Definition of platelet-derived histamine-releasing factor and histaminergic receptors modulating platelet aggregation.

Endogenous and exogenous free radical scavengers significantly decrease mast cell histamine release induced by coincubation with resting, activated platelets or with platelet-derived supernatant. Histamine and pyridylethylamine dose-dependently enhance platelet aggregation; the effect is potentiated by ranitidine and blocked by mepyramine. Histamine increases also cytosolic calcium concentration in platelets stimulated with thrombin, and binding sites for [3H]-mepyramine are present on platelet membranes.     

Prostaglandin H synthetase activates xenobiotics into free radicals: histamine release and biochemical characteristics

In isolated rat serosal mast cells, studies with the fluorescent Ca2+ indicator, quin 2, and with [3H]-myoinositol to label endogenous polyphosphoinositides have established that an increase in cytosol Ca2+ levels was obligatory for histamine release by free radicals. No substantial breakdown of phosphatidylinositol and related polyphosphoinositides was associated with generation of the Ca2+ signal and histamine release, suggesting that the release of histamine by free radicals entails different pathways than the calcium-mobilizing receptors linked to polyphosphoinositides as second messengers.     

Exercise-induced intravascular haemolysis in standardbred horses

 In human sports medicine a pathophysiological condition called `sports anaemia' is reported. This condition has been attributed to episodes of intravascular haemolysis induced by physical exercise. The occurrence of haemolytic episodes is indicated by the presence of high values of free plasma haemoglobin and lower plasma levels of haptoglobin after physical exercise. The literature regarding sports anaemia in horses, and in particular haemolysis induced by physical exercise, is rather limited. The purpose of this study was to evaluate the markers of intravascular haemolysis (plasma haemoglobin and haptoglobin) in Standardbred horses immediately after a race, in order to ascertain the presence of intravascular haemolysis, possibly induced by physical activity. We reported both the haptoglobin and free plasma haemoglobin values as a percentage of the total protein to avoid any influence of haemoconcentration induced by the exertion during the race. Free plasma haemoglobin concentration showed a significant increase both at 5 min (p < 0.01) and 10 min (p < 0.05) after exercise. A significant decrease in the haptoglobin occurred in both post-exercise blood samples, and was statistically significant 10 min after the race (p < 0.05). These data suggested that episodes of intravascular haemolysis may occur during physical activity in Standardbred horses. Received: 13 May 2002 / Accepted: 15 September 2002 Acknowledgements The authors are very grateful to Dr Lorenzo Berti (Florence, Italy) for his assistance in enrolling the subjects for the study; and to Dr David Marlin (Animal Health Trust, Newmarket, UK) for his advice.     

Helicobacter pylori potentiates histamine release from rat serosal mast cells

We have studied the effect ofHelicobacter pylori (H. pylori) and its bacterial products on mast cell histamine release evoked by compound 48/80, calcium ionophore A 23187 and cholic acid. No significant histamine release is obtained when the various bacterial preparations ofH. pylori are incubated alone with mast cells, but the release of histamine is dose-dependently and significantly enhanced when whole washed and formalin killed cells or crude cell walls are incubated with compound 48/80, calcium ionophore A 23187 or cholic acid. Crude cell walls show the highest activity whereas the filtered supernatants from broth cultures are consistently inactive.The present results indicate a link betweenH. pylori and histamine release and suggest a further involvement of gastric mucosal mast cells in the pathogenesis ofH. pylori-associated gastritis. However, these data need to be extended before any clinical implications can be drawn.     

Mast cells as a source of superoxide anions and nitric oxide-like factor: relevance to histamine release.

Rat serosal mast cells (MCs, 85-90% pure), obtained from peritoneal washing of Wistar albino rats, produced a significant amount of superoxide anions (O2.-) as measured by the increase in absorbance due to the reduction of ferricytochrome c; they were also able to generate a nitric oxide (NO)-like factor, as measured by two bioassay systems: i) inhibition of platelet aggregation and ii) stimulation of MCs guanylate cyclase. Incubation of MCs with human washed platelets resulted in an inhibition of thrombin-induced platelet aggregation which was proportional to cell number. The inhibitory activity of MCs was potentiated by substances which preserve NO (superoxide dismutase, SOD), and reversed by compounds which inactivate NO (oxyhaemoglobin, oxyHb) or which inhibit its synthesis (NG-monomethyl-L-arginine, MeArg). Mechanical stimulation of MCs produced a time-dependent increase in the levels of their cGMP but not cAMP; this increase was enhanced by E. coli lipopolysaccharide (LPS). NO generators such as sodium nitroprusside (NaNp) also augmented the levels of cGMP in MCs. NaNp inhibited in a dose-dependent manner the release of histamine evoked by compound 48/80 (0.5 microgram/ml), but not by the O2.--generating system (xanthine-xanthine oxidase), suggesting a bidirectional regulation of histamine release afforded by O2.- and NO.     

