in animal models
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Giovanni Pecorini, Raffaella Pecci, Anna Tampieri, Rossella Bedini, Egidio Stigliano, Paul D. Robbins, Enrico Pola, Claudio Parrilla, Annarita Fetoni, Wanda Lattanzi, Giandomenico Logroscino, Giuseppe Straface, Andrea Gambotto, Fabrizio Michetti, Lattanzi, W, Parrilla, C, Fetoni, A, Logroscino, G, Straface, G, Pecorini, G, Stigliano, E, Tampieri, A, Bedini, R, Pecci, R, Michetti, F, Gambotto, A, Robbins, Pd, and Pola, E more...
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Male ,Pathology ,Genetic enhancement ,Gene Expression ,Mice ,Osteogenesis ,Transduction, Genetic ,Tissue Scaffolds ,Reverse Transcriptase Polymerase Chain Reaction ,Intracellular Signaling Peptides and Proteins ,Osteoblast ,LIM Domain Proteins ,Lim mineralization protein-3 ,animal models ,Cell biology ,medicine.anatomical_structure ,Models, Animal ,Bone formation ,Molecular Medicine ,Bone Diseases ,Autologous transplantation ,medicine.medical_specialty ,Genetic Vectors ,Skin fibroblasts ,Bone healing ,Biology ,Transplantation, Autologous ,Bone and Bones ,Article ,Adenoviridae ,In vivo ,Genetics ,medicine ,Animals ,Humans ,Rats, Wistar ,Fibroblast ,Molecular Biology ,Adaptor Proteins, Signal Transducing ,Settore BIO/16 - ANATOMIA UMANA ,LMP ,Genetic Therapy ,Fibroblasts ,Rats ,Mice, Inbred C57BL ,Transplantation ,Cytoskeletal Proteins ,Tomography, X-Ray Computed ,Ex vivo - Abstract
Local gene transfer of the human LIM Mineralization Protein (LMP), a novel intracellular positive regulator of the osteoblast differentiation program, can induce efficient bone formation in rodents. In order to develop a clinically relevant gene therapy approach to facilitate bone healing, we have used primary dermal fibroblasts transduced ex vivo with Ad.LMP3 and seeded on an hydroxyapatite/collagen matrix prior to autologous implantation. Here we demonstrate that genetically modified autologous dermal fibroblasts expressing Ad.LMP-3 are able to induce ectopic bone formation following implantation of the matrix into the mouse triceps and paravertebral muscles. Moreover, implantation of the Ad.LMP-3-modified dermal fibroblasts into a rat mandibular bone critical size defect model results in efficient healing as determined by X-ray, histology and three dimensional micro computed tomography (3DμCT). These results demonstrate the effectiveness of the non-secreted intracellular osteogenic factor LMP-3, in inducing bone formation in vivo. Moreover, the utilization of autologous dermal fibroblasts implanted on a biomaterial represents a promising approach for possible future clinical applications aimed at inducing new bone formation. more...
- Published
- 2008
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9. Peroxisome Proliferator-Activated Receptor Alpha Is Crucial for Iloprost-Induced in vivo Angiogenesis and Vascular Endothelial Growth Factor Upregulation
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Federico Biscetti, Eleonora Gaetani, Roy C. Smith, John J. Castellot, Flavia Angelini, Roberto Pola, Giuseppe Straface, Giovanni Pecorini, Egidio Stigliano, Andrea Flex, and Tamar Aprahamian
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Vascular Endothelial Growth Factor A ,Physiology ,Angiogenesis ,Transfection ,Vascular endothelial growth inhibitor ,Mice ,chemistry.chemical_compound ,medicine ,Animals ,Corneal Neovascularization ,PPAR alpha ,Iloprost ,RNA, Messenger ,Mice, Knockout ,Vascular Endothelial Growth Factor Receptor-1 ,Chemistry ,Up-Regulation ,Vascular endothelial growth factor B ,Vascular endothelial growth factor ,Vascular endothelial growth factor A ,Vascular endothelial growth factor C ,cardiovascular system ,Cancer research ,Angiogenesis Inducing Agents ,lipids (amino acids, peptides, and proteins) ,Peroxisome proliferator-activated receptor alpha ,Cardiology and Cardiovascular Medicine ,Signal Transduction ,circulatory and respiratory physiology ,medicine.drug - Abstract
We have previously demonstrated that iloprost, a stable prostacyclin (PGI2) analogue, induces angiogenesis in vivo, through a vascular endothelial growth factor (VEGF)-dependent mechanism. In this study, we demonstrate that iloprost-induced angiogenesis and VEGF upregulation are modulated by peroxisome proliferator-activated receptor-α (PPARα), a ligand-inducible transcription factor that belongs to the nuclear hormone receptor superfamily and plays multiple biological activities in the vascular system. We show that iloprost is unable to induce angiogenesis in mice lacking the PPARα gene (PPARα–/– mice). Likewise, iloprost-induced VEGF upregulation is absent in PPARα–/– mice. In contrast, iloprost induces a robust angiogenic response in wild-type mice, along with local upregulation of VEGF. Importantly, mice lacking the PPARα gene exhibit a normal angiogenic response to VEGF, indicating that the absence of PPARα does not result in a general impairment of angiogenesis, but specifically affects the ability of iloprost to induce angiogenesis. Our data demonstrate unexpected functional relationships between the PGI2 system and the PPAR signaling pathway and shed new light on the molecular mechanisms involved in iloprost-induced angiogenesis. more...
