30 results on '"Colombi B"'
Search Results
2. Efficacy and Limitations of Quinidine in Patients with Brugada Syndrome
- Author
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Mazzanti, A, Tenuta, E, Marino, M, Pagan, E, Morini, M, Memmi, M, Colombi, B, Tibollo, V, Frassoni, S, Curcio, A, Raimondo, C, Maltret, A, Monteforte, N, Bloise, R, Napolitano, C, Bellazzi, R, Bagnardi, V, Priori, S, Mazzanti, Andrea, Tenuta, Elisavietta, Marino, Maira, Pagan, Eleonora, Morini, Massimo, Memmi, Mirella, Colombi, Barbara, Tibollo, Valentina, Frassoni, Samuele, Curcio, Antonio, Raimondo, Cristina, Maltret, Alice, Monteforte, Nicola, Bloise, Raffaella, Napolitano, Carlo, Bellazzi, Riccardo, Bagnardi, Vincenzo, Priori, Silvia G., Mazzanti, A, Tenuta, E, Marino, M, Pagan, E, Morini, M, Memmi, M, Colombi, B, Tibollo, V, Frassoni, S, Curcio, A, Raimondo, C, Maltret, A, Monteforte, N, Bloise, R, Napolitano, C, Bellazzi, R, Bagnardi, V, Priori, S, Mazzanti, Andrea, Tenuta, Elisavietta, Marino, Maira, Pagan, Eleonora, Morini, Massimo, Memmi, Mirella, Colombi, Barbara, Tibollo, Valentina, Frassoni, Samuele, Curcio, Antonio, Raimondo, Cristina, Maltret, Alice, Monteforte, Nicola, Bloise, Raffaella, Napolitano, Carlo, Bellazzi, Riccardo, Bagnardi, Vincenzo, and Priori, Silvia G.
- Abstract
Background Quinidine at high dose is suggested as antiarrhythmic treatment in patients with Brugada Syndrome (BrS), but its efficacy to prevent life-threatening arrhythmic events (LAE) in this population is unproven and its use limited by frequent side effects. We assessed whether low-dose quinidine in patients with BrS reduces the following: (1) the occurrence of LAEs at follow-up, as compared to no therapy, in a population of both high-risk survivors of LAE and lower risk patients asymptomatic for LAEs and (2) the arrhythmic burden in the high-risk group of cardiac arrest survivors. Methods We compared the clinical course of 53 patients with BrS treated with quinidine to that of 441 untreated controls, matched by sex, age, symptoms, and the duration of observation. Furthermore, we calculated the annual incidence of LAE off-quinidine and on-quinidine in 123 patients with BrS who were cardiac arrest survivors. Results Fifty-three patients with BrS (89% males, median age 39.8 years) received quinidine (439±115 mg/d) for 5.0±3.7 years. Therapy was stopped in 3 cases (6%) for side effects. Quinidine reduced by 26% the risk of experiencing an LAE in cases versus controls (hazard ratio, 0.74; 95% CI, 0.22-2.48; P=0.62). Furthermore, in 27 of 123 patients with BrS symptomatic for LAEs who were treated for 7.0±3.5 years, the annual rate of LAEs decreased from 14.7% while off-quinidine to 3.9% while on-quinidine (P=0.03). Of note, recurrent LAEs were recorded in 4 (15%) cardiac arrest survivors while on-quinidine. Conclusions We demonstrated for the first time in the long-term that low-dose quinidine reduces recurrent LAEs in patients with BrS who had already survived an LAE, with few side effects. Remarkably, 15% of patients symptomatic for LAEs experience recurrent life-threatening arrhythmias while on-treatment, suggesting that quinidine cannot replace implantable defibrillators in high-risk subjects. Visual Overview A visual overview is available for this article.
- Published
- 2019
3. Efeito de compostos inibidores na bioconversão de glicose em etanol por levedura Saccharomyces cerevisiae
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COLOMBI, B. L., ORTIZ, M. A., ZANONI, P. R. S., MAGALHAES, W. L. E., TAVARES, L. B. B., Bruna Lyra Colombi, Universidade Regional de Blumenau, Marilha Almeida Ortiz, Universidade Regional de Blumenau, PATRICIA RAQUEL SILVA ZANONI, CNPF, WASHINGTON LUIZ ESTEVES MAGALHAES, CNPF, and Lorena Benathar Ballod Tavares, Universidade Regional de Blumenau.
