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Featured researches published by M. Lupini.


Inflammation Research | 1991

The effect of nitric oxide generators on ischemia reperfusion injury and histamine release in isolated perfused guinea-pig heart.

Emanuela Masini; Stefano Bianchi; Laura Mugnai; F. Gambassi; M. Lupini; A. Pistelli; P. F. Mannaioni

Experiments were carried out to provide evidence of the effect ofl-arginine (l-Arg), its analogue NG-monomethyl-l-arginine (MeArg) and of some nitrovasodilators (sodium nitroprusside, NaNP; 3-morpholino-sydnonimine, SIN-1) which spontaneously release nitric oxide (NO) on ischemia-reperfusion injury, histamine release and mast cell degranulation, occurring after multiple ligature and release of the left anterior descending (LAD) coronary artery in isolated perfused guinea-pig hearts. The reopening of the LAD coronary artery leads to a release of histamine related to a decrease in microdensitometry of cardiac mast cells and to calcium overload. The perfusion of the heart with NO-donors significantly reduces either the release of histamine, the loss of mast cell metachromasia and the overload of calcium. These effects were potentiated by SOD. The results suggest that the endogenous formation of NO and molecules able to generate NO have a role in the prevention of post-ischemic tissue injury.


British Journal of Pharmacology | 1995

Polydeoxyribonucleotides and nitric oxide release from guinea-pig hearts during ischaemia and reperfusion

Emanuela Masini; M. Lupini; Laura Mugnai; Silvia Raspanti; P. F. Mannaioni

1 Two polydeoxyribonucleotides, produced by the controlled hydrolysis of DNA of mammalian lung (defibrotide and its lower molecular weight fraction, P.O. 085 DV), were studied for their ability to modify the release of nitrite and the coronary flow in perfusates collected from isolated, normally perfused hearts of guinea‐pigs and from hearts subjected to regional ischaemia and reperfusion. 2 In guinea‐pig normally perfused hearts, both defibrotide (DFT) and its fraction, P.O. 085 DV, increase the amount of nitrite appearing in perfusates in a concentration‐dependent fashion. At the highest concentration studied (10−6 m), P.O. 085 DV was more effective than DFT. A concomitant increase in the coronary flow was observed. 3 The increase in nitrite in perfusates and the increase in coronary flow induced by both DFT and P.O. 085 DV were significantly reduced by NGmonomethyl‐L‐arginine (l‐NMMA, 10−4 m), an inhibitor of nitric oxide synthase (NOS). 4 The endothelium‐dependent vasodilator, acetylcholine (ACh), enhances the formation of nitrite and the coronary flow. Both the increase in coronary flow and in the formation of nitrite were significantly reduced by L‐NMMA (10−4 m). 5 In guinea‐pig hearts subjected to ischaemia and reperfusion, the effect of both compounds in increasing the amount of nitrite in perfusates was more evident and more pronounced with P.O. 085 DV. 6 Reperfusion‐induced arrhythmias were significantly reduced by both compounds to the extent of complete protection afforded by compound P.O. 085 DV. 7 The cardioprotective and antiarrhythmic effects of DFT and P.O. 085 DV are discussed.


International Archives of Allergy and Immunology | 1991

Effect of Nitric Oxide Generators on Ischemia-Reperfusion Injury and Histamine Release in Isolated Perfused Guinea Pig Heart

Emanuela Masini; F. Gambassi; Stefano Bianchi; Laura Mugnai; M. Lupini; A. Pistelli; P. F. Mannaioni

In an ischemia-reperfusion model obtained in isolated perfused guinea pig heart by means of a double ligature of the left anterior descending coronary artery, the reperfusion of the ischemic myocardium leads to a release of lactate dehydrogenase and histamine, related to a decrease in the microdensitometry of cardiac mast cells and to a tissue calcium overload. The perfusion of the heart with L-arginine and with nitric oxide donors significantly reduces the release of histamine, the loss of mast cell metachromasia and calcium overload. These effects were potentiated by superoxide dismutase.


Inflammation Research | 1995

Relaxin enhances the coronary outflow in perfused guinea-pig heart: Correlation with histamine and nitric oxide

M. G. Di Bello; F. Gambassi; Laura Mugnai; M. Lupini; T. Bani Sacchi; Mario Bigazzi; P. F. Mannaioni; Emanuela Masini

Relaxin (Rlx) is a heterodimeric member of the insulin family of protein hormones produced predominantly by the corpus luteum and known for its effects during pregnancy [1]. More recently, Rlx has been reported to have additional physiological functions on the cardiovascular system. In fact, it has been shown that Rlx is a powerful vasodilatory agent [2] and that it is able to decrease blood pressure and to increase heart rate and force of contraction, probably by binding to high affinity Rlx receptors identified in rat heart atria [3]. In this study we investigated whether Rlx influences coronary outflow and, since in our recent experiments on rat mast cells Rlx has been found to stimulate nitric oxide (NO) production, we were prompted to search for NO release from the hearts upon Rlx administration.


