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522 results on '"Martelli, Alma"'

155. Hydrogen sulfide inhalation ameliorates allergen induced airway hypereactivity by modulating mast cell activation

Author

Roviezzo, Fiorentina, primary, Bertolino, Antonio, additional, Sorrentino, Rosalinda, additional, Terlizzi, Michela, additional, Matteis, Maria, additional, Calderone, Vincenzo, additional, Mattera, Valentina, additional, Martelli, Alma, additional, Spaziano, Giuseppe, additional, Pinto, Aldo, additional, D’Agostino, Bruno, additional, and Cirino, Giuseppe, additional

Published
2015
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161. Pharmacological characterization of the vascular effects of aryl isothiocyanates: is hydrogen sulfide the real player?

Author

UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, Martelli, Alma, Testai, Lara, Citi, Valentina, Marino, Alice, Bellagambi, Francesca G, Ghimenti, Silvia, Breschi, Maria C, Calderone, Vincenzo, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, Martelli, Alma, Testai, Lara, Citi, Valentina, Marino, Alice, Bellagambi, Francesca G, Ghimenti, Silvia, Breschi, Maria C, and Calderone, Vincenzo

Abstract

Hydrogen sulfide (H₂S) is an endogenous gasotransmitter, which mediates important physiological effects in the cardiovascular system. Accordingly, an impaired production of endogenous H₂S contributes to the pathogenesis of important cardiovascular disorders, such as hypertension. Therefore, exogenous compounds, acting as H₂S-releasing agents, are viewed as promising pharmacotherapeutic agents for cardiovascular diseases. Thus, this paper aimed at evaluating the H₂S-releasing properties of some aryl isothiocyanate derivatives and their vascular effects. The release of H₂S was determined by amperometry, spectrophotometry and gas/mass chromatography. Moreover, the vascular activity of selected isothiocyanates were tested in rat conductance (aorta) and coronary arteries. Since H₂S has been recently reported to act as an activator of vascular Kv7 potassium channels, the possible membrane hyperpolarizing effects of isothiocyanates were tested on human vascular smooth muscle (VSM) cells by spectrofluorescent dyes. Among the tested compounds, phenyl isothiocyanate (PhNCS) and 4-carboxyphenyl isothiocyanate (PhNCS-COOH) exhibited slow-H₂S-release, triggered by organic thiols such as L-cysteine. These compounds were endowed with vasorelaxing effects on conductance and coronary arteries. Moreover, these two isothiocyanates caused membrane hyperpolarization of VSM cells. The vascular effects of isothiocyanates were strongly abolished by the selective Kv7-blocker XE991. In conclusion, the isothiocyanate function can be viewed as a suitable slow H₂S-releasing moiety, endowed with vasorelaxing and hypotensive effects, typical of this gasotransmitter. Thus, such a chemical moiety can be employed for the development of novel chemical tools for basic studies and promising cardiovascular drugs.

Published
2014

162. Hydrogen sulfide releasing capacity of natural isothiocyanates: is it a reliable explanation for the multiple biological effects of Brassicaceae?

Author

UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, Citi, Valentina, Martelli, Alma, Testai, Lara, Marino, Alice, Breschi, Maria C, Calderone, Vincenzo, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, Citi, Valentina, Martelli, Alma, Testai, Lara, Marino, Alice, Breschi, Maria C, and Calderone, Vincenzo

Abstract

Hydrogen sulfide is an endogenous pleiotropic gasotransmitter, which mediates important physiological effects in the human body. Accordingly, an impaired production of endogenous hydrogen sulfide contributes to the pathogenesis of important disorders. To date, exogenous compounds, acting as hydrogen sulfide-releasing agents, are viewed as promising pharmacotherapeutic agents. In a recent report, the hydrogen sulfide-releasing properties of some synthetic aryl isothiocyanate derivatives have been reported, indicating that the isothiocyanate function can be viewed as a suitable slow hydrogen sulfide-releasing moiety, endowed with the pharmacological potential typical of this gasotransmitter. Many isothiocyanate derivatives (deriving from a myrosinase-mediated transformation of glucosinolates) are well-known secondary metabolites of plants belonging to the family Brassicaceae, a large botanical family comprising many edible species. The phytotherapeutic and nutraceutic usefulness of Brassicaceae in the prevention of important human diseases, such as cancer, neurodegenerative processes and cardiovascular diseases has been widely discussed in the scientific literature. Although these effects have been largely attributed to isothiocyanates, the exact mechanism of action is still unknown. In this experimental work, we aimed to investigate the possible hydrogen sulfide-releasing capacity of some important natural isothiocyanates, studying it in vitro by amperometric detection. Some of the tested natural isothiocyanates exhibited significant hydrogen sulfide release, leading us to hypothesize that hydrogen sulfide may be, at least in part, a relevant player accounting for several biological effects of Brassicaceae.