- Subjects
Fermentação alcoólica ,Lignocellulosic ethanol ,Pré-tratamento ,Inibição ,Alcoholic fermentation ,Etanol lignocelulósico ,Pretreatment ,Inhibition - Abstract
Biomassas lignocelulósicas, como resíduos agrícolas e florestais, podem servir de matriz carbônica para a fermentação e obtenção do etanol de segunda geração (2G). Porém, os açúcares fermentescíveis não estão prontamente disponíveis, precisando ser liberados por operações adicionais de pré-tratamento e hidrólise. Paralelamente, substâncias químicas com potencial efeito inibitório ao metabolismo microbiano também são formadas e podem comprometer a produtividade e o rendimento global do processo. Esse estudo teve como objetivo avaliar a influência de vanilina, ácido acético, ácido vanílico e ácido 4-hidroxibenzoico na fermentação de glicose pela levedura Saccharomyces cerevisiae JP1. O cultivo ocorreu em meio sintético composto por nutrientes e 40 g.L-1 de glicose, inibidor em diferentes concentrações e 3% (v/v) de inóculo obtido em meio YPD líquido. O experimento foi conduzido a 30 °C e 150 rpm por 22 h. Amostras foram coletadas periodicamente para monitoramento da multiplicação celular e consumo de substrato, bem como quantificação de etanol no final do procedimento. Os resultados indicaram que vanilina (0,1; 0,5; 1,0 e 1,5 g.L-1) e ácido vanílico (0,1; 0,5 e 1,0 g.L-1) inibiram o crescimento da levedura em uma extensão diretamente proporcional à concentração inicial destes no meio fermentativo. O ácido 4-hidroxibenzoico apresentou, em média, 25% de toxicidade em relação ao crescimento celular, independente das quantidades estudadas (0,1; 0,5 e 1,0 g.L-1).
- Published
- 2017
4. Para além da flexibilização e intensificação do trabalho: notas sobre a discussão do termo precarização do trabalho
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COLOMBI, B. L. P., SALAZAR, S. N., MARQUES, R. M., and SABADINI, M. S.
- Abstract
Made available in DSpace on 2016-08-29T11:12:44Z (GMT). No. of bitstreams: 1 tese_6636_Barbara Leite Pereira.pdf: 723711 bytes, checksum: 5f53b845787767d7863281b178333aea (MD5) Previous issue date: 2013-06-12 Essa dissertação está vinculada à linha de pesquisa um do mestrado em Política Social da Universidade Federal do Espírito Santo denominada: Reprodução e estrutura do capitalismo contemporâneo. Seu objetivo principal é analisar do que se trata o fenômeno da precarização do trabalho no sistema capitalista de produção. Para atingir tal objetivo dividimos o trabalho em três capítulos: o primeiro deles procurou identificar se historicamente o modo de produção capitalista, em sua essência, deixou em algum momento histórico de apresentar traços característicos de precariedade. Já o segundo identificou como os autores brasileiros contemporâneos têm definido a precarização do trabalho, no intuito de contextualizar o leitor acerca do debate e, por último, houve uma averiguação da existência ou não de similaridade entre o termo precarização do trabalho com a flexibilidade e intensificação do trabalho, com o intuito de demonstrar a peculiaridade do termo precarização do trabalho. A hipótese dessa pesquisa é a consideração de que o capitalismo, da maneira como a história ilustra, impôs e impõe em suas relações de classes, sempre traços de fragilidade e precariedade para os trabalhadores. Esse é o ponto chave dessa dissertação.
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- 2013
5. Edible wild greens: a potentially rich source of antioxidants in the Italian diet
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Pellegrini, N, Frasca, G, Salvatore, S, Colombi, B, Brenna, O, Tumino, R, Del Rio, D, and Brighenti, F
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- 2003
6. Total antioxidant capacity of plant foods, beverages and oils consumed in Italy assessed by three different in vitro assays
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Pellegrini, N, Serafini, Mauro, Colombi, B, DEL RIO, D, Salvatore, S, and Bianchi, M. BRIGHENTI F.
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- 2003
7. Inflammatory trigeminal sensory neuropathy mimicking trigeminal neurinoma
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Rorick, M. B., primary, Chandar, K., additional, and Colombi, B. J., additional
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- 1996
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8. A thermodynamic approach for cooperative phenomena in magnetic materials
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Cavallotti, P.L., primary, Colombi, B., additional, Nobili, L., additional, Ossi, P.M., additional, and Colombo, M., additional
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- 1990
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9. Age and sex differences in human skeletal muscle: Role of reactive oxygen species.
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Pansarasa, O., Castagna, L., Colombi, B., Vecchiet, J., Felzani, G., and Marzatico, F.
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- 2000
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10. SOME EXPERIMENTS ON TRANSVERSE WAVES.
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SCARASCIA, S., COLOMBI, B., and CASSINIS, R.
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bstract [ABSTRACT FROM AUTHOR]
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- 1976
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11. RYR2 and CASQ2 mutations in patients suffering from catecholaminergic polymorphic ventricular tachycardia - Response
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Priori, Sg, Bolise, R., Mirella Memmi, Colombi, B., Napolitano, C., Coltorti, F., Keegan, R., Cruz, Fes, Drago, F., Viganti, G., Benatar, A., Simone, L., and Delogu, A.
12. Genotype/phenotype correlation in catecholaminergic ventricular tachycardia: evidence for heterogeneous clinical presentation
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Napolitano, C., Bloise, R., Mirella Memmi, Drago, F., Vignati, G., Colombi, B., Priori, Sg, and Simone, L.