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- 2008
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10. The role of high‐mobility group box protein 1 in collagen antibody‐induced arthritis is dependent on vascular endothelial growth factor
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Federico Biscetti, Gianfranco Ferraccioli, Elisa Gremese, Flavia Angelini, Egidio Stigliano, Barbara Tolusso, Andrea Flex, Giovanni Pecorini, and Vincenzo Arena
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0301 basic medicine ,Male ,Vascular Endothelial Growth Factor A ,Settore MED/16 - REUMATOLOGIA ,Angiogenesis ,Interleukin-1beta ,Arthritis ,Gene Expression ,Severity of Illness Index ,chemistry.chemical_compound ,Mice ,Immunology and Allergy ,Medicine ,HMGB1 Protein ,Vascular endothelial growth factor ,Mice, Inbred BALB C ,biology ,Neovascularization, Pathologic ,Anti-Inflammatory Agents, Non-Steroidal ,Interleukin-17 ,Synovial Membrane ,Vascular endothelial growth factor A ,medicine.anatomical_structure ,Interleukin 17 ,Immunology ,chemical and pharmacologic phenomena ,Antibodies ,03 medical and health sciences ,High-mobility group box 1 ,Synovial fluid ,Animals ,Rheumatoid arthritis ,Interleukin 6 ,Collagen Type II ,Vascular Endothelial Growth Factor Receptor-1 ,business.industry ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Settore MED/09 - MEDICINA INTERNA ,Original Articles ,medicine.disease ,Arthritis, Experimental ,030104 developmental biology ,chemistry ,biology.protein ,Synovial membrane ,business ,Peptides - Abstract
Summary High-mobility group box 1 (HMGB1) has been implicated in angiogenesis and rheumatoid arthritis (RA). The aim of this study was to define more clearly the role of HMGB1 in the synovial angiogenesis and pathogenesis of an immune model of arthritis. BALB/c mice were injected with monoclonal anti-collagen antibody cocktail followed by lipopolysaccharide to induce arthritis. HMGB1 and vascular endothelial growth factor (VEGF) were over-expressed in the areas of the synovium where more inflammation and neoangiogenesis were present. The selective blockade of HMGB1 or VEGF resulted alternatively in a lower severity of arthritis evaluated by the arthritis index. Furthermore, exogenous HMGB1 administration caused a worsening of arthritis, associated with VEGF up-regulation and increased synovial angiogenesis. The selective inhibition of VEGF also resulted in no induction of arthritis in mice receiving exogenous HMGB1. Cytokine enzyme-linked immunosorbent assay (ELISA) analyses performed on peripheral blood and synovial fluid demonstrated a significant reduction of interleukin (IL)−1β, IL-6 and tumour necrosis factor (TNF)-α in mice where HMGB1 and VEGF pathways were blocked. Interestingly, the selective blockade of HMGB1 and VEGF resulted in an increase of the peripheral IL-17A concentration. The development of arthritis mediated by HMGB1 and the synovial angiogenesis can be blocked by inhibiting the VEGF activity. The proinflammatory and proangiogenic cytokine IL-17A was increased when HMGB1 is inhibited, but the synovial angiogenesis was nevertheless reduced in this model of arthritis. Taken together, these findings shed new light on the role of this nuclear protein in the pathogenesis of arthritis in an RA-like model. more...
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- 2016
11. Increased FGF23 serum level is associated with unstable carotid plaque in type 2 diabetic subjects with internal carotid stenosis
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Flavia Angelini, Antonio Bianchi, Raffaele Landolfi, Claudio Vincenzoni, Francesco Snider, Andrea Flex, Giovanni Pecorini, Giuseppe Straface, Carlo Filippo Porreca, Giovanni Bertoletti, Vincenzo Arena, Egidio Stigliano, and Federico Biscetti more...
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Male ,medicine.medical_specialty ,Internal carotid artery stenosis ,Endocrinology, Diabetes and Metabolism ,Carotid arteries ,medicine.medical_treatment ,education ,Unstable Plaque ,Type 2 diabetes ,FGF23 ,Internal medicine ,Diabetes mellitus ,Humans ,Medicine ,Carotid Stenosis ,Aged ,Retrospective Studies ,Original Investigation ,Endarterectomy ,Angiology ,Endarterectomy, Carotid ,business.industry ,Settore MED/09 - MEDICINA INTERNA ,Ultrasonography, Doppler ,medicine.disease ,Plaque, Atherosclerotic ,Fibroblast Growth Factors ,Fibroblast Growth Factor-23 ,stomatognathic diseases ,Stenosis ,Diabetes Mellitus, Type 2 ,Cardiology ,Female ,OPG ,Ultrasonography ,Cardiology and Cardiovascular Medicine ,business ,Carotid Artery, Internal - Abstract
Background The object of this study was to investigate the potential role of FGF23 on plaque stability in type 2 diabetic patients with internal carotid artery stenosis. Methods In this retrospective observational study, we analyzed FGF23 serum level in 361 type 2 diabetic patients with internal carotid artery stenosis undergoing carotid endarterectomy and in 598 diabetic controls without carotid atherosclerosis. Results We found that FGF23 median serum levels was significantly higher in patients than in diabetic controls [67.7 (59.5–77.8) pg/mL and 43.89 (37.5–50.4), P more...
