Minute amounts of histamine and a discrete histamine-forming capacity was present in quiescent human platelets. Aggregation of human platelets induced by thrombin was concomitant with the release of histamine. in platelets obtained from actively sensitized guinea pig, the exposure to the specific antigen results in aggregation and histamine release, which was not reproduced by the exposure to an unspecific protein or in platelets taken from unsensitized animals. The present results lend further support to positioning platelets among the inflammatory cells.

We report on the effectiveness and safety of gamma-hydroxybutyric acid in the therapy of overt alcohol withdrawal syndromes, their prevention, and the prevention of relapses in formerly detoxified alcoholics. We studied 321 patients (236 men, 85 women), divided into two open-study groups for the treatment and prevention of alcohol withdrawal syndromes and one double-blind study group to evaluate the effects of gamma-hydroxybutyric acid versus placebo on alcoholic craving and relapses in detoxified patients. Gamma-hydroxybutyric acid treatment promptly reduced withdrawal symptoms in all patients and prevented alcohol withdrawal syndromes in 55% of cases. The attenuation of craving in detoxified patients was significantly greater in the gamma-hydroxybutyric acid-treated group in comparison with the placebo-treated group. The therapeutic use of gamma-hydroxybutyric acid was not accompanied by serious side effects. Gamma