13. Clinical and molecular characterization of a large cohort of patients affected by catecholaminergic polymorphic ventricular tachycardia
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Cerrone, M., Colombi, B., Bloise, R., Memmi, M., Moncalvo, C., Maugeri, Fs, Potenza, D., Drago, F., carlo napolitano, Bradley, Dj, and Priori, Sg
14. Gene-specific features of catecholaminergic polymorphic ventricular tachycardia: Implications for management
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Grillo, M., Napolitano, C., Bloise, R., Colombi, B., Mirella Memmi, Drago, F., Desimone, L., Gasparini, M., Keegan, R., Cruz, Fes, Delogu, A., and Priori, Sg
15. Phenotypic characterization of molecular defects of cardiac ryanodine receptor gene (RyR2)
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Napolitano, C., Priori, Sg, Vignati, G., Drago, F., Mirella Memmi, Colombi, B., and Grillo, M.
16. A deletion in the calsequestrin gene (CASQ2) causes the autosomal dominant form of catecholaminergic polymorphic ventricular tachycardia
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Napolitano, C., Mirella Memmi, Gasparini, M., Colombi, B., Bloise, R., Ronchetti, E., and Priori, Sg
17. Clinical and genetic heterogeneity of the right bundle branch block and ST-segment elevation syndrome. A prospective evaluation of 52 families
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Priori, Sg, Maurizio Gasparini, Napolitano, C., Pappone, C., Della Bella, P., Brignole, M., Giordano, U., Menozzi, C., Giovannini, T., Crotti, L., Colombi, B., and Schwartz, Pj
18. Efficacy and Limitations of Quinidine in Patients With Brugada Syndrome
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Andrea Mazzanti, Riccardo Bellazzi, Eleonora Pagan, Cristina Raimondo, Massimo Morini, Elisavietta Tenuta, Alice Maltret, Nicola Monteforte, Raffaella Bloise, Mirella Memmi, Barbara Colombi, Maira Marino, Vincenzo Bagnardi, Carlo Napolitano, Antonio Curcio, Samuele Frassoni, Valentina Tibollo, Silvia G. Priori, Mazzanti, A, Tenuta, E, Marino, M, Pagan, E, Morini, M, Memmi, M, Colombi, B, Tibollo, V, Frassoni, S, Curcio, A, Raimondo, C, Maltret, A, Monteforte, N, Bloise, R, Napolitano, C, Bellazzi, R, Bagnardi, V, and Priori, S
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Quinidine ,medicine.medical_specialty ,business.industry ,030204 cardiovascular system & hematology ,medicine.disease ,sudden cardiac death ,Sudden cardiac death ,cardiac arrhythmia ,03 medical and health sciences ,Antiarrhythmic drug ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,Cardiology ,Medicine ,Brugada syndrome ,In patient ,030212 general & internal medicine ,Cardiology and Cardiovascular Medicine ,business ,quinidine ,medicine.drug - Abstract
Background:Quinidine at high dose is suggested as antiarrhythmic treatment in patients with Brugada Syndrome (BrS), but its efficacy to prevent life-threatening arrhythmic events (LAE) in this population is unproven and its use limited by frequent side effects. We assessed whether low-dose quinidine in patients with BrS reduces the following: (1) the occurrence of LAEs at follow-up, as compared to no therapy, in a population of both high-risk survivors of LAE and lower risk patients asymptomatic for LAEs and (2) the arrhythmic burden in the high-risk group of cardiac arrest survivors.Methods:We compared the clinical course of 53 patients with BrS treated with quinidine to that of 441 untreated controls, matched by sex, age, symptoms, and the duration of observation. Furthermore, we calculated the annual incidence of LAE off-quinidine and on-quinidine in 123 patients with BrS who were cardiac arrest survivors.Results:Fifty-three patients with BrS (89% males, median age 39.8 years) received quinidine (439±115 mg/d) for 5.0±3.7 years. Therapy was stopped in 3 cases (6%) for side effects. Quinidine reduced by 26% the risk of experiencing an LAE in cases versus controls (hazard ratio, 0.74; 95% CI, 0.22–2.48;P=0.62). Furthermore, in 27 of 123 patients with BrS symptomatic for LAEs who were treated for 7.0±3.5 years, the annual rate of LAEs decreased from 14.7% while off-quinidine to 3.9% while on-quinidine (P=0.03). Of note, recurrent LAEs were recorded in 4 (15%) cardiac arrest survivors while on-quinidine.Conclusions:We demonstrated for the first time in the long-term that low-dose quinidine reduces recurrent LAEs in patients with BrS who had already survived an LAE, with few side effects. Remarkably, 15% of patients symptomatic for LAEs experience recurrent life-threatening arrhythmias while on-treatment, suggesting that quinidine cannot replace implantable defibrillators in high-risk subjects.
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- 2019
19. Unexpected structural and functional consequences of the R33Q homozygous mutation in cardiac calsequestrin: a complex arrhythmogenic cascade in a knock in mouse model
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Diego Arcelli, Pompeo Volpe, Feliciano Protasi, Alessandra Nori, Laura Villani, Alessandro Spedito, Carlo Napolitano, Nian Liu, Simona Boncompagni, Silvio Bicciato, Silvia G. Priori, Nicoletta Rizzi, Federica Turcato, Barbara Colombi, Mario Scelsi, Giovanni Esposito, Rizzi, N, Liu, N, Napolitano, C, Nori, A, Turcato, F, Colombi, B, Bicciato, S, Arcelli, D, Spedito, A, Scelsi, M, Villani, L, Esposito, Giovanni, Boncompagni, S, Protasi, F, Volpe, P, and Priori, S. G.
