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Biomedical subjects

E Masini

Publications and source records attributed to E Masini.

At least 19 recordsLinked to original sources
PubMed2006

A topical nitric oxide-releasing dexamethasone derivative: effects on intraocular pressure and ocular haemodynamics in a rabbit glaucoma model.

BACKGROUND: Topical nitric oxide-releasing dexamethasone (NCX1021) may avoid the negative effects of dexamethasone phosphate. AIMS: To obtain more information on the role of nitric oxide in glaucoma and to compare a nitric oxide-releasing dexamethasone with dexamethasone phosphate with regard to intraocular pressure (IOP) and ocular haemodynamics in an experimental rabbit model. METHODS: Six rabbits were treated with dexamethasone phosphate 0.1% in the right eye and with NCX1021 in the left eye for 5 weeks. The parameters considered were IOP, nitric oxide marker levels in aqueous humour, ocular haemodynamics of ophthalmic artery (by means of colour Doppler imaging), expression of endothelial nitric oxide synthase (eNOS)in ciliary processes and histology of ciliary bodies. RESULTS: Dexamethasone increased IOP levels, NCX1021 did not. Nitrite and cyclic guanosine monophosphate levels in aqueous humour were lowered by dexamethasone and increased by NCX1021. Resistivity index of the ophthalmic artery was increased, eNOS expression was reduced and ciliary bodies showed histological lesions in dexamethasone-treated eyes, not in NCX1021-treated ones. CONCLUSIONS: NCX1021 may avoid the IOP increase, impairment of ocular blood flow and the morphological changes in the ciliary bodies possibly induced by corticosteroid treatment.

Animals↗
PubMed2006

Carbon monoxide: the bad and the good side of the coin, from neuronal death to anti-inflammatory activity.

The double origin of carbon monoxide (CO) as an atmospheric pollutant or as an endogenous gaseous modulator of many pathophysiological processes prompted us to review some aspects of the bad side and of the good side of coin among the pleiotropic effects of CO. On the bad side of the coin, we focus on the interval form in acute CO poisoning, discussing experimental evidence suggesting that the delayed neuropathology after CO poisoning is a free radical-driven event. In this context, we challenge the mandatory place of hyperbaric oxygen therapy (HBO) in CO poisoning as a possible summation of oxy-radicals generated by HBO and the free radical cascade set in motion during the reoxygenation phase of acute CO-poisoning. We also discuss an opposing view, which provides evidence suggesting that HBO therapy actually decreases the load of free radicals in acute CO-poisoning and may be beneficial in preventing delayed neuropsychiatric sequelae.On the good side of the coin, we briefly outline the endogenous generation of CO and the leading role of heme-oxygenases (HO) in relation to the place of CO in biology and medicine. The main focus of this section is on the growing literature on CO and inflammation. Here we report on in-vitro and in-vivo studies on the modulation afforded by exogenously administered/endogenously produced CO in a variety of experimental and clinical settings of inflammation. Our recent studies on experimental models of allergic inflammation are also discussed, and the CO-releasing molecules envisaged as potential anti-inflammatory drugs suitable for clinical use.

Animals↗
PubMed2005

Protection from cardiac injury by induction of heme oxygenase-1 and nitric oxide synthase in a focal ischaemia-reperfusion model.

