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Biomedical subjects

L Mugnai

Publications and source records attributed to L Mugnai.

18 recordsLinked to original sources

Chemical structure of two phytotoxic exopolysaccharides produced by Phomopsis foeniculi.

The two main exocellular polysaccharides produced in vitro by Phomopsis foeniculi, a fungal pathogen of fennel, were isolated and characterized by chemical and spectroscopic methods as a galactan with the known structure [-->6)-beta-D-Galf-(1-->5)-beta-D- Galf-(1-->5)-beta-D-Galf-(1-->]n and a mannan. The latter consists of a backbone of alpha-(1-->6)-linked mannopyranose units. Almost all of these are branched at the 2 position with arms containing 2- and 3-linked mannopyranose units. The crude polysaccharide fraction and its components, galactan and mannan, showed phytotoxic effects, i.e. chlorosis, necrosis and/or wilting, on fennel and on two non-host plants, tobacco and tomato.

Ascomycota↗

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↗

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↗

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↗

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

The effect of organic and inorganic nitrovasodilators (sodium nitroprusside; 3-morpholinosydnonimine; glyceryl trinitrate; isosorbide dinitrate; sodium nitrite, was studied on the release of histamine evoked by compound 48/80 and calcium ionophore A 23187 in isolated purified rat serosal mast cells. All the compounds tested were capable of significantly reducing the release of histamine in a concentration-dependent fashion, at different levels of potency. This effect was reverted by oxyhaemoglobin. The inhibitory effect of glyceryl trinitrate on the release of histamine was potentiated in cells taken from animals pretreated with Escherichia coli lipopolysaccharide, and decreased by NG-nitro-L-arginine methyl ester. Glyceryl trinitrate and isosorbide dinitrate concentration-dependently increase the generation of nitric oxide by rat serosal mast cells. The inhibitory effect of glyceryl trinitrate and isosorbide dinitrate on the release of histamine from mast cells was potentiated by N-acetylcysteine, which significantly increases the generation of nitric oxide by mast cells. It is concluded that nitrovasodilators inhibit the release of mast cell histamine through the generation of nitric oxide. The effect may be relevant in considering the perivascular location of mast cells and the role played by these cells in cardiovascular pathophysiology.

Acetylcysteine↗

Reflux-related gastric mucosal injury is associated with increased mucosal histamine content in humans.

BACKGROUND: Experimental studies in the dog and the rat have shown histamine involvement in reflux-related gastric mucosal injury. However, no definite demonstrations of a link between reflux-related gastric mucosal injury and mast cell mediators exist in humans. METHODS: The relationships between reflux, gastric mucosal histamine content, and gastric histology were assessed in partially gastrectomized subjects presumptively with high (11 Billroth II subjects) and low reflux levels (9 total biliary diversion subjects), respectively. Findings were compared with those in a control group consisting of 8 endoscopically and histologically proven normal subjects. RESULTS: Bile acid quantity and concentration in the gastric aspirates were significantly greater in Billroth II subjects than in total biliary diversion subjects. Significantly higher cumulative scores for foveolar hyperplasia, mucosal edema, capillary dilatation and congestion, and smooth muscle fibers in the lamina propria were found in Billroth II subjects than in total biliary diversion subjects. Mucosal histamine content as well as mast cell density and degranulation differed significantly between Billroth II and the other two groups. CONCLUSIONS: These results represent the first demonstration in humans of an association between mast cell mediators and chemical gastric mucosal injury.

Adult↗

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

Experiments were carried out to provide evidence of the effect of L-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.

Animals↗

Effects of nucleus basolateralis amygdalae neurotoxic lesions on aversive conditioning in the rat.

After bilateral stereotaxic administration of ibotenic acid on the n. basolateralis amygdalae, male adult rats were tested in the light-dark box apparatus to measure the time-course of the acquisition and retention of passive and active avoidance responses. The results show that after the lesions both passive avoidance and active avoidance acquisition were impaired. Passive avoidance responses were retained quite well, while active avoidance responses disappeared quickly. Conditioned freezing was almost completely absent. Thus it appears that the n. basolateralis plays a facilitatory role in all the conditioned responses which were investigated.

Amygdala↗

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

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.

Animals↗

Mast cell fixation and staining in image analysis.