International Archives of Allergy and Immunology | 1992

Correlation between nitric oxide synthesis and histamine release in mast cells from spontaneously hypertensive rats : influence of aging

Emanuela Masini; E. Gambassi; M. Lupini; A. Pistelli; P. F. Mannaioni

Isolated perfused hearts and serosal mast cells (MC) of 2- 6- and 18-month-old spontaneously hypertensive rats (SH) were compared to hearts and MC from Wistar-Kyoto (WKY) rats of the same age for their ability to release nitric oxide (NO). The relationship between histamine release and NO production was also investigated. In hearts and MC of 2-, 6- and 18-month-old SH rats, the production of NO is significantly lower than in hearts or MC of WKY rats of the same age. Concomitantly, the spontaneous release of histamine in cardiac perfusates and MC reactivity to various exocytotic stimuli (compound 48/80, calcium ionophore A 23187) is modified by aging and hypertension.


Inflammation Research | 1992

Defibrotide decreases histamine release in a guinea-pig model of myocardial ischemia and reperfusion “in vitro”

M. Lupini; F. Gambassi; Laura Mugnai; Stefano Bianchi; Emanuela Masini; P. F. Mannaioni

It has been shown that defibrotide (DFT), a single stranded polydeoxyribonucleotide obtained from bovine lungs, has significant anti-thrombotic, profibrinolytic properties and stimulates the synthesis of prostacyclin. The present study was designed to evaluate the effects of DFT in the isolated perfused guinea-pig heart submitted to ischemia and reperfusion.The release of histamine and lactate dehydrogenase (LDH) after left anterior descending coronary artery ligation and reopening was measured, and the changes in electrocardiographic parameters and the computer-aided analysis of cardiac mast cell metachromasia were evaluated. DFT (8.4×10−6M) significantly decreased both histamine and LDH release during reperfusion but not in the ischemic phase and attenuated ventricular arrhythmias induced by ischemia-reperfusion, leaving the heart rate unchanged. DFT also reduced the loss of mast cell granule metachromasia and calcium overload consequent to ischemia-reperfusion. Indomethacin (10−6M) reduced the protective effect of DFT.


Inflammation Research | 1993

Histamine release by free radicals: Effect of defibrotide (DFT) and its fraction "P.O. 085 D V"

F. Gambassi; M. Lupini; M. G. Di Bello; Laura Mugnai; Emanuela Masini; P. F. Mannaioni

The effects of defibrotide (DFT) and its fraction P.O. 085 D V on rat serosal mast cell histamine release evoked by free radicals were studied. Free radical production was obtained with: a) metabolic activation of arachidonic acid and cocaine by means of liver microsomes (S-10 mix) from polychlorinated biphenyl mixture (PCB)-treated rats; b) metabolic activation of arachidonic acid by means of prostaglandin-H-synthetase (PHS) and c) human platelet aggregation induced by arachidonic acid. DFT and its fraction reduced histamine release evoked by aggregating human platelets; P.O. 085 D V significantly reduced histamine release evoked by metabolic activation of both cocaine and arachidonic acid in the presence of S-10 mix, while DFT was less active on the cocaine-S 10 mix system and ineffective on the arachidonic acid-S 10 mix system. Both drugs were unable to decrease histamine release induced by metabolic activation of arachidonic acid in the presence of PHS.


Journal of Physiology and Pharmacology | 1994

Generation of nitric oxide from nitrovasodilators modulates the release of histamine from mast cells.

Emanuela Masini; Di Bello Mg; A. Pistelli; Silvia Raspanti; F. Gambassi; Laura Mugnai; M. Lupini; P. F. Mannaioni


Pharmacological Research | 1992

Ischemia-reperfusion injury and histamine release in isolated perfused guinea-pig heart: effects of nitric oxide generators.

F. Gambassi; A. Pistelli; M. G. Di Bello; M. Lupini; P. F. Mannaioni; Emanuela Masini


Pharmacological Research | 1992

Ischemia-reperfusion injury and histamine release in isolated perfused guinea-pig heart : effects of nitric oxide generators : IV meeting of the inter-regional group Abruzzo, Lazio, Molise, Toscana, Umbria of the Italian Society of Pharmacology, Pisa, March 11, 1991

F. Gambassi; A. Pistelli; M. G. Di Bello; M. Lupini; P. F. Mannaioni; Emanuela Masini

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F. Gambassi

University of Florence

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A. Pistelli

University of Florence

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E. Gambassi

University of Florence

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