The enzymes heme oxygenase (HO) generate carbon monoxide (CO) in living organisms during heme degradation. Carbon monoxide has recently been shown to dilate blood vessels and to possess anti-inflammatory properties. It is also known that nitric oxide (NO) donors ameliorate cardiac ischaemia-reperfusion injury in experimental models of global or focal ischaemia-reperfusion (FIR). The two gaseous mediators share the same mechanism of action via the stimulation of soluble guanylyl cyclase and the increase in cellular levels of cyclic GMP. We studied the effects of manipulating the HO system and the possible interaction between CO and NO in an experimental in vivo model of FIR in the rat heart. FIR-subjected rats had necrotic area in the left ventricle, ventricular arrhythmias and a shortening of survival time in comparison to sham-operated animals. Resident mast cells underwent a heavy degranulation, malonyldialdehyde was produced by myocardial cell membranes, and tissue calcium levels were increased. High levels of myeloperoxidase were also detected, suggesting a FIR-related inflammatory process. In animals pre-treated with the HO-1 inducer, hemin, all the biochemical and morphometric markers of FIR were minimized or fully abated. Consistently, the biochemical and morphometric markers of FIR were reversed in rats treated with the HO-1 blocker, ZnPP-IX, prior to hemin administration. Pre-treatment with hemin significantly increases the expression and activity of both cardiac HO-1 and iNOS, suggesting that CO and NO cooperate in the cardioprotective effect against FIR-induced damage, and that there is a therapeutic synergism between NO-donors and CO-releasing molecules, via the common stimulation of increase in cGMP levels and decrease in calcium overload.

Animals↗
PubMed2004

Nitric oxide proxies and ocular perfusion pressure in primary open angle glaucoma.

BACKGROUND: To investigate the levels of nitric oxide (NO) markers in plasma and aqueous humour of patients with primary open angle glaucoma (POAG) and their relation to ocular perfusion pressure. METHODS: Cyclic guanosine monophosphate (cGMP) and nitrite (NO(2)(-)) were determined in plasma and aqueous humour of 38 patients with POAG and 46 controls. Blood pressure and IOP were measured to calculate ocular perfusion pressure (PP). RESULTS: cGMP and NO(2)(-) plasma levels were significantly decreased in glaucoma patients compared with controls (p = 0.001 v p = 0.004). In the aqueous humour of subjects with POAG, cGMP and NO(2)(-) concentrations were also lower than in normal eyes (p = 0.0001 v p = 0.001). There was a linear association between cGMP in plasma and aqueous humour in glaucomas and controls (r = 0.514, p = 0.029 and r = 0.558, p = 0.004) and this relation differed in the two groups (p = 0.003). Considering glaucoma patients with controls, a positive correlation was found between cGMP and PP (r = 0.379, p = 0.01) and between NO(2)(-) and PP (r = 0.339, p = 0.040). The cGMP/PP correlation was of borderline statistical significance in controls (p = 0.050), whereas it did not attain statistical significance in POAG, as well as the association between NO(2)(-) and PP when glaucomas and controls were considered separately. CONCLUSIONS: The authors found alterations of NO markers in the plasma and aqueous humour of glaucoma patients. Primary or secondary impaired NO balance could alter ocular perfusion pressure.

Aged↗
PubMed2003

Histaminergic receptors modulate the coronary vascular response in isolated guinea pig hearts. Role of nitric oxide.

OBJECTIVE: The effects of histamine and of histamine receptor agonists and antagonists on the coronary outflow and on the generation of nitric oxide (NO) were evaluated on isolated guinea pig hearts. METHODS: Isolated guinea pig hearts were perfused for 50 min in a Langendorff apparatus with histamine (10(-7)- 10(-8) M), in the absence or in the presence of N(G)-monomethyl-L-arginine (L-NMMA, 10(-4) M), a NO synthase inhibitor and of triprolidine (3.10(-8) M) and cimetidine (10(-7) M), H(1) receptor and H(2) receptor antagonists, and with trifluoromethyl-phenylhistamine (TFMPH, 10(-7) M) and dimaprit (10(-7) M), H(1) and H(2) receptor agonists. The effects of (R)-alpha-methylhistamine (10(-7) M), a H(3) receptor agonist and of FUB 181 (10(-7) M), a H(3) receptor antagonist, were studied in the presence of bradykinin (10(-7) M). RESULTS: Histamine increases the coronary outflow and the generation of NO in a concentration-dependent fashion. The effects were completely abolished by blocking NO-synthase (NOS) with L-NMMA (10 (-4 ) M). The effects were also abolished by cimetidine (10 (-7 ) M), H (2 ) receptor antagonist, and only scarcely affected by triprolidine (3.10 (-8 ) M), H (1 ) receptor antagonist. The effects were reproduced by dimaprit (10 (-7 ) M), H (2 ) receptor agonist, and only scarcely by TFMPH (10 (-7 ) M), a selective H (1 ) receptor agonist. Bradykinin (10 (-7 ) M) produces a sustained coronary dilation paralleled by a marked increase in the generation of NO; the effects were significantly reduced by L-NMMA. The stimulation of H (3 ) receptors by (R)-alpha-methylhistamine (10 (-7 ) M) significantly reduced both effects, which reverted to normal with FUB 181 (10 (-7 ) M), an H (3 ) receptor antagonist. CONCLUSION: These results suggest that, in isolated guinea pig hearts, histamine produces coronary dilation through an H (2 )/H (3 )-dependent mechanism involving the generation of nitric oxide.