Modern image analysers automatically perform densitometric measurements and elaborate digital images. Elaboration however is subject to operator interpretation and often eliminates precious information from the areas of interest. For this reason, it was appropriate to find a staining method which would overcome this drawback and, in the case of mast cell histochemistry, limit staining to granule content. The following current staining techniques were tested: Toluidine Blue in buffered solution (solut. a) and in 0.003% alcoholic solution (solut. b) and alcoholic Astra Blue, pH 0.2 Densitometric analysis was performed on both 5 microns and semithin sections of mouse tongue fixed in Isotonic formaldehyde-acetic acid (IFAA). Digital images were obtained using 630 nm and 546 nm wavelengths for Toluidine Blue and 610 nm for Astra Blue. Direct comparison between the two Toluidine Blue solutions revealed that more pixels were captured by the 5 microns sections stained with solut. a, whilst the opposite occurred in semithin sections. Both dyes introduced a certain amount of error due to the orthochromatic component of the nucleus and cytoplasmic basophily, which had to be eliminated through image elaboration. Because of its subjective nature, this operation may in turn lead to further errors. The choice of Astra Blue as an alternative to Toluidine Blue in densitometric analysis of mastocytes is based on its property to restrict staining to the granules of mast cells. A comparison between Astra Blue and the two Toluidine Blue solutions showed that, at all transmission levels, preparations stained with Astra Blue captured more pixels than those stained with Toluidine Blue. Consequently our results suggest that the most suitable technique for densitometric image analysis is fixation of mast cells in IFAA followed with Astra Blue.

Animals↗

Isolation and characterisation of a new antagonistic Burkholderia strain from the rhizosphere of healthy tomato plants.

A new Burkholderia strain (PVFi5A) which exhibits antagonism towards many bacterial and fungal plant pathogens has been partially characterised. This strain was isolated from the rhizosphere of tomato plants and was referred to the Burkholderia cepacia complex on the basis of cultural, morphological and biochemical characteristics, including determination of the 16S ribosomal DNA sequence and fatty acid profile. Strain PVFi5A is a Gram-negative, aerobic bacterium, oxidase- and catalase-positive, motile with a polar tuft of flagella, able to grow on a variety of media without producing diffusible pigments; it is avirulent to onion, able to grow at 41 degrees C and resistant to several antibiotic substances. Its fatty acid profile contains the hydroxy acids 18:1 20H, 14:0 3OH and 16:0 3OH, but not the hydroxy acids 16:0 2OH. The antagonistic activity of strain PVFi5A is due to its production of various, as yet unidentified, antimicrobial compounds, one or more of which may differ from those reported previously for certain 'B. cepacia' strains. The ability of PVFi5A to suppress the growth of important bacterial and fungal phytopathogens makes this strain a potential biocontrol agent.

Anti-Bacterial Agents↗

Changes in the production of nitric oxide and superoxide by inflammatory cells in liver cirrhosis.

Superoxide (O2-) and nitric oxide (NO) production by polymorphonuclear leukocyte (PMNs) and monocytes in patients with liver cirrhosis were evaluated. PMNs obtained from cirrhotic patients were less effective than those from controls in producing O2- after stimulation with opsonized zymosan, while they were more effective in producing NO, as shown by the inhibition of platelet aggregation and by the increase in cGMP content. NO synthase activity was higher in leukocytes from cirrhotic patients than in controls. A correlation was found between the cardiac index and the observed changes in the inflammatory cells.

Arginine↗

[Acidosis, hypoxia and hypotension in abdominal chemotherapy with blockade of arterial and venous circulation (stop flow)].

BACKGROUND AND AIM: A study was performed of the perioperative systemic effects of a recent zoned chemotherapy technique administered in conditions of extreme acidosis, hypoxia and modern hypotension. METHODS EXPERIMENTAL DESIGN: a prospective analysis of the changes compared to basal values using Student's t test for paired data. SETTING: Operating theatres and Recovery room. PATIENTS OR PARTICIPANTS: A population of 16 consenting patients suffering from abdominal or pelvic neoplasms, ASA 1-3, recruited according to the parameters suggested by the international literature. SURGERY: central venous catheter, radial arterial catheter, open catheter of the e.v. femoral artery, general anesthesia using isoflurane. Tests performed: Blood gas analysis of systemic arteries, abdominal veins and the superior vena cava at times preceding clamping (T0) and 7 and 14 mins after the start, at declamping, on reawakening from anesthesia and 30 and 60 mins afterwards (T1, T2, T3, T4, T5, T6). Serial evaluation of activated coagulation time. RESULTS: Mean 25% reduction of neoplastic mass, systemic arterial and venous pH diminished at T1 and T2, but more marked and transient at T3; district venous pH significantly diminished during entire Stop-Flow. Systemic PaO2 increased throughout method (SaO2 > 98%). PaO2 in the superior vena cava recorded significantly higher intraoperative values compared to basal and postoperative levels, no major differences found at time T3. SaO2 showed statistically significant differences between the superior vena cava and the abdominal distrist at both T 1 (p 0.0002) and T2 (p 0.004). No toxic effects due to NPS were observed. CONCLUSIONS: This is a safe technique but not without risks, which requires considerable anesthesiological commitment.

Abdominal Neoplasms↗