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medicine.medical_specialty ,Physiology ,Mutation, Missense ,Mice, Transgenic ,Biology ,Calsequestrin ,Catecholaminergic polymorphic ventricular tachycardia ,Ryanodine receptor 2 ,Sudden death ,Afterdepolarization ,Mice ,Internal medicine ,medicine ,Animals ,Ryanodine receptor ,Homozygote ,Arrhythmias, Cardiac ,medicine.disease ,Phospholamban ,Electrophysiology ,Disease Models, Animal ,Sarcoplasmic Reticulum ,Phenotype ,Endocrinology ,Triadin ,Calcium ,Cardiology and Cardiovascular Medicine - Abstract
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disorder characterized by life threatening arrhythmias elicited by physical and emotional stress in young individuals. The recessive form of CPVT is associated with mutation in the cardiac calsequestrin gene ( CASQ2 ). We engineered and characterized a homozygous CASQ2 R33Q/R33Q mouse model that closely mimics the clinical phenotype of CPVT patients. CASQ2 R33Q/R33Q mice develop bidirectional VT on exposure to environmental stress whereas CASQ2 R33Q/R33Q myocytes show reduction of the sarcoplasmic reticulum (SR) calcium content, adrenergically mediated delayed (DADs) and early (EADs) afterdepolarizations leading to triggered activity. Furthermore triadin, junctin, and CASQ2-R33Q proteins are significantly decreased in knock-in mice despite normal levels of mRNA, whereas the ryanodine receptor (RyR2), calreticulin, phospholamban, and SERCA2a-ATPase are not changed. Trypsin digestion studies show increased susceptibility to proteolysis of mutant CASQ2. Despite normal histology, CASQ2 R33Q/R33Q hearts display ultrastructural changes such as disarray of junctional electron-dense material, referable to CASQ2 polymers, dilatation of junctional SR, yet normal total SR volume. Based on the foregoings, we propose that the phenotype of the CASQ2 R33Q/R33Q CPVT mouse model is portrayed by an unexpected set of abnormalities including (1) reduced CASQ2 content, possibly attributable to increased degradation of CASQ2-R33Q, (2) reduction of SR calcium content, (3) dilatation of junctional SR, and (4) impaired clustering of mutant CASQ2.
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- 2008
20. Calmodulin kinase II inhibition prevents arrhythmias in RyR2(R4496C+/-) mice with catecholaminergic polymorphic ventricular tachycardia.
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Liu N, Ruan Y, Denegri M, Bachetti T, Li Y, Colombi B, Napolitano C, Coetzee WA, and Priori SG
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- Animals, Benzylamines pharmacology, Blotting, Western, Caffeine pharmacology, Calcium metabolism, Electrophysiology, Epinephrine pharmacology, Mice, Myocytes, Cardiac drug effects, Myocytes, Cardiac metabolism, Ryanodine Receptor Calcium Release Channel genetics, Sulfonamides pharmacology, Arrhythmias, Cardiac metabolism, Arrhythmias, Cardiac prevention & control, Calcium-Calmodulin-Dependent Protein Kinase Type 2 antagonists & inhibitors, Ryanodine Receptor Calcium Release Channel metabolism, Tachycardia metabolism
- Abstract
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease characterized by life-threatening arrhythmias elicited by adrenergic activation. CPVT is caused by mutations in the cardiac ryanodine receptor gene (RyR2). In vitro studies demonstrated that RyR2 mutations respond to sympathetic activation with an abnormal diastolic Ca(2+) leak from the sarcoplasmic reticulum; however the pathways that mediate the response to adrenergic stimulation have not been defined. In our RyR2(R4496C+/-) knock-in mouse model of CPVT we tested the hypothesis that inhibition of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) counteracts the effects of adrenergic stimulation resulting in an antiarrhythmic activity. CaMKII inhibition with KN-93 completely prevented catecholamine-induced sustained ventricular tachyarrhythmia in RyR2(R4496C+/-) mice, while the inactive congener KN-92 had no effect. In ventricular myocytes isolated from the hearts of RyR2(R4496C+/-) mice, CaMKII inhibition with an autocamtide-2 related inhibitory peptide or with KN-93 blunted triggered activity and transient inward currents induced by isoproterenol. Isoproterenol also enhanced the activity of the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), increased spontaneous Ca(2+) release and spark frequency. CaMKII inhibition blunted each of these parameters without having an effect on the SR Ca(2+) content. Our data therefore indicate that CaMKII inhibition is an effective intervention to prevent arrhythmogenesis (both in vivo and in vitro) in the RyR2(R4496C+/-) knock-in mouse model of CPVT. Mechanistically, CAMKII inhibition acts on several elements of the EC coupling cascade, including an attenuation of SR Ca(2+) leak and blunting catecholamine-mediated SERCA activation. CaMKII inhibition may therefore represent a novel therapeutic target for patients with CPVT., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
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- 2011
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21. Increased Ca2+ sensitivity of the ryanodine receptor mutant RyR2R4496C underlies catecholaminergic polymorphic ventricular tachycardia.