Published
2014

180. Arylthioamides as H2S Donors: l-Cysteine-Activated Releasing Properties and Vascular Effects in Vitro and in Vivo.

Author

UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, Martelli, Alma, Testai, Lara, Citi, Valentina, Marino, Alice, Pugliesi, Isabella, Barresi, Elisabetta, Nesi, Giulia, Rapposelli, Simona, Taliani, Sabrina, Da Settimo, Federico, Breschi, Maria C, Calderone, Vincenzo, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, Martelli, Alma, Testai, Lara, Citi, Valentina, Marino, Alice, Pugliesi, Isabella, Barresi, Elisabetta, Nesi, Giulia, Rapposelli, Simona, Taliani, Sabrina, Da Settimo, Federico, Breschi, Maria C, and Calderone, Vincenzo

Abstract

A small library of arylthioamides 1-12 was easily synthesized, and their H2S-releasing properties were evaluated both in the absence or in the presence of an organic thiol such as l-cysteine. A number of arylthioamides (1-3 and 7) showed a slow and l-cysteine-dependent H2S-releasing mechanism, similar to that exhibited by the reference slow H2S-releasing agents, such as diallyl disulfide (DADS) and the phosphinodithioate derivative GYY 4137. Compound 1 strongly abolished the noradrenaline-induced vasoconstriction in isolated rat aortic rings and hyperpolarized the membranes of human vascular smooth muscle cells in a concentration-dependent fashion. Finally, a significant reduction of the systolic blood pressure of anesthetized normotensive rats was observed after its oral administration. Altogether these results highlighted the potential of arylthioamides 1-3 and 7 as H2S-donors for basic studies, and for the rational design/development of promising pharmacotherapeutic agents to treat cardiovascular diseases.

Published
2013

181. NSAID-Induced Enteropathy: Are the Currently Available Selective COX-2 Inhibitors All the Same?

Author

Fornai, Matteo, primary, Antonioli, Luca, additional, Colucci, Rocchina, additional, Pellegrini, Carolina, additional, Giustarini, Giulio, additional, Testai, Lara, additional, Martelli, Alma, additional, Matarangasi, Antuela, additional, Natale, Gianfranco, additional, Calderone, Vincenzo, additional, Tuccori, Marco, additional, Scarpignato, Carmelo, additional, and Blandizzi, Corrado, additional

Published
2013
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182. Arylthioamides as H2S Donors: l-Cysteine-Activated Releasing Properties and Vascular Effects in Vitro and in Vivo

Author

Martelli, Alma, primary, Testai, Lara, additional, Citi, Valentina, additional, Marino, Alice, additional, Pugliesi, Isabella, additional, Barresi, Elisabetta, additional, Nesi, Giulia, additional, Rapposelli, Simona, additional, Taliani, Sabrina, additional, Da Settimo, Federico, additional, Breschi, Maria C., additional, and Calderone, Vincenzo, additional

Published
2013
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183. Correction to Novel Analgesic/Anti-Inflammatory Agents: 1,5-Diarylpyrrole Nitrooxyalkyl Ethers and Related Compounds as Cyclooxygenase-2 Inhibiting Nitric Oxide Donors

Author

Anzini, Maurizio, primary, Di Capua, Angela, additional, Valenti, Salvatore, additional, Brogi, Simone, additional, Rovini, Michele, additional, Giuliani, Germano, additional, Cappelli, Andrea, additional, Vomero, Salvatore, additional, Chiasserini, Luisa, additional, Sega, Alessandro, additional, Poce, Giovanna, additional, Giorgi, Gianluca, additional, Calderone, Vincenzo, additional, Martelli, Alma, additional, Testai, Lara, additional, Sautebin, Lidia, additional, Rossi, Antonietta, additional, Pace, Simona, additional, Ghelardini, Carla, additional, Di Cesare Mannelli, Lorenzo, additional, Benetti, Veronica, additional, Giordani, Antonio, additional, Anzellotti, Paola, additional, Dovizio, Melania, additional, Patrignani, Paola, additional, and Biava, Mariangela, additional