Animals↗
PubMed2003

Some new functions of amine oxidases.

Two contrasting topics are examined in this account: the protective actions of amine oxidases (AOs) resulting from the elimination and/or modulation of the levels of polyamines and some biogenic amines, such as histamine, in anaphylactic shock and the cell damaging effect of AOs catabolic products. Other functions of the plasma copper-containing amine oxidase are considered; namely the modification of some proteins by oxidation of their free amino groups, the auto-regulation of the catalytic activity of AOs, the protective effect against free radicals, and the regulation of K(+)-channels.

Journal Article↗
PubMed2002

Differential effects of amphotericin B and liposomal amphotericin B on inflammatory cells in vitro.

OBJECTIVE AND DESIGN: To understand whether the pseudo-allergic reactions to amphotericin B (AmB) administration are due to AmB or to the solubilizing vehicles, a study was designed to evaluate the effects of AmB, liposomal AmB, (L-AmB), AmB-deoxycholate micellar complex (AmB-DC) and deoxycholate (DC) on the responses of rat serosal mast cells (RSMC) and of human basophils (HB), in vitro. MATERIALS AND METHODS: Serosal mast cells were obtained by density gradient centrifugations from male Wistar albino rats. Partially purified HB were obtained from healthy donors. The cells were exposed to AmB, L-AmB, AmB-DC and DC. Histamine release was measured fluorometrically, and the release of lactic dehydrogenase (LDH) was measured spectrophotometrically. HB activation was evaluated cytofluorimetrically by CD63 expression. RESULTS: AmB and L-AmB did not evoke histamine or LDH release from either RSMC or HB. CD63 expression was not induced in HB challenged with AmB and L-AMB. On the other hand, AmB-DC and DC produced a cytotoxic histamine release from both RSMC and HB, and a sustained increase of CD63 expression on HB. CONCLUSIONS: Only AmB-DC was able to induce the release of inflammatory mediators from RSMC and HB. Conceivably, the cytotoxic effect is accounted for by the micellar complexes with DC, which has been confirmed as a powerful histamine releaser, and held responsible for the pseudo-allergic reactions after AmB-DC administration. The data lend support to a better safety profile of L-AmB.

Amphotericin B↗
PubMed2002

Protective effect of relaxin in cardiac anaphylaxis: involvement of the nitric oxide pathway.

1 Relaxin (RLX) is a multifunctional hormone best known for its role in pregnancy and parturition, that has been also shown to influence coronary perfusion and mast cell activation through the generation of endogenous nitric oxide (NO). In this study we report on the effects of RLX on the biochemical and mechanical changes of ex vivo perfused hearts isolated from ovalbumin-sensitized guinea-pigs induced by challenge with the specific antigen. The possible involvement of NO in the RLX action has been also investigated. 2 A 30-min perfusion with RLX (30 ng ml(-1)) before ovalbumin challenge fully abated the positive chronotropic and inotropic effects evoked by anaphylactic reaction to the antigen. RLX also blunted the short-term coronary constriction following to antigen challenge. Conversely, perfusion with chemically inactivated RLX had no effect. 3 The release of histamine in the perfusate and the accumulation of calcium in heart tissue induced by antigen challenge were significantly decreased by RLX, while the amounts of nitrites in the perfusate were significantly increased, as were NO synthase activity and expression and cGMP levels in heart tissue. 4 These findings indicate that RLX has a protective effect in cardiac anaphylaxis which involves an up-regulation of the NO biosynthetic pathway.