Correlation between cholinergic histamine release and quinuclidinyl-benzilate ([3H]-QNB) binding in mast cell membranes

Isolated purified rat mast cells release histamine when exposed to acetylcholine according to a different pattern of sensitivity. No correlation was found between the release of histamine evoked by acetylcholine and the high affinity binding of [³H]-quinuclidinyl-benzilate (QNB), a specific cholinergic muscarinic ligand, to rat mast cell membranes, since QNB binding was the same in membrane isolated from cells which were sensitive or insensitive to acetylcholine.In murine neoplastic mast cells, a negative correlation was found between histamine release and [³H]-QNB binding, as no evidence of specific [³H]-QNB binding was present in murine neoplastic mast cell membranes which, accordingly, do not release histamine when exposed to acetylcholine.It is concluded that murine neoplastic mast cells are not provided with muscarinic cholinergic receptors. In rat mast cells, muscarinic cholinergic receptors are always present, but not always coupled with the effector mechanisms triggering the exocytosis.     

Influence of aging on mast cell production of a nitric oxide-like factor: Comparison between normal and hypertensive rats

Rat serosal mast cells (MCs) isolated from Wistar albino rats synthesize a nitric oxide (NO)-like factor which inhibits platelet aggregation, stimulates guanylate cyclase and modulates mast cell histamine release. Aging can affect the ability of MCs to generate and release chemical mediators.

The aim of the present study was to evaluate the ability to generate a NO-like factor by MCs isolated from 2, 6 and 18 month old normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats (systolic blood pressure 180±2.5 mm Hg) by two bioassays: inhibition of platelet aggregation and stimulation of MC guanylate cyclase.

MCs from SH rats produced less NO-like activity than MCs from normotensive WKY rats of the same age. In both strains aging decreased the capacity of MCs to generate the NO-like factor. These results suggest that NO synthesis and/or release from MCs is involved in some events associated with aging and hypertension.

     

Biological markers and therapeutic outcome in alcoholic disease: A twelve-year survey

Summary The early diagnosis and evaluation of the biological consequences of alcohol abuse are reviewed in a population of 401 chronic alcoholics admitted to our Toxicological Unit from January 1973 to the end of December 1984; selected cases were treated with disulfiram implantation. The results of the study indicate that anemia with increased globular volume of erythrocytes, elevated serum -glutamyl-transferase activity, increased postprandial cholalemia, and increased elimination of pentane in the breath can be considered suitable markers for the early diagnosis of alcohol abuse. Disulfiram implantation significantly prolonged the abstinence duration in the treated patients.Abbreviations ADH Alcohol dehydrogenase - ALDH Aldehyde dehydrogenase - DER Disulfiram-ethanol reaction - SGOT Serum glutamic oxalacetic transaminase - SGPT Serum glutamic pyruvic transaminase     

Mast cell and neutrophil interactions: A role for superoxide anion and histamine

Histamine inhibits superoxide anion (O ₂ ^– ) production from human neutrophils stimulated by N-formylmethionlyleucyl-phenylalanine (FMLP). The effects of histamine are dose-dependent and competitively antagonized by cimetidine. When passively sensitized rat serosal mast cells and human neutrophils are mixed together, O ₂ ^– production from FMLP-activated granulocytes is significantly reduced, following mast cell degranulation by acetylcholine. These inhibitory effects can be counteracted by cimetidine. Exposure of non-sensitized rat mast cells to FMLP-stimulated human neutrophils causes histamine release. These results suggest bidirectional control mechanisms between mast cells and neutrophils, that further stress the role of histamine in regulating inflammatory processes.     

Ischemia-reperfusion injury and histamine release in isolated guinea-pig heart: The role of free radicals

Free radicals produced by the occlusion and opening of the left anterior descending coronary artery and/or by perfusion of isolated guinea-pig heart with FeCl₃/ADP (10 M/100 M) induce a differential release of histamine and lactate dehydrogenase (LDH) in the perfusates with a preferential liberation of histamine in the reperfusion phase, associated with an increase of ventricular arrhythmias. The release of histamine has been correlated with malonyldialdehyde (MDA) production and tissue calcium content in left ventricular tissue. MDA increased during ischemia, while the calcium content increased when the tissue was reperfused. Under these conditions, N-t-butyl--phenylnitrone (BPN), a molecule capable of forming spin adducts with free radicals, andd-mannitol are active in preventing reperfusion-induced arrhythmias.