Search PubMed⌕ Search

Biomedical subjects

E Masini

Publications and source records attributed to E Masini.

At least 55 records · Page 3Linked to original sources
PubMed1997

Relaxin counteracts asthma-like reaction induced by inhaled antigen in sensitized guinea pigs.

In previous studies, the peptide hormone relaxin (RLX) was found to inhibit mast cell secretion and platelet activation. It has been established that the release of mediators from these cells plays a central pathogenic role in allergic asthma. This prompted us to ascertain whether RLX may counteract the respiratory and histopathological abnormalities of the asthma-like reaction to inhaled antigen in sensitized guinea pigs. Guinea pigs were sensitized with ovalbumin and challenged with the same antigen given by aerosol. Some animals received RLX (30 microg/kg BW, twice daily for 4 days) before antigen challenge. Other animals received inactivated RLX in place of authentic RLX. Respiratory abnormalities, such as cough and dyspnea, were analyzed as were light and electron microscopic features of lung specimens. RLX was shown to reduce the severity of respiratory abnormalities, as well as histological alterations, mast cell degranulation, and leukocyte infiltration in sensitized guinea pigs exposed to ovalbumin aerosol. RLX was also found to promote dilation of alveolar blood capillaries and to reduce the thickness of the air-blood barrier. This study provides evidence for an antiasthmatic property of RLX and raises the possibility of new therapeutic strategies for allergic asthma in humans.

Administration, Inhalation↗
PubMed1996

Helicobacter pylori and duodenal ulcer: evidence for a histamine pathways-involving link.

OBJECTIVES: A "gastrin link" has been suggested to explain the statistically relevant association between Helicobacter pylori and duodenal ulcer. Given the well known, although not entirely clarified, relationships between gastrin and histamine, the purpose of this study was to assess whether gastric mucosal histamine pathways and, more specifically, histamine-storing cells are involved in the Helicobacter pylori-duodenal ulcer route. METHODS: Fasting serum gastrin, gastric mucosal histamine content, and mucosal density of both enterochromaffin-like cells and mast cells were compared in 11 H. pylori-positive, non-duodenal ulcer subjects, in 16 duodenal ulcer patients (all H. pylori positive), and in 11 H. pylori-negative control subjects. RESULTS: Fasting serum gastrin concentration and mucosal histamine content were significantly higher in the duodenal ulcer group than in controls, whereas H. pylori-positive, non-ulcer subjects had values that were intermediate between those of the other two groups. Enterochromaffin-like cell density was significantly greater in duodenal ulcer patients than in the other groups. CONCLUSIONS: These results demonstrate the involvement of histamine pathways in H. pylori infection and duodenal ulcer. The most original finding in this study was that enterochromaffin-like cell density is three times greater in duodenal ulcer patients than in H. pylori-positive, non-ulcer subjects. This could explain the previous report of an exaggerated acid response to gastrin in duodenal ulcer patients when compared with H. pylori-positive, non-ulcer subjects and thus provide further insight into the pathogenesis of ulcers.

Biopsy↗
PubMed1995

Relaxin activates the L-arginine-nitric oxide pathway in human breast cancer cells.

Recently, we demonstrated that relaxin (RLX), a peptide hormone of ovarian origin, inhibits growth and promotes differentiation of MCF-7 breast adenocarcinoma cells. We also showed that RLX stimulates the production of nitric oxide (NO) in several cell types. NO has been reported to have antitumor activity by inhibiting proliferation, promoting differentiation, and reducing the metastatic spread of some tumor cell types. In this study, we aimed at evaluating whether RLX influences the L-arginine-NO pathway in MCF-7 cells. The cells were grown in the absence or presence of RLX at different concentrations, and cell proliferation, constitutive and inducible NO synthase activities, nitrite production, and intracellular levels of cyclic GMP were investigated. The results obtained indicate that RLX increases inducible NO synthase activity and potentiates NO production. This was accompanied by an elevation of intracellular cyclic GMP, which is known to mediate the cell response to NO. The RLX-induced activation of the L-arginine-NO pathway in the MCF-7 cells was inversely related to the rate of cell proliferation. These results suggest that the cytostatic effect of RLX on MCF-7 breast cancer cells may rely on its ability to stimulate endogenous production of NO.

Arginine↗
PubMed1995

Gastric mucosal histamine storing cells. Evidence for different roles of mast cells and enterochromaffin-like cells in humans.