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Fernández-Velasco M, Rueda A, Rizzi N, Benitah JP, Colombi B, Napolitano C, Priori SG, Richard S, and Gómez AM
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- Adrenergic beta-Agonists pharmacology, Animals, Caffeine pharmacology, Cardiac Pacing, Artificial, Female, Isoproterenol pharmacology, Male, Membrane Potentials, Mice, Mice, Transgenic, Microscopy, Confocal, Myocytes, Cardiac drug effects, Phosphorylation, Ryanodine Receptor Calcium Release Channel genetics, Sarcoplasmic Reticulum metabolism, Tachycardia, Ventricular genetics, Tachycardia, Ventricular physiopathology, Time Factors, Calcium Signaling drug effects, Catecholamines metabolism, Mutation, Myocardial Contraction drug effects, Myocytes, Cardiac metabolism, Ryanodine Receptor Calcium Release Channel metabolism, Tachycardia, Ventricular metabolism
- Abstract
Cardiac ryanodine receptor (RyR2) mutations are associated with autosomal dominant catecholaminergic polymorphic ventricular tachycardia, suggesting that alterations in Ca(2+) handling underlie this disease. Here we analyze the underlying Ca(2+) release defect that leads to arrhythmia in cardiomyocytes isolated from heterozygous knock-in mice carrying the RyR2(R4496C) mutation. RyR2(R4496C-/-) littermates (wild type) were used as controls. [Ca(2+)](i) transients were obtained by field stimulation in fluo-3-loaded cardiomyocytes and viewed using confocal microscopy. In our basal recording conditions (2-Hz stimulation rate), [Ca(2+)](i) transients and sarcoplasmic reticulum Ca(2+) load were similar in wild-type and RyR2(R4496C) cells. However, paced RyR2(R4496C) ventricular myocytes presented abnormal Ca(2+) release during the diastolic period, viewed as Ca(2+) waves, consistent with the occurrence of delayed afterdepolarizations. The occurrence of this abnormal Ca(2+) release was enhanced at faster stimulation rates and by beta-adrenergic stimulation, which also induced triggered activity. Spontaneous Ca(2+) sparks were more frequent in RyR2(R4496C) myocytes, indicating increased RyR2(R4496C) activity. When permeabilized cells were exposed to different cytosolic [Ca(2+)](i), RyR2(R4496C) showed a dramatic increase in Ca(2+) sensitivity. Isoproterenol increased [Ca(2+)](i) transient amplitude and Ca(2+) spark frequency to the same extent in wild-type and RyR2(R4496C) cells, indicating that the beta-adrenergic sensitivity of RyR2(R4496C) cells remained unaltered. This effect was independent of protein expression variations because no difference was found in the total or phosphorylated RyR2 expression levels. In conclusion, the arrhythmogenic potential of the RyR2(R4496C) mutation is attributable to the increased Ca(2+) sensitivity of RyR2(R4496C), which induces diastolic Ca(2+) release and lowers the threshold for triggered activity.
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- 2009
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22. Unexpected structural and functional consequences of the R33Q homozygous mutation in cardiac calsequestrin: a complex arrhythmogenic cascade in a knock in mouse model.
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Rizzi N, Liu N, Napolitano C, Nori A, Turcato F, Colombi B, Bicciato S, Arcelli D, Spedito A, Scelsi M, Villani L, Esposito G, Boncompagni S, Protasi F, Volpe P, and Priori SG
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- Animals, Arrhythmias, Cardiac etiology, Calcium analysis, Calsequestrin physiology, Disease Models, Animal, Electrophysiology, Homozygote, Mice, Mice, Transgenic, Phenotype, Sarcoplasmic Reticulum chemistry, Arrhythmias, Cardiac genetics, Calsequestrin genetics, Mutation, Missense physiology
- Abstract
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disorder characterized by life threatening arrhythmias elicited by physical and emotional stress in young individuals. The recessive form of CPVT is associated with mutation in the cardiac calsequestrin gene (CASQ2). We engineered and characterized a homozygous CASQ2(R33Q/R33Q) mouse model that closely mimics the clinical phenotype of CPVT patients. CASQ2(R33Q/R33Q) mice develop bidirectional VT on exposure to environmental stress whereas CASQ2(R33Q/R33Q) myocytes show reduction of the sarcoplasmic reticulum (SR) calcium content, adrenergically mediated delayed (DADs) and early (EADs) afterdepolarizations leading to triggered activity. Furthermore triadin, junctin, and CASQ2-R33Q proteins are significantly decreased in knock-in mice despite normal levels of mRNA, whereas the ryanodine receptor (RyR2), calreticulin, phospholamban, and SERCA2a-ATPase are not changed. Trypsin digestion studies show increased susceptibility to proteolysis of mutant CASQ2. Despite normal histology, CASQ2(R33Q/R33Q) hearts display ultrastructural changes such as disarray of junctional electron-dense material, referable to CASQ2 polymers, dilatation of junctional SR, yet normal total SR volume. Based on the foregoings, we propose that the phenotype of the CASQ2(R33Q/R33Q) CPVT mouse model is portrayed by an unexpected set of abnormalities including (1) reduced CASQ2 content, possibly attributable to increased degradation of CASQ2-R33Q, (2) reduction of SR calcium content, (3) dilatation of junctional SR, and (4) impaired clustering of mutant CASQ2.