Published
2013
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184. 1,4-Benzothiazine ATP-Sensitive Potassium Channel Openers: Modifications at the C-2 and C-6 Positions

Author

Martelli, Alma, primary, Manfroni, Giuseppe, additional, Sabbatini, Paola, additional, Barreca, Maria Letizia, additional, Testai, Lara, additional, Novelli, Michela, additional, Sabatini, Stefano, additional, Massari, Serena, additional, Tabarrini, Oriana, additional, Masiello, Pellegrino, additional, Calderone, Vincenzo, additional, and Cecchetti, Violetta, additional

Published
2013
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185. Novel Analgesic/Anti-Inflammatory Agents: 1,5-Diarylpyrrole Nitrooxyalkyl Ethers and Related Compounds as Cyclooxygenase-2 Inhibiting Nitric Oxide Donors

Author

Anzini, Maurizio, primary, Di Capua, Angela, additional, Valenti, Salvatore, additional, Brogi, Simone, additional, Rovini, Michele, additional, Giuliani, Germano, additional, Cappelli, Andrea, additional, Vomero, Salvatore, additional, Chiasserini, Luisa, additional, Sega, Alessandro, additional, Poce, Giovanna, additional, Giorgi, Gianluca, additional, Calderone, Vincenzo, additional, Martelli, Alma, additional, Testai, Lara, additional, Sautebin, Lidia, additional, Rossi, Antonietta, additional, Pace, Simona, additional, Ghelardini, Carla, additional, Di Cesare Mannelli, Lorenzo, additional, Benetti, Veronica, additional, Giordani, Antonio, additional, Anzellotti, Paola, additional, Dovizio, Melania, additional, Patrignani, Paola, additional, and Biava, Mariangela, additional

Published
2013
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186. The novel H2 S donor 4-carboxy-phenyl isothiocyanate inhibits mast cell degranulation and renin release by decreasing intracellular calcium.

Author

Marino, Alice, Martelli, Alma, Citi, Valentina, Fu, Ming, Wang, Rui, Calderone, Vincenzo, and Levi, Roberto

Subjects
*MAST cells, *ALLERGY treatment, *INTRACELLULAR calcium, *HYDROGEN sulfide, *PATHOLOGICAL physiology, *IMMUNOGLOBULIN E receptors, *THAPSIGARGIN, *IONOPHORES, *CALCIUM metabolism, *ANIMAL experimentation, *ANTI-infective agents, *CELL physiology, *MICE, *RATS, *RENIN, *RESEARCH funding, *PHYTOCHEMICALS, *CANCER cell culture, *PHARMACODYNAMICS
Abstract

Background and Purpose: Hydrogen sulfide (H2 S) modulates many pathophysiological processes, including inflammation and allergic reactions, in which mast cells act as major effector cells. IgE receptor (FcεRI) cross linking leads to an increase in intracellular calcium ([Ca+2 ]i ), a critical step in mast cell degranulation. The aim of this study was to investigate the role of H2 S in [Ca+2 ]i -dependent mast cell activation.Experimental Approach: We investigated the effects of H2 S, either endogenously produced or released by the slow H2 S donor 4-carboxy-phenyl isothiocyanate (PhNCS-COOH), on antigenic- and non-antigenic degranulation of native murine mast cells, and human and rat (RBL-2H3) mast cell lines. We measured the release of specific mast cell degranulation markers (β-hexosaminidase and renin), as well as changes in [Ca+2 ]i and phosphorylation of proteins downstream of FcεRI activation.Key Results: Endogenously produced H2 S inhibited antigen-induced degranulation in RBL-2H3. Similarly, H2 S released by PhNCS-COOH (10-300 μM) reduced, in a concentration-dependent manner, antigenic and non-antigenic degranulation and renin release in all mast cell types. Notably, PhNCS-COOH also prevented in a concentration-dependent mode the increase in [Ca+2 ]i elicited by Ca+2 ionophore, thapsigargin and FcεRI activation. Moreover, PhNCS-COOH attenuated the phosphorylation of Syk, cPLA-2 and PLCγ1 in antigen-stimulated RBL-2H3 cells.Conclusion and Implications: Collectively, our results demonstrate that, by attenuating the phosphorylation of proteins downstream of FcεRI cross-linking on mast cells, H2 S diminishes [Ca+2 ]i availability and thus mast cell degranulation and renin release. These findings suggest that PhNCS-COOH could be a strategic therapeutic tool in mast cell-mediated allergic conditions. [ABSTRACT FROM AUTHOR]

Published
2016
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187. Expression and function of Kv7.4 channels in rat cardiac mitochondria: possible targets for cardioprotection.