Anaphylaxis↗
PubMed2001

Haeme oxygenase-1 and cardiac anaphylaxis.

1. Haeme oxygenase (HO) is an enzyme mainly localized in the smooth endoplasmic reticulum and involved in haeme degradation and in the generation of carbon monoxide (CO). Here we investigate (1) whether the inducible isoform of HO (HO-1) is expressed in the isolated heart of the guinea-pig and (2) the functional significance of HO-1 on the response to antigen in isolated hearts taken from actively sensitized guinea-pigs. 2. Both the HO-1 expression and activity are consistently increased in hearts from guinea-pigs pretreated with hemin, an HO-1 inducer (4 mg kg(-1) i.p., 18 h before antigen challenge). The administration of the HO-1 inhibitor zinc-protoporphyrin IX (ZnPP-IX, 50 micromol kg(-1), i.p., 6 h before hemin) abolished the increase of both the HO-1 expression and activity. 3. In vitro challenge with the specific antigen of hearts from actively sensitized animals evokes a positive inotropic and chronotropic effect, a coronary constriction followed by dilation and an increase in the amount of histamine in the perfusates. In hearts from hemin-pretreated animals, antigen challenge did not modify the heart rate and the force of contraction; the coronary outflow was significantly increased and a diminution of the release of histamine was observed. The patterns of cardiac anaphylaxis were fully restored in hearts from animals treated with ZnPP-IX 6 h before hemin. 4. In isolated hearts perfused with a Tyrode solution gassed with 100% CO for 5 min and successively reoxygenated, the response to antigen was similar to that observed in hearts from hemin-pretreated animals. 5. Pretreatment with hemin or the exposure to exogenous CO were linked to an increase in cardiac cyclic GMP levels and to a decrease of tissue Ca(2+) levels. 6. The study demonstrates that overexpression of HO-1 inhibits cardiac anaphylaxis through the generation of CO which, in turn, decreases the release of histamine through a cyclic GMP- and Ca(2+)-dependent mechanism.

Anaphylaxis↗
PubMed2001

Up-regulation of cyclooxygenase 2 gene expression correlates with tumor angiogenesis in human colorectal cancer.

BACKGROUND & AIMS: Recent studies have shown that cyclooxygenase (COX)-2 and its products, prostaglandins (PGs), may be involved in colorectal carcinogenesis. The aim of this study was to determine whether COX-2 expression and PGE(2) production correlate with microvessel density, vascular endothelial growth factor (VEGF) expression, and tumor metastasis in human colorectal cancer. METHODS: Tumor samples and adjacent normal mucosa were obtained from 31 surgical specimens. Immunohistochemical expression of COX-2, VEGF, and CD31 was analyzed on paraffin-embedded tissue sections. COX-2 and COX-1 proteins were determined by Western blot analysis. COX-2 and VEGF messenger RNA expressions were evaluated using Northern blot analysis. PGE(2) production was determined by specific radioimmunoassay. RESULTS: The immunohistochemical expressions of both COX-2 and VEGF were significantly correlated with microvessel density (P = 0.02 and P = 0.002, respectively). A significant correlation was found between COX-2 and VEGF expression (P = 0.004). Western analysis confirmed the up-regulation of COX-2 protein expression. COX-2 and VEGF genes were overexpressed in tumor specimens as compared with normal mucosa. PGE(2) levels were significantly higher in metastatic tumors than in nonmetastatic ones (P = 0.03). CONCLUSIONS: COX-2 is related to tumor angiogenesis in colorectal cancer. It is likely that VEGF is one of the most important mediators of the COX-2 angiogenic pathway.

Adenocarcinoma↗