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- 2015
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12. Analysis of Functional Polymorphisms of Metalloproteinase Genes in Persons With Vascular Dementia and Alzheimer's Disease
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Alexandra Sabusco, Andrea Flex, Giovanni Pecorini, Eleonora Gaetani, Roberto Pola, Anna S. Proia, Roberto Flore, Giuseppe Fioroni, Paolo Tondi, Giuseppe Straface, Paolo Pola, and Federico Biscetti
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Male ,Apolipoprotein E ,Oncology ,Aging ,medicine.medical_specialty ,Genotype ,Disease ,Apolipoproteins E ,Alzheimer Disease ,Internal medicine ,medicine ,Humans ,Dementia ,Allele ,Vascular dementia ,Aged ,Aged, 80 and over ,Polymorphism, Genetic ,business.industry ,Dementia, Vascular ,Odds ratio ,medicine.disease ,Matrix Metalloproteinases ,Cross-Sectional Studies ,Genetic marker ,Immunology ,Female ,Geriatrics and Gerontology ,business - Abstract
Background. Vascular dementia (VAD) and Alzheimer’s disease (AD) may share common neuropathological mechanisms. Matrix metalloproteinases (MMPs) may induce destruction of the extracellular matrix, neuronal dysfunction, and death. Increased expression of these molecules has been found in a number of neurological diseases, including cerebral ischemia and AD. Expression and activity of MMPs may be genetically influenced by common polymorphisms in the promoter regions of the corresponding genes. The purpose of this study was to evaluate whether functional polymorphisms of MMP genes are associated with dementia. Methods. This is a cross-sectional study including a total of 599 individuals: 193 with VAD, 183 with AD, and 223 controls. Polymorphisms of the MMP-1, MMP-3, and MMP-9 genes were studied. Results. MMP-1 2G2G, MMP-1 1G2G, MMP-3 5A5A, and MMP-9 TT genotypes were significantly and independently associated with VAD (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.4–4.4, OR ¼ 1.7, 95% CI, 1.0–2.7, OR ¼ 2.9, 95% CI, 1.5–5.9, and OR ¼ 6.8, 95% CI, 1.3–35.1, respectively). MMP-1 2G2G and MMP-3 5A5A genotypes were associated with increased risk of AD only in persons who carry the apolipoprotein E (APOE) e4 allele (OR ¼ 6.0, 95% CI, 2.3–15.5, and OR ¼ 14.3, 95% CI, 3.2–63.0, respectively). Interestingly, the odds of VAD and AD was further increased in persons concomitantly carrying more than one MMP gene variation, compared to individuals that only had one high-risk genotype. Conclusions. Our study suggests that MMP gene polymorphisms are associated with VAD and AD, although these results need to be treated with caution until replicated. MMP genotypes may influence the risk of dementia and merit further investigation as potential genetic markers of disease. more...
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- 2006
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13. Cilostazol improves the response to ischemia in diabetic mice by a mechanism dependent on PPARγ
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Federico Biscetti, Andrea Flex, Vincenzo Arena, Giovanni Ghirlanda, Flavia Angelini, Gianfranco Ferraccioli, Giovanni Pecorini, and Egidio Stigliano
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Male ,Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,PPARγ ,Angiogenesis ,Ischemia ,Peroxisome proliferator-activated receptor ,Neovascularization, Physiologic ,Tetrazoles ,Biochemistry ,Diabetes Mellitus, Experimental ,Mice ,Endocrinology ,Internal medicine ,Diabetes mellitus ,medicine ,Animals ,Receptor ,Molecular Biology ,chemistry.chemical_classification ,business.industry ,Diabetes ,Settore MED/09 - MEDICINA INTERNA ,medicine.disease ,Streptozotocin ,Cilostazol ,Hindlimb ,Mice, Inbred C57BL ,PPAR gamma ,chemistry ,Regional Blood Flow ,Angiogenesis Inducing Agents ,business ,Perfusion ,medicine.drug - Abstract
Cilostazol is effective for the treatment of peripheral ischemia. This compound has several beneficial effects on platelet aggregation, serum lipids and endothelial cells, and we recently found that it enhances collateral blood flow in the ischemic hind limbs of mice. Peroxisome proliferator-activated receptor (PPAR)γ, a receptor for thiazolidinediones, plays a role in angiogenesis. The aim of this work was to investigate the underlying molecular mechanisms and effects of cilostazol in a model of peripheral ischemia in diabetic mice. We induced diabetes in mice by streptozotocin (STZ) administration and studied ischemia-induced angiogenesis in the ischemic hind limbs of cilostazol-treated and untreated control mice. We found that perfusion recovery was significantly improved in treated compared with control diabetic mice. Interestingly, we found that the expression of PPARγ is reduced in ischemic tissues of diabetic mice. Furthermore, we discovered that local inhibition of the activity of this nuclear receptor decreased the angiogenic response to cilostazol treatment. Finally, we noted that this phenomenon is dependent on VEGF and modulated by PPARγ. Cilostazol administration enhances collateral blood flow in the ischemic hind limbs of STZ-induced diabetic mice through a PPARγ-dependent mechanism. more...
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- 2013
14. Cilostazol promotes angiogenesis after peripheral ischemia through a VEGF-dependent mechanism
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Federico Biscetti, Andrea Flex, Giovanni Ghirlanda, Giovanni Pecorini, Egidio Stigliano, Flavia Angelini, Franco Locatelli, Giuseppe Straface, Vincenzo Arena, and Sergio Rutella
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Male ,Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,Angiogenesis ,Vasodilator Agents ,Neovascularization, Physiologic ,Tetrazoles ,Hindlimb ,Neovascularization ,chemistry.chemical_compound ,Mice ,Downregulation and upregulation ,Ischemia ,Internal medicine ,medicine ,Animals ,Progenitor cell ,peripheral ischemia ,business.industry ,Settore MED/09 - MEDICINA INTERNA ,Cilostazol ,Vascular endothelial growth factor ,VEGF ,Intermittent claudication ,Up-Regulation ,Mice, Inbred C57BL ,Disease Models, Animal ,Endocrinology ,chemistry ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Background/objectives Cilostazol has been found to be effective for the treatment of intermittent claudication (IC). This compound has several beneficial effects on platelet aggregation, serum lipids and endothelial cells, but how these might relate to improvements in walking is not entirely understood. The aim of this work was to investigate the effects of cilostazol on angiogenic response in a murine model of peripheral ischemia and to clarify the underlying molecular mechanisms of that response. Methods We studied ischemia-induced neovascularization in the ischemic hindlimb of cilostazol-treated and untreated control mice. Results We found that the perfusion recovery was significantly improved in treated compared with control mice. Interestingly, there was a higher level of circulating endothelial progenitor cells (EPCs) in mice treated with cilostazol than in untreated mice. Furthermore, cilostazol administration resulted in upregulation of granulocyte colony-stimulating factor (G-CSF) and vascular endothelial growth factor (VEGF) in the ischemic muscle of treated mice. Finally, inhibiting VEGF activity significantly reduced cilostazol-induced angiogenesis. Conclusions The results of this study show that cilostazol administration enhances collateral blood flow in the ischemic hindlimbs of mice through a VEGF-dependent mechanism. These data may help to explain the beneficial effects that this drug has on patients with peripheral arterial disease (PAD) and IC. more...