Author

Testai, Lara, Barrese, Vincenzo, Soldovieri, Maria Virginia, Ambrosino, Paolo, Martelli, Alma, Vinciguerra, Iolanda, Miceli, Francesco, Greenwood, Iain Andrew, Curtis, Michael John, Breschi, Maria Cristina, Sisalli, Maria Josè, Scorziello, Antonella, Canduela, Miren Josune, Grandes, Pedro, Calderone, Vincenzo, and Taglialatela, Maurizio

Subjects
POTASSIUM channels, HEART cells, MITOCHONDRIA, CARDIOLOGY, POLYMERASE chain reaction
Abstract

Aims: Plasmalemmal Kv7.1 (KCNQ1) channels are critical players in cardiac excitability; however, little is known on the functional role of additional Kv7 family members (Kv7.2-5) in cardiac cells. In this work, the expression, function, cellular and subcellular localization, and potential cardioprotective role against anoxic-ischaemic cardiac injury of Kv7.4 channels have been investigated. Methods and results: Expression of Kv7.1 and Kv7.4 transcripts was found in rat heart tissue by quantitative polymerase chain reaction.Western blots detected Kv7.4 subunits in mitochondria from Kv7.4-transfected cells, H9c2 cardiomyoblasts, freshly isolated adult cardiomyocytes, and whole hearts. Immunofluorescence experiments revealed that Kv7.4 subunits co-localized with mitochondrial markers in cardiac cells, with ~30-40% of cardiac mitochondria being labelled by Kv7.4 antibodies, a result also confirmed by immunogold electron microscopy experiments. In isolated cardiac (but not liver) mitochondria, retigabine (1-30 μM) and flupirtine (30 μM), two selective Kv7 activators, increased Tl+ influx, depolarized the membrane potential, and inhibited calcium uptake; all these effects were antagonized by the Kv7 blocker XE991. In intact H9c2 cells, reducing Kv7.4 expression by RNA interference blunted retigabine-induced mitochondrial membrane depolarization; in these cells, retigabine decreased mitochondrial Ca2+ levels and increased radical oxygen species production, both effects prevented by XE991. Finally, retigabine reduced cellular damage in H9c2 cells exposed to anoxia/ re-oxygenation and largely prevented the functional and morphological changes triggered by global ischaemia/reperfusion (I/R) in Langendorff-perfused rat hearts. Conclusion: Kv7.4 channels are present and functional in cardiac mitochondria; their activation exerts a significant cardioprotective role, making them potential therapeutic targets against I/R-induced cardiac injury. [ABSTRACT FROM AUTHOR]

Published
2016
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189. Novel Analgesic/Anti-Inflammatory Agents: Diarylpyrrole Acetic Esters Endowed with Nitric Oxide Releasing Properties

Author

Biava, Mariangela, primary, Porretta, Giulio Cesare, additional, Poce, Giovanna, additional, Battilocchio, Claudio, additional, Alfonso, Salvatore, additional, Rovini, Michele, additional, Valenti, Salvatore, additional, Giorgi, Gianluca, additional, Calderone, Vincenzo, additional, Martelli, Alma, additional, Testai, Lara, additional, Sautebin, Lidia, additional, Rossi, Antonietta, additional, Papa, Giuseppina, additional, Ghelardini, Carla, additional, Di Cesare Mannelli, Lorenzo, additional, Giordani, Antonio, additional, Anzellotti, Paola, additional, Bruno, Annalisa, additional, Patrignani, Paola, additional, and Anzini, Maurizio, additional

Published
2011
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199. New NO-Releasing Pharmacodynamic Hybrids of Losartan and Its Active Metabolite: Design, Synthesis, and Biopharmacological Properties

Author

Breschi, Maria C., primary, Calderone, Vincenzo, additional, Digiacomo, Maria, additional, Macchia, Marco, additional, Martelli, Alma, additional, Martinotti, Enrica, additional, Minutolo, Filippo, additional, Rapposelli, Simona, additional, Rossello, Armando, additional, Testai, Lara, additional, and Balsamo, Aldo, additional

Published
2006
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