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- 2008
- Full Text
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23. Catecholaminergic polymorphic ventricular tachycardia.
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Liu N, Colombi B, Raytcheva-Buono EV, Bloise R, and Priori SG
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- Adult, Arousal physiology, Calsequestrin genetics, Chromosome Aberrations, Diagnosis, Differential, Genes, Dominant, Genes, Recessive, Genetic Predisposition to Disease genetics, Humans, Ryanodine Receptor Calcium Release Channel genetics, Tachycardia, Ventricular genetics, Catecholamines physiology, Death, Sudden, Cardiac etiology, Electrocardiography, Tachycardia, Ventricular physiopathology
- Abstract
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly lethal form of inherited arrhythmogenic disease characterized by adrenergically mediated polymorphic ventricular tachycardia. The mutations in cardiac ryanodine receptor and calsequestrin genes are responsible for the autosomal dominant and recessive variants of CPVT, respectively. The clinical presentation encompasses exercise- or emotion-induced syncopal events and a distinctive pattern of reproducible, stress-related, bidirectional ventricular tachycardia in the absence of both structural heart disease and a prolonged QT interval. The mortality rate in untreated individuals is 30-50% by age 40. Clinical evaluation by exercise stress testing and holter monitoring and genetic screening can facilitate early diagnosis. beta-adrenergic blockers are the most effective pharmacological treatment in controlling arrhythmias in CPVT patients, yet about 30% of patients still experience cardiac arrhythmias and eventually require an implantable cardioverter defibrillator.
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- 2007
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24. Arrhythmogenesis in catecholaminergic polymorphic ventricular tachycardia: insights from a RyR2 R4496C knock-in mouse model.
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Liu N, Colombi B, Memmi M, Zissimopoulos S, Rizzi N, Negri S, Imbriani M, Napolitano C, Lai FA, and Priori SG
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- Animals, Caffeine pharmacology, Cells, Cultured, Epinephrine pharmacology, Membrane Potentials, Mice, Mice, Mutant Strains, Myocytes, Cardiac physiology, Protein Binding, Ryanodine pharmacology, Ryanodine Receptor Calcium Release Channel metabolism, Tacrolimus Binding Proteins metabolism, Thiazepines pharmacology, Arrhythmias, Cardiac etiology, Mutation, Missense, Ryanodine Receptor Calcium Release Channel genetics, Tachycardia, Ventricular etiology
- Abstract
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by life threatening arrhythmias and mutations in the gene encoding the ryanodine receptor (RyR2). Disagreement exists on whether (1) RyR2 mutations induce abnormal calcium transients in the absence of adrenergic stimulation; (2) decreased affinity of mutant RyR2 for FKBP12.6 causes CPVT; (3) K201 prevent arrhythmias by normalizing the FKBP12.6-RyR2 binding. We studied ventricular myocytes isolated from wild-type (WT) and knock-in mice harboring the R4496C mutation (RyR2(R4496C+/-)). Pacing protocols did not elicit delayed afterdepolarizations (DADs) (n=20) in WT but induced DADs in 21 of 33 (63%) RyR2(R4496C+/-) myocytes (P=0.001). Superfusion with isoproterenol (30 nmol/L) induced small DADs (45%) and no triggered activity in WT myocytes, whereas it elicited DADs in 87% and triggered activity in 60% of RyR2(R4496C+/-) myocytes (P=0.001). DADs and triggered activity were abolished by ryanodine (10 micromol/L) but not by K201 (1 micromol/L or 10 micromol/L). In vivo administration of K201 failed to prevent induction of polymorphic ventricular tachycardia (VT) in RyR2(R4496C+/-) mice. Measurement of the FKBP12.6/RyR2 ratio in the heavy sarcoplasmic reticulum membrane showed normal RyR2-FKBP12.6 interaction both in WT and RyR2(R4496C+/-) either before and after treatment with caffeine and epinephrine. We suggest that (1) triggered activity is the likely arrhythmogenic mechanism of CPVT; (2) K201 fails to prevent DADs in RyR2(R4496C+/-) myocytes and ventricular arrhythmias in RyR2(R4496C+/-) mice; and (3) RyR2-FKBP12.6 interaction in RyR2(R4496C+/-) is identical to that of WT both before and after epinephrine and caffeine, thus suggesting that it is unlikely that the R4496C mutation interferes with the RyR2/FKBP12.6 complex.
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- 2006
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25. Bidirectional ventricular tachycardia and fibrillation elicited in a knock-in mouse model carrier of a mutation in the cardiac ryanodine receptor.