Gastric mucosal histamine content, enterochromaffin-like cell density, and mast cell density were studied in 13 subjects under omeprazole therapy, 13 partially gastrectomized subjects with a Billroth II reconstruction, 10 partially gastrectomized subjects with a Roux-en-Y reconstruction, and 9 control subjects. Histamine content was significantly greater both in the subjects with higher gastrinemic levels (omeprazole-treated subjects) and those with more abundant enterogastric reflux (Billroth II subjects) than in controls. Enterochromaffin-like cell density was significantly greater in the omeprazole subjects than in each of the other groups. Mast cell density was significantly greater in Billroth II subjects than in controls. Serum gastrin levels, mucosal histamine content, and enterochromaffin-like cell density were positively correlated. Gastrin was not correlated to mast cell density. These results support the existence of different control pathways for enterochromaffin-like and mast cells. Moreover, they suggest that enterochromaffin-like cells and mast cells are involved in the regulation of gastric secretion and in gastric mucosal injury-repair mechanisms, respectively, due to histamine release.

Aged↗
PubMed1995

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

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 NG-monomethyl-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.

Acetylcholine↗
PubMed1995

Relaxin-induced increased coronary flow through stimulation of nitric oxide production.

1. Relaxin (RLX) is a multifunctional hormone which, besides its role in pregnancy and parturition, has also been shown to influence the cardiovascular system. In this study, we investigated the effect of RLX on coronary flow of rat and guinea-pig hearts, isolated and perfused in a Langendorff apparatus. RLX was either added to the perfusion fluid at a concentration of 5 x 10(-9) M for a 20-min perfusion, or given as a bolus into the aortic cannula at concentrations of 10(-9) M, 5 x 10(-8) M dissolved in 1 ml of perfusion fluid. 2. RLX, given either for a 20-min perfusion or as a bolus in the aortic cannula to guinea-pig and rat isolated hearts, increased the coronary flow and the amount of nitrite, a stable end-product of nitric oxide (NO) metabolism, that appeared in the perfusates in a concentration-dependent fashion. 3. The increase in coronary flow and in nitrite in the perfusates induced by RLX was significantly reduced by pretreatment with the nitric oxide synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA, 10(-4) M). 4. The effects of RLX on coronary flow and nitrite amounts in the perfusates were compared with those induced by the endothelium-dependent vasodilator agent, acetylcholine (ACh, 10(-8)-10(-7) M), and by the endothelium-independent vasodilator agent, sodium nitroprusside (SNP, 10(-7)-10(-6) M). The results obtained show that RLX is more effective than ACh and SNP in increasing coronary flow. 5 The results of this study show that RLX increases coronary flow through stimulation of NO production; hence this hormone should be regarded as a novel agent capable of improving myocardial perfusion.

Acetylcholine↗
PubMed1995

Relaxin depresses platelet aggregation: in vitro studies on isolated human and rabbit platelets.

BACKGROUND: Relaxin, a peptide hormone of ovarian origin, has been shown to cause a striking dilatory action on microvessels in different organs. In our recent studies, relaxin has been shown to stimulate the production of nitric oxide, a powerful vasodilatory agent, in several targets. Nitric oxide also inhibits platelet aggregation. This prompted us to search for a role of relaxin in platelet function. EXPERIMENTAL DESIGN: The effect of relaxin on platelet aggregation was studied in isolated human and rabbit platelets. The samples were incubated with relaxin at different concentrations and then stimulated with collagen or thrombin. Aggregation and intracellular levels of cGMP and Ca2+ were determined. In some experiments, inhibitors or potentiators of nitric oxide activity were also used to clarify whether the mechanism of action of relaxin involves the L-arginine-nitric-oxide pathway. Electron microscopy of platelets treated and not treated with relaxin was also carried out. RESULTS: Preincubation of the platelets with relaxin before stimulation with proaggregants resulted in a significant, concentration-dependent inhibition of platelet aggregation, accompanied by an elevation of intraplatelet cGMP and a decrease in the rise of cytosolic Ca2+ levels. The effect of relaxin appeared to be mediated through nitric oxide. Ultrastructurally, relaxin was shown to hinder the conformational changes and granule exocytosis usually occurring in platelets during aggregation. CONCLUSIONS: This newly recognized antiaggregatory property of relaxin, together with the vasodilatory and hypotensive activities of the peptide demonstrated in previous studies, allows for this hormone to be regarded as a protective agent against thrombotic and hypertensive disorders of pregnancy and cardiovascular diseases.