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- 2012
15. Sonic Hedgehog Regulates Angiogenesis and Myogenesis During Post-Natal Skeletal Muscle Regeneration
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Egidio Stigliano, John J. Castellot, Douglas W. Losordo, Federico Biscetti, Giovanni Pecorini, Roy C. Smith, Flavia Angelini, Eleonora Gaetani, Giuseppe Straface, Roberto Pola, Andrea Flex, Enrico Pola, Tamar Aprahamian, Straface, G, Aprahamian, T, Flex, A, Gaetani, E, Biscetti, F, Smith, Rc, Pecorini, G, Pola, E, Angelini, F, Stigliano, E, Castellot, Jj, Losordo, Dw, and Pola, R more...
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medicine.medical_specialty ,animal structures ,Angiogenesis ,Neovascularization, Physiologic ,Tissue Regeneration ,MyoD ,Mice ,chemistry.chemical_compound ,sonic hedgehog ,angiogenesis ,Internal medicine ,skeletal muscle regeneration ,medicine ,Animals ,Hedgehog Proteins ,Sonic hedgehog ,skeletal muscle ,Muscle, Skeletal ,biology ,Myogenesis ,Settore MED/09 - MEDICINA INTERNA ,Skeletal muscle ,angiogenesi ,Cell Biology ,Hedgehog signaling pathway ,Cell biology ,Mice, Inbred C57BL ,Vascular endothelial growth factor ,Endocrinology ,medicine.anatomical_structure ,chemistry ,regeneration ,Myogenic regulatory factors ,embryonic structures ,biology.protein ,Molecular Medicine ,myogenesis - Abstract
Sonic hedgehog (Shh) is a morphogen regulating crucial epithelial-mesenchymal interactions during embryonic development, but its signaling pathway is considered generally silent in post-natal life. In this study, we demonstrate that Shh is de novo expressed after injury and during regeneration of the adult skeletal muscle. Shh expression is followed by significant upregulation of its receptor and target gene Ptc1 in injured and regenerating muscles. The reactivation of the Shh signaling pathway has an important regulatory role on injury-induced angiogenesis, as inhibition of Shh function results in impaired upregulation of prototypical angiogenic agents, such as vascular endothelial growth factor (VEGF) and stromal-derived factor (SDF)-1alpha, decreased muscle blood flow, and reduced capillary density after injury. In addition, Shh reactivation plays a regulatory role on myogenesis, as its inhibition impairs the activation of the myogenic regulatory factors Myf-5 and MyoD, decreases the upregulation of insulin-like growth factor (IGF)-1, and reduces the number of myogenic satellite cells at injured site. Finally, Shh inhibition results in muscle fibrosis, increased inflammatory reaction, and compromised motor functional recovery after injury. These data demonstrate that the Shh pathway is functionally important for adult skeletal muscle regeneration and displays pleiotropic angiogenic and myogenic potentials in post-natal life. These findings might constitute the foundation for new therapeutic approaches for muscular diseases in humans. Sonic hedgehog (Shh) is a morphogen-regulating crucial epithelial-mesenchymal interactions during embryonic development, but its signalling pathway is considered generally silent in post-natal life. In this study, we demonstrate that Shh is de novo expressed after injury and during regeneration of the adult skeletal muscle. Shh expression is followed by significant up-regulation of its receptor and target gene Ptc1 in injured and regenerating muscles. The reactivation of the Shh signalling pathway has an important regulatory role on injury-induced angiogenesis, as inhibition of Shh function results in impaired up-regulation of prototypical angiogenic agents, such as vascular endothelial growth factor (VEGF) and stromal-derived factor (SDF)-1alpha, decreased muscle blood flow and reduced capillary density after injury. In addition, Shh reactivation plays a regulatory role on myogenesis, as its inhibition impairs the activation of the myogenic regulatory factors Myf-5 and MyoD, decreases the up-regulation of insulin-like growth factor (IGF)-1 and reduces the number of myogenic satellite cells at injured site. Finally, Shh inhibition results in muscle fibrosis, increased inflammatory reaction and compromised motor functional recovery after injury. These data demonstrate that the Shh pathway is functionally important for adult skeletal muscle regeneration and displays pleiotropic angiogenic and myogenic potentials in post-natal life. These findings might constitute the foundation for new therapeutic approaches for muscular diseases in humans. more...
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- 2009
16. Growth hormone receptor polymorphism and the effects of pegvisomant in acromegaly
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Vincenzo Cimino, Gherardo Mazziotti, Flora Veltri, Giovanni Pecorini, Antonio Bianchi, L. Tilaro, Laura De Marinis, Alfredo Pontecorvi, Andrea Giustina, Eleonora Gaetani, Bianchi, A, Mazziotti, G, Tilaro, L, Cimino, V, Veltri, F, Gaetani, E, Pecorini, G, Pontecorvi, A, Giustina, Andrea, and De Marinis, L. more...