- Author
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Cerrone M, Colombi B, Santoro M, di Barletta MR, Scelsi M, Villani L, Napolitano C, and Priori SG
- Subjects
- Animals, Caffeine pharmacology, Electrocardiography, Epinephrine pharmacology, Mice, Tachycardia, Ventricular prevention & control, Ventricular Fibrillation prevention & control, Disease Models, Animal, Mutation, Ryanodine Receptor Calcium Release Channel genetics, Tachycardia, Ventricular genetics, Ventricular Fibrillation genetics
- Abstract
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by adrenergically mediated polymorphic ventricular tachycardia leading to syncope and sudden cardiac death. The autosomal dominant form of CPVT is caused by mutations in the RyR2 gene encoding the cardiac isoform of the ryanodine receptor. In vitro functional characterization of mutant RyR2 channels showed altered behavior on adrenergic stimulation and caffeine administration with enhanced calcium release from the sarcoplasmic reticulum. As of today no experimental evidence is available to demonstrate that RyR2 mutations can reproduce the arrhythmias observed in CPVT patients. We developed a conditional knock-in mouse model carrier of the R4496C mutation, the mouse equivalent to the R4497C mutations identified in CPVT families, to evaluate if the animals would develop a CPVT phenotype and if beta blockers would prevent arrhythmias. Twenty-six mice (12 wild-type (WT) and 14RyR(R4496C)) underwent exercise stress testing followed by epinephrine administration: none of the WT developed ventricular tachycardia (VT) versus 5/14 RyR(R4496C) mice (P=0.02). Twenty-one mice (8 WT, 8 RyR(R4496C), and 5 RyR(R4496C) pretreated with beta-blockers) received epinephrine and caffeine: 4/8 (50%) RyR(R4496C) mice but none of the WT developed VT (P=0.02); 4/5 RyR(R4496C) mice pretreated with propranolol developed VT (P=0.56 nonsignificant versus RyR(R4496C) mice). These data provide the first experimental demonstration that the R4496C RyR2 mutation predisposes the murine heart to VT and VF in response caffeine and/or adrenergic stimulation. Furthermore, the results show that analogous to what is observed in patients, beta adrenergic stimulation seems ineffective in preventing life-threatening arrhythmias.
- Published
- 2005
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26. Total antioxidant capacity of plant foods, beverages and oils consumed in Italy assessed by three different in vitro assays.
- Author
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Pellegrini N, Serafini M, Colombi B, Del Rio D, Salvatore S, Bianchi M, and Brighenti F
- Subjects
- Alcoholic Beverages, Chromans, Coffee chemistry, Ferric Compounds metabolism, Free Radical Scavengers, Humans, Italy, Methods, Oxidation-Reduction, Tea chemistry, Antioxidants analysis, Beverages, Dietary Fats, Unsaturated, Fruit chemistry, Vegetables chemistry
- Abstract
Epidemiologic studies have demonstrated an inverse association between consumption of fruits and vegetables and morbidity and mortality from degenerative diseases. The antioxidant content of fruits and vegetables may contribute to the protection they offer from disease. Because plant foods contain many different classes and types of antioxidants, knowledge of their total antioxidant capacity (TAC), which is the cumulative capacity of food components to scavenge free radicals, would be useful for epidemiologic purposes. To accomplish this, a variety of foods commonly consumed in Italy, including 34 vegetables, 30 fruits, 34 beverages and 6 vegetable oils, were analyzed using three different assays, i.e., Trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP) and ferric reducing-antioxidant power (FRAP). These assays, based on different chemical mechanisms, were selected to take into account the wide variety and range of action of antioxidant compounds present in actual foods. Among vegetables, spinach had the highest antioxidant capacity in the TEAC and FRAP assays followed by peppers, whereas asparagus had the greatest antioxidant capacity in the TRAP assay. Among fruits, the highest antioxidant activities were found in berries (i.e., blackberry, redcurrant and raspberry) regardless of the assay used. Among beverages, coffee had the greatest TAC, regardless of the method of preparation or analysis, followed by citrus juices, which exhibited the highest value among soft beverages. Finally, of the oils, soybean oil had the highest antioxidant capacity, followed by extra virgin olive oil, whereas peanut oil was less effective. Such data, coupled with an appropriate questionnaire to estimate antioxidant intake, will allow the investigation of the relation between dietary antioxidants and oxidative stress-induced diseases.
- Published
- 2003
- Full Text
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27. Rapid fluorimetric method to detect total plasma malondialdehyde with mild derivatization conditions.
- Author
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Del Rio D, Pellegrini N, Colombi B, Bianchi M, Serafini M, Torta F, Tegoni M, Musci M, and Brighenti F
- Subjects
- Circular Dichroism, Humans, Indicators and Reagents, Malondialdehyde chemistry, Spectrometry, Fluorescence, Thiobarbiturates chemistry, Malondialdehyde blood
- Published
- 2003
- Full Text
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28. Application of the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation assay to a flow injection system for the evaluation of antioxidant activity of some pure compounds and beverages.