Adult↗
PubMed1995

Increased production of nitric oxide by neutrophils and monocytes from cirrhotic patients with ascites and hyperdynamic circulation.

An increased release of nitric oxide (NO), a powerful vasodilating agent, has been proposed to play a role in the pathogenesis of vasodilation and hyperdynamic circulation associated with advanced cirrhosis. We evaluated NO synthase (NOS) activity in peripheral leukocytes of 12 cirrhotic patients and 9 healthy subjects together with plasma endotoxin levels and systemic hemodynamic (by a noninvasive echocardiographic method). NOS activity was evaluated by (1) measuring the capacity of isolated polymorphonuclear cells (PMNs) and monocytes to convert [3H]arginine to [3H]citrulline; (2) measuring the ability of neutrophils and monocytes to inhibit thrombin-induced platelet aggregation and to increase guanosine 3'-5'-cyclic monophosphate content in coincubated platelets, an expression of NO release from these cells. Both neutrophils and monocytes from cirrhotic patients produced significantly higher amounts of [3H]citrulline than cells obtained from healthy subjects (P < .001 and P < .02 for neutrophils and monocytes, respectively) and were more effective than control cells in inhibiting platelet aggregation (P < .05 and P < .001, respectively for 2 x 10(6) cells) and in increasing guanosine 3'-5'-cyclic monophosphate content in coincubated platelets (P < .05 and P < .001, respectively). The anti-aggregating activity expressed by leukocytes has a pharmacological profile similar to that described for NO, because it increased after addition of superoxide dismutase, a superoxide anion scavenger, and markedly decreased after inhibition of nitric oxide synthesis with NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine-methyl ester (L-NAME). Cirrhotic patients had significantly higher plasma endotoxin levels (P < .001) and cardiac index (P < .01) when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Nitric oxide modulates cardiac and mast cell anaphylaxis.

Anaphylaxis in the isolated guinea-pig heart was associated with a sudden release of histamine with a long-lasting release of nitrite (NO2-), an oxidation product of NO. NG-monomethyl-L-arginine (MeArg, 300 microM) increased the severity of cardiac anaphylaxis, as shown by the decrease in the coronary flow and by a prolonged duration of antigen-induced arrhythmias. Concomitantly, MeArg increased the release of histamine while decreasing the release of nitrite. Sodium nitroprusside (NaNP, 10(-5)-10(-4) M) reduced the severity of cardiac anaphylaxis by increasing coronary flow and shortening the duration of antigen-induced arrhythmias. Concomitantly, NaNP decreased the release of histamine while increasing the release of nitrite. In mast cells isolated from actively sensitized guinea-pigs, the release of histamine elicited by specific antigen was increased by MeArg and decreased by NaNP. In conclusion, endogenous and exogenous NO antagonizes the effect of vasoconstrictor mediators released after antigen challenge and plays a protective role in anaphylactic reactions "in vitro".

Amino Acid Oxidoreductases↗
PubMed1994

Helicobacter pylori potentiates histamine release from rat serosal mast cells induced by bile acids.

In the present study we have experimentally addressed the effects of Helicobacter pylori on the bile acid capability of histamine release. Bile acids alone were confirmed to be able to induce in vitro histamine release from rat serosal and mucosal mast cells. On the contrary, no significant histamine release was obtained when incubating any Helicobacter pylori preparations alone with mast cells. However, histamine release induced by bile acids was significantly enhanced, without any significant increase in lactate dehydrogenase activity, when whole washed or formalin-killed bacterial cells or crude cell walls were incubated with mast cells in the presence of cholic (0.3 mM), deoxycholic (0.3 mM), or lithocholic (0.3 mM) acids, chenodeoxycholylglycine (0.3 mM), and deoxycholyltaurine (3 mM). The electron microscopic features of mast cells incubated with Helicobacter pylori were consistent with an exocytotic secretion. The release of histamine induced by 0.3 mM deoxycholic acid in the presence of Helicobacter pylori was inhibited by the preincubation of the cells with dimaprit (an H2 agonist) and potentiated by the H2 antagonist, ranitidine. The current results suggest a link between human Helicobacter pylori infection and histamine release and a possible involvement of gastric mucosal mast cells in the pathogenesis of Helicobacter pylori-associated gastritis.

Animals↗