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Somatostatin Analog Therapy ,Growth hormone receptor ,Polymerase Chain Reaction ,Young Adult ,Endocrinology ,Internal medicine ,Genotype ,Acromegaly ,Humans ,Medicine ,Insulin-Like Growth Factor I ,Receptor ,Aged ,Polymorphism, Genetic ,Human Growth Hormone ,business.industry ,Settore MED/13 - ENDOCRINOLOGIA ,Exons ,Receptors, Somatotropin ,Middle Aged ,medicine.disease ,Regimen ,Haplotypes ,Pegvisomant ,Female ,Neurosurgery ,business ,medicine.drug - Abstract
Background Sensitivity to pegvisomant therapy is highly variable in patients with acromegaly but determinants of this variability are still unknown. Lack of exon 3 (d3-) of the growth hormone (GH) receptor (GHR) has been associated with increased biological activity of GH. Objective To assess whether the presence of d3-GHR haplotype may have a role in predicting dose regimen and response to pegvisomant in acromegaly. Design Case series. Setting Institutional referral center at a tertiary care hospital. Patients Ninenteen acromegalic patients with active disease after unsuccessful neurosurgery and somatostatin analog therapy. Measurements before and 1, 3, 6 and 12 months after treatment with pegvisomant, IGF-I; GH receptor genotype, determined from peripheral blood by polymerase chain reaction. All patients started treatment with pegvisomant at 10 mg/daily and then increased the dose, according to a fixed schedule, during a 12-month follow-up until normalization of IGF-I levels. Results d3-GHR patients required a significant lower dose of pegvisomant and shorter treatment time to normalize IGF-I. Conclusion the GHR genotype could be useful in predicting dose and individual response to pegvisomant in acromegaly. more...
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- 2009
17. Selective activation of peroxisome proliferator-activated receptor (PPAR)alpha and PPAR gamma induces neoangiogenesis through a vascular endothelial growth factor-dependent mechanism
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Roberto Pola, John J. Castellot, Teresa Hopkins, Giovanni Pecorini, Egidio Stigliano, Eleonora Gaetani, Tamar Aprahamian, Flavia Angelini, Federico Biscetti, Roy C. Smith, Andrea Flex, and Giuseppe Straface more...
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Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,Umbilical Veins ,Endothelium ,PPARs ,Angiogenesis ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Peroxisome proliferator-activated receptor ,Neovascularization, Physiologic ,Suramin ,Biology ,Neovascularization ,chemistry.chemical_compound ,angiogenesis ,Cell Movement ,Internal medicine ,Internal Medicine ,medicine ,Humans ,PPAR alpha ,Protein kinase B ,Tube formation ,chemistry.chemical_classification ,Settore MED/09 - MEDICINA INTERNA ,Coculture Techniques ,Vascular endothelial growth factor ,PPAR gamma ,medicine.anatomical_structure ,Endocrinology ,Cytokine ,chemistry ,Cancer research ,Endothelium, Vascular ,medicine.symptom ,Cell Division - Abstract
OBJECTIVE—Peroxisome proliferator–activated receptors (PPARs) are therapeutic targets for fibrates and thiazolidinediones, which are commonly used to ameliorate hyperlipidemia and hyperglycemia in type 2 diabetes. In this study, we evaluated whether activation of PPARα and PPARγ stimulates neoangiogenesis. RESEARCH DESIGN AND METHODS—We used selective synthetic PPARα and PPARγ agonists and investigated their angiogenic potentials in vitro and in vivo. RESULTS—Activation of PPARα and PPARγ leads to endothelial tube formation in an endothelial/interstitial cell co-culture assay. This effect is associated with increased production of the angiogenic cytokine vascular endothelial growth factor (VEGF). Neovascularization also occurs in vivo, when PPARα and PPARγ agonists are used in the murine corneal angiogenic model. No vascular growth is detectable when PPARα and PPARγ agonists are respectively used in PPARα knockout mice and mice treated with a specific PPARγ inhibitor, demonstrating that this angiogenic response is PPAR mediated. PPARα- and PPARγ-induced angiogenesis is associated with local VEGF production and does not differ in extent and morphology from that induced by VEGF. In addition, PPARα- and PPARγ-induced in vitro and in vivo angiogenesis may be significantly decreased by inhibiting VEGF activity. Finally, in corneas treated with PPARα and PPARγ agonists, there is increased phosphorylation of endothelial nitric oxide synthase and Akt. CONCLUSIONS—These findings demonstrate that PPARα and PPARγ activation stimulates neoangiogenesis through a VEGF-dependent mechanism. Neoangiogenesis is a crucial pathological event in type 2 diabetes. The ability of PPARα and PPARγ agonists to induce neoangiogenesis might have important implications for the clinical and therapeutic management of type 2 diabetes. more...
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- 2008
18. Evaluation of the anti-tuberculosis activity generated by different multigene DNA vaccine constructs
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Antonella Zumbo, Giovanni Delogu, Stefania Anna Lucia Zanetti, Michela Sali, Sandra Clarizio, Cinzia Pusceddu, Giovanni Fadda, Giovanni Pecorini, and Stefano Rocca
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Recombinant Fusion Proteins ,Immunology ,chemical and pharmacologic phenomena ,Immunofluorescence ,Inbred C57BL ,Microbiology ,Epitope ,Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA ,DNA vaccination ,Mycobacterium tuberculosis ,Mice ,Antigen ,medicine ,Tumor Cells, Cultured ,Vaccines, DNA ,Animals ,Tuberculosis ,Antigens ,Tuberculosis Vaccines ,Antigens, Bacterial ,Vaccines, Synthetic ,Vaccines ,Cultured ,biology ,medicine.diagnostic_test ,Synthetic ,Bacterial ,DNA ,biology.organism_classification ,Fusion protein ,Virology ,Tumor Cells ,Mice, Inbred C57BL ,Infectious Diseases ,biology.protein ,Antibody ,Tuberculosis vaccines - Abstract
Development of multigenic constructs expressing Mycobacterium tuberculosis (Mtb) antigens may be a strategy to obtain improved DNA vaccines against tuberculosis (TB). Several multigenic constructs expressing two or three Mtb antigens as fusion proteins were developed, both as tPA- and ubiquitin-fusion proteins. To demonstrate proper protein expression and intracellular turnover all multiantigens were tagged with the HA epitope and constructs were used to transfect rhabdomyosarcoma (RD) cells. Antigen expression was demonstrated by immunofluorescence using anti-HA antibodies. C57Bl/6 mice were immunized with selected constructs and protective activity was assessed following aerogenic challenge with Mtb. Several of these constructs induced a significant level of protection in the lung and in the spleen. Immunization with the construct expressing tPA85B-ES6 induced a level of protection that approached that provided by BCG. Immunization with a combination of these constructs induced levels of protection that were not superior to those elicited by a single combination, and immunization with a construct expressing five Mtb antigens could not provide an improved level of protection compared to tPA85B-ES6. We conclude that the activity of a DNA vaccine based on tPA85B-ES6 cannot be enhanced by broadening the antigen repertoire with other highly immunogenic secreted Mtb proteins. more...