- Author
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Pellegrini N, Del Rio D, Colombi B, Bianchi M, and Brighenti F
- Subjects
- Antioxidants chemistry, Beer analysis, Benzothiazoles, Carbonated Beverages analysis, Cations, Chromans analysis, Citrus, Coffee chemistry, Fruit chemistry, Indicators and Reagents, Quality Control, Sensitivity and Specificity, Solutions, Spectrophotometry, Tea chemistry, Antioxidants analysis, Beverages analysis, Flow Injection Analysis, Free Radicals chemistry, Sulfonic Acids chemistry
- Abstract
The 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS(*)(+)) assay was adapted to a flow injection (FI) system to obtain a sensitive and rapid technique for the monitoring of antioxidant activity of pure compounds and complex matrixes, such as beverages and food extracts. The FI system includes a HPLC pump that flows the mobile phase (a solution of ABTS(*)(+) in ethanol) through a 20 microL loop injector, a single bead string reactor filled with acid-washed silanized beads, a delay coil and a photodiode array UV-visible detector. The technique was very sensitive, with limits of detection and of quantification of 4.14 and 9.29 micromol of Trolox/L, respectively, and demonstrated high repeatability and reproducibility. The proposed technique was then applied to the evaluation of the antioxidant activity of some pure compounds, demonstrating good agreement with published data obtained by the original spectrophotometric ABTS(*)(+) assay. Finally, the total antioxidant activity of 10 beverages was determined by both the proposed and the original method. The values ranged from 0.09 mmol L(-)(1) for cola to 49.24 mmol L(-)(1) for espresso coffee and did not result significantly different from those obtained by the original spectrophotometric ABTS(*)(+) assay (Student's paired t-test: t = 1.4074, p = 0.1929). In conclusion, the proposed FI technique seems suitable for the direct, rapid and reliable monitoring of total antioxidant activity of pure compounds and beverages and, due to the ability to operate in continuous, it allows the analysis of about 30 samples h(-)(1) making the assay particularly suitable for large screening of total antioxidant activity in food samples.
- Published
- 2003
- Full Text
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29. Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia.
- Author
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Priori SG, Napolitano C, Memmi M, Colombi B, Drago F, Gasparini M, DeSimone L, Coltorti F, Bloise R, Keegan R, Cruz Filho FE, Vignati G, Benatar A, and DeLogu A
- Subjects
- Adolescent, Adult, Amino Acid Sequence, Catecholamines, Child, Child, Preschool, Death, Sudden, Cardiac epidemiology, Family Health, Female, Genetic Variation, Genotype, Humans, Male, Pedigree, Sequence Alignment, Survival Rate, Tachycardia, Ventricular mortality, Tachycardia, Ventricular therapy, Mutation, Ryanodine Receptor Calcium Release Channel genetics, Tachycardia, Ventricular diagnosis, Tachycardia, Ventricular genetics
- Abstract
Background: Mutations in the cardiac ryanodine receptor gene (RyR2) underlie catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmogenic disease occurring in the structurally intact heart. The proportion of patients with CPVT carrying RyR2 mutations is unknown, and the clinical features of RyR2-CPVT as compared with nongenotyped CPVT are undefined., Methods and Results: Patients with documented polymorphic ventricular arrhythmias occurring during physical or emotional stress with a normal heart entered the study. The clinical phenotype of the 30 probands and of 118 family members was evaluated, and mutation screening on the RyR2 gene was performed. Arrhythmias documented in probands were: 14 of 30 bidirectional ventricular tachycardia, 12 of 30 polymorphic ventricular tachycardia, and 4 of 30 catecholaminergic idiopathic ventricular fibrillation; RyR2 mutations were identified in 14 of 30 probands (36% bidirectional ventricular tachycardia, 58% polymorphic ventricular tachycardia, 50% catecholaminergic idiopathic ventricular fibrillation) and in 9 family members (4 silent gene carriers). Genotype-phenotype analysis showed that patients with RyR2 CPVT have events at a younger age than do patients with nongenotyped CPVT and that male sex is a risk factor for syncope in RyR2-CPVT (relative risk=4.2)., Conclusions: CPVT is a clinically and genetically heterogeneous disease manifesting beyond pediatric age with a spectrum of polymorphic arrhythmias. beta-Blockers reduce arrhythmias, but in 30% of patients an implantable defibrillator may be required. Genetic analysis identifies two groups of patients: Patients with nongenotyped CPVT are predominantly women and become symptomatic later in life; patients with RyR2 CPVT become symptomatic earlier, and men are at higher risk of cardiac events. These data provide a rationale for prompt evaluation and treatment of young men with RyR2 mutations.
- Published
- 2002
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30. The danger of intracranial wood.
- Author
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Miller CF, Brodkey JS, and Colombi BJ
- Subjects
- Adolescent, Adult, Brain Abscess etiology, Brain Injuries mortality, Brain Injuries surgery, Child, Child, Preschool, Eye Injuries complications, Female, Foreign Bodies mortality, Foreign Bodies surgery, Humans, Male, Orbit, Suicide, Attempted, Wounds, Stab mortality, Brain Injuries etiology, Foreign Bodies complications, Wood, Wounds, Stab complications
- Abstract
Peri-orbital puncture wounds by sharp wooden objects are not rare, but can be dangerous when there is intracranial penetration by and retention of the wooden foreign body. Days to years after an apparently trivial initial wounding, serious intracranial complications can occur. The authors have reviewed 42 case reports from the literature. Morbidity-defined as permanent neurologic sequelae-occurred in 74% of the cases. Intracranial suppuration was the major complication, with brain abscess having occurred in nearly one-half of the cases. Mortality occurred in 25% of 28 cases occurring in the post-antibiotic era. The qualities of wood which make it especially hazardous as a wounding agent and foreign body are discussed. The role of orbital anatomy in affording easy access to the cranial contents is described. Surgical exploration in all those cases in which there is a reasonable suspicion of intracranial injury is recommended.
- Published
- 1977
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