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- 2008
19. [Editorial comment. Stress echocardiography in valvular heart disease]
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Marco, Pascotto, Giovanni, Pecorini, Angelo, Russo, and Federico, Gentile
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Heart Valve Diseases ,Humans ,Echocardiography, Stress - Published
- 2007
20. Abstract 2178: Sonic Hedgehog In Adult Hypoxic Cerebellum
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Giuseppe Straface, Andrea Flex, Federico Biscetti, Eleonora Gaetani, Giovanni Pecorini, Flavia Angelini, Paolo Pola, and Roberto Pola
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Physiology (medical) ,Cardiology and Cardiovascular Medicine - Abstract
Background: Cerebellar hypoxia is responsible for important aspects of cognitive deterioration and motor disturbances in neurological disorders, such as stroke, vascular dementia, and neurodegeneration. In the cerebellum, VEGF is significantly upregulated after hypoxia and is able to induce angiogenesis, reduce neuronal apoptosis, and regulate neuronal differentiation, proliferation, and migration. But, VEGF is not sufficient to provide neuroprotection. A crucial role is played by growth associated protein-43 (GAP43), for which important activities have been described. The purpose of this study was to investigate the role of the developmental Sonic hedgehog (Shh) signaling pathway in postnatal hypoxic cerebellum and its relationship with VEGF and GAP43 expression. Methods: We used adult C57BL/6J mice, ptc1-lacZ mice, and GAP43−/− mice for these experiments. Ptc1-lacZ mice carry a non-disruptive insertion of the lacZ gene under the control of the ptc1 promoter. Ptc1 is a downstream-transcriptional target of Shh and its upregulation indicates activation of the Shh pathway. Mice were exposed to systemic normobaric hypoxia (6%O 2 ) for 6 hours and the expression of Shh, Ptc1, VEGF, and GAP43 were investigated. Results: After exposure to hypoxia, Shh-positive staining was detected in Purkinje cells (PCs). The same cells were also lacZ(ptc1)-positive, indicating that PCs are both Shh-producing and -responding elements. Also the cells of the internal granular layer (IGL) were lacZ(ptc1)-positive, indicating that these cells are Shh-responsive. LacZ(ptc1)-positive IGL cells were also immunopositive for VEGF and GAP-43. We also found that ptc1 expression is lost in PCs of GAP43−/− mice, indicating that Shh requires GAP43 to activate its downstream target genes in PCs. Finally, when cultures enriched in granular cells were stimulated with Shh recombinant protein, GAP43 phosphorylation was increased. This effect was inhibited by Shh-inhibitor cyclopamine. Conclusions: This is the first time that hypoxia is reported to activate the Shh pathway in the adult. Our data suggest that the Shh pathway might be important for the cerebellar response to hypoxia, through interactions with VEGF and GAP43. more...
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- 2007
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21. Evaluation of VITEK 2 and RapID yeast plus systems for yeast species identification: experience at a large clinical microbiology laboratory
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Brunella Posteraro, Michela Sali, Maurizio Sanguinetti, Giovanni Fadda, Marilena La Sorda, Giovanni Pecorini, and Rosaria Porta
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Microbiology (medical) ,Genetics ,Sequence analysis ,Mycology ,Sequence Analysis, DNA ,Ribosomal RNA ,Biology ,bacterial infections and mycoses ,equipment and supplies ,Yeast ,Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA ,Microbiology ,Clinical microbiology ,fluids and secretions ,Mycoses ,Yease identification ,Yeasts ,DNA, Ribosomal Spacer ,Species identification ,Humans ,Internal transcribed spacer ,DNA, Fungal - Abstract
A total of 750 clinical yeast isolates were evaluated by two identification systems, VITEK 2 and RapID Yeast Plus, using sequence analysis of the rRNA gene internal transcribed spacer regions as the reference method. The VITEK 2 and RapID systems correctly identified 737 (98.2%) and 716 (95.5%) isolates, respectively. more...
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- 2007
22. Use of microelectronic array technology for rapid identification of clinically relevant mycobacteria
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Brunella Posteraro, Giovanni Fadda, Elena De Carolis, Stefania Ranno, Fausta Ardito, Linda Novarese, Barbara Lucignano, Maurizio Sanguinetti, and Giovanni Pecorini
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Microbiology (medical) ,Identification methods ,Time Factors ,Computational biology ,Biology ,Polymerase Chain Reaction ,Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA ,Microbiology ,Mycobacterium ,Lab-On-A-Chip Devices ,RNA, Ribosomal, 16S ,Microchip Analytical Procedures ,Microelectronics ,Humans ,Nanotechnology ,Tuberculosis ,Mycobacteria growth indicator tube ,RNA RIBOSOMAL 16S ,Oligonucleotide Array Sequence Analysis ,Mycobacterium Infections ,business.industry ,Mycobacteriology and Aerobic Actinomycetes ,Mycobacterium tuberculosis ,Bacterial Typing Techniques ,Rapid identification ,Identification (biology) ,business ,Oligonucleotide Probes - Abstract
We developed a new method based on the Nanochip microelectronic array technology for identification of various clinically relevant mycobacterial species. PCR-amplified rRNA genes obtained from 270 positive Mycobacteria Growth Indicator Tube cultures were successfully tested by hybridizing them with species-selective probes, and the results agreed with those of conventional identification methods. The system is rapid and accurate and opens new perspectives in clinical diagnostics. more...
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- 2005
23. Monocyte chemoattractant protein-1 (MCP-1) gene polymorphism and risk of Alzheimer's disease in Italians
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Pierangelo Papaleo, Andrea Flex, Angela Di Giorgio, Paolo Pola, Roberto Pola, Giovanni Pecorini, Eleonora Gaetani, Anna S. Proia, Michele Serricchio, and Giuseppe Straface
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Male ,Aging ,Monocyte chemotaxis ,gene polymorphism ,Genotype ,alzheimer ,Population ,Single-nucleotide polymorphism ,Biology ,Biochemistry ,Pathogenesis ,Endocrinology ,Apolipoproteins E ,Alzheimer Disease ,Genetics ,Humans ,Genetic Predisposition to Disease ,Allele ,education ,Molecular Biology ,Gene ,Chemokine CCL2 ,Aged ,Aged, 80 and over ,education.field_of_study ,Polymorphism, Genetic ,Interleukin-6 ,Settore MED/09 - MEDICINA INTERNA ,Homozygote ,Cell Biology ,Intercellular Adhesion Molecule-1 ,Logistic Models ,Italy ,inflammation ,Case-Control Studies ,Immunology ,Female ,Gene polymorphism ,MCP-1 - Abstract
Monocyte chemoattractant protein-1 (MCP-1) is a key molecule for monocyte chemotaxis and tissue extravasation and for the modulation of leukocyte function during inflammation. Upregulation of MCP-1 may occur in the brain of subjects affected by Alzheimer's disease (AD) and MCP-1 levels in plasma and cerebrospinal fluid have been proposed as biological markers for the inflammatory process that accompanies AD pathogenesis. Importantly, serum levels and biological activity of MCP-1 protein are strongly influenced by a single nucleotide polymorphism occurring at position −2518 of the MCP-1 gene promoter. A recent study has investigated the possible association between this gene polymorphism and AD in a Spanish population, with negative results. Here, we performed a case–control study to test whether the risk for AD might be influenced by the −2518 A/G polymorphism of the MCP-1 gene in an ethnically homogeneous Italian population. The GG genotype and the G allele of the MCP-1 gene polymorphism were significantly more common in the AD group than in control individuals (P more...
- Published
- 2004
24. Proinflammatory genetic profiles in subjects with history of ischemic stroke
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Eleonora Gaetani, Roberto Pola, Giovanni Pecorini, Andrea Flex, Pierangelo Papaleo, Anna S. Proia, Giuseppe Straface, Paolo Tondi, and Paolo Pola
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Male ,Genotype ,gene polymorphism ,genetic profiles ,Ischemia ,Single-nucleotide polymorphism ,Inflammation ,Proinflammatory cytokine ,Risk Factors ,medicine ,Humans ,Immunologic Factors ,Stroke ,Macrophage Migration-Inhibitory Factors ,Chemokine CCL2 ,Aged ,Advanced and Specialized Nursing ,Polymorphism, Genetic ,business.industry ,Interleukin-6 ,Monocyte ,Settore MED/09 - MEDICINA INTERNA ,Middle Aged ,medicine.disease ,Intercellular Adhesion Molecule-1 ,stroke ,medicine.anatomical_structure ,C-Reactive Protein ,inflammation ,Case-Control Studies ,Immunology ,Macrophage migration inhibitory factor ,Female ,Matrix Metalloproteinase 3 ,Neurology (clinical) ,medicine.symptom ,Inflammation Mediators ,Cardiology and Cardiovascular Medicine ,business ,E-Selectin ,Biomarkers - Abstract
Background and Purpose— Proinflammatory genetic profiles, resulting from the combination of single nucleotide polymorphisms in genes encoding inflammatory molecules, may contribute to the development and progression of cardiovascular diseases. We evaluated the association between history of ischemic stroke and genetic profiles determined by the synergistic effects of polymorphisms in genes encoding prototypical inflammatory proteins. Methods— The study included 237 individuals with history of ischemic stroke and 223 age-matched and gender-matched controls. The polymorphisms of the C-reactive protein ( CRP ), interleukin-6 ( IL-6 ), macrophage migration inhibitory factor ( MIF ), monocyte chemoattractant protein-1 ( MCP-1 ), intercellular adhesion molecule-1 ( ICAM-1 ), E-selectin ( E-sel ), and matrix metalloproteinase-3 ( MMP-3 ) genes were studied. Results— IL-6 GG, IL-6 GC, MCP-1 GG, ICAM-1 EE, E-sel AA, and MMP-3 5A5A genotypes were significantly and independently associated with stroke history. The odds of stroke increased with the number of high-risk genotypes: carrying 1 proinflammatory gene variant conferred a risk of 3.3 (1.6 to 6.9), whereas individuals concomitantly carrying 2 and 3 proinflammatory gene variants had adjusted odds ratios of 21.0 (7.6 to 57.5) and 50.3 (10.2 to 248.1), respectively. Conclusions— Proinflammatory genetic profiles are significantly more common in subjects with stroke history. Synergistic effects between proinflammatory genotypes might be potential markers for cerebrovascular diseases. more...
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- 2004
25. 1093. Ex Vivo Gene Therapy Approach Using Human Lim Mineralization Protein_3 To Induce Bone Healing in a Rodent Model
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Paul D. Robbins, Enrico Pola, Wanda Lattanzi, Anna Tampieri, Carlo Ambrogio Logroscino, Giandomenico Logroscino, Andrea Gambotto, and Giovanni Pecorini
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Pharmacology ,Pathology ,medicine.medical_specialty ,Cartilage ,Genetic enhancement ,Osteoblast ,Bone healing ,Anatomy ,Biology ,In vitro ,medicine.anatomical_structure ,Multiplicity of infection ,In vivo ,Drug Discovery ,Genetics ,medicine ,Molecular Medicine ,Molecular Biology ,Ex vivo - Abstract
Aims. Gene therapy research in the field of orthopaedics and traumatology have evolved during the last decade, leading to possible applications for the treatment of pathological conditions, such as bone fractures and cartilage defects. In particular, several gene transfer techniques have been employed so far for inducing bone formation in animal models of bone defects. Cell-based approaches, using in vitro and ex vivo genetically modified cells to be implanted in the animal, produced promising results as they enable the production of physiologic doses of an osteoinductive gene product into selected anatomical sites. In this study we used autologous skin fibroblasts, which are very simple to harvest and propagate in culture, transduced ex vivo with the new osteo-genic factor Lim Mineralization Factor-3 (Ad-LMP-3). These engineered cells produced successful bone healing when implanted by the use of a scaffold in rats, validating the in vivo osteoinductive properties of hLMP-3. Methods. Primary dermal fibroblasts cultures were established using a 1cm 2 biopsy of shaved skin obtained from the abdomen of each rat after anesthesia. Semi-confluent primary fibroblasts were infected with either AdBMP-2 or AdhLMP-3 or both, using a overall multiplicity of infection (MOI) of 100 viral particles per cell. Cells transduced with Ad-eGFP at the same MOI were used as a viral infection control, while untreated cells served as a negative control. The transduced cells were harvested 24 hours after viral infection, resuspended in sterile PBS, let adsorbed on a Hydroxyapatite/Collagen scaffold and then implanted in a bone defect surgically performed in the mandible of immunocompetent rats. The animals were divided in 4 groups: 9 rats were treated with cells infected with AdLMP-3, 9 rats with cells infected with AdBMP-2 (positive controls), 9 rats with cells transduced with Ad-eGFP and 9 rats with untreated cells (controls). 3 Rats from each group were sacrified at 1, 2 and 3 months after the treatment and studied by x-rays, Micro-CT and histology (Von kossa and Alizarin staining). Results. All the animals treated with LMP-3 showed healing of the bone defect after 3 months, as confirmed his-tologically and radiographically. On the contrary none of the controls showed bone formation at latest time point. Conclusions. Recently, Lim Mineralization Proteins (LMP), coded by three different splice variants (LMP-1, LMP-2, LMP-3) of the same gene, have been identified as regulators of the osteoblast differentiation program. We have previously demonstrated that human LMP-3 (hLMP-3) contributes actively to bone formation, acting at least in part, through the BMP-2 signaling pathway, being capable of inducing differentiation of cells of mes-enchymal derivation towards the osteoblastic lineage, through the up-regulation of bone-specific genes, along with ectopic bone formation in vivo and mineralization in vitro. In this study we have analyzed the efficacy of an ex-vivo approach using autologous dermal fibroblasts infected with AdLMP-3. Engineered cells produced bone healing when implanted by the use of a scaffold in a rodent model, validating the in vivo osteoinductive properties of hLMP-3. more...
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- 2006
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26. 897. The Development of Standards for Cell and Gene Therapy Products: The Activities of the United States Pharmacopeia
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Paul D. Robbins, Giuseppe Straface, Giovanni Pecorini, Carlo Ambrogio Logroscino, Wanda Lattanzi, Enrico Pola, Andrea Gambotto, and Pierangelo Papaleo
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Pharmacology ,Pathology ,medicine.medical_specialty ,Chemistry ,Ossification ,Anatomy ,Ectopic bone formation ,Bone morphogenetic protein 2 ,Green fluorescent protein ,Staining ,Nih3t3 fibroblast ,In vivo ,Drug Discovery ,Genetics ,medicine ,Molecular Medicine ,medicine.symptom ,Von Kossa stain ,Molecular Biology - Abstract
Top of pageAbstract Previous studies have demonstrated that the Bone Morphogenetic Protein-2 (BMP-2) induces bone formation in several animal models. In this study we have evaluated the capability of murine fibroblasts modified with BMP-2 to induce ectopic bone formation in vivo. First generation adenoviruses encoding either human bone morphogenetic protein-2 (BMP-2) or, as a negative control, enhanced green fluorescent protein (eGFP), have been used as vectors to introduce BMP-2 and eGFP genes in coltures of NIH3T3 fibroblast cells. The efficency of infection was evaluated by the fluorescence. Twenty-four hours after the infection the modified cells were pelleted, suspended in PBS and directly injected in the triceps muscle of immunocompetent mice. Development of ectopic bone formation was monitored radiographically for 3 weeks and representative specimens were evaluated histologically after 10, 15, 20 days by alizarin and von kossa staining. By radiological criteria, some of the animals receiving the BMP-2-modified fibroblasts developed ectopic bone formation already after 10 days, whereas all those receiving the eGFP-modified were negative. T 3 weeks half of the animals treated with BMP-2-modified fibroblasts developed bone in muscles. Histologic examination of representative mice at 10 days showed ossification in 50% of the muscles treated with the BMP-2-modified cells, as confirmed with the bone-specific staining. Instead, at the end of the 3-weeks experiment, the control muscles showed no radiological or histological signs of bone formation. This study suggests that direct, local delivery of BMP-2-modified fibroblasts could be a safe and powerful method to induce bone formation in vivo. These promising data encourage the further development of ex-vivo genetic approaches to enhancing bone formation in vivo. more...
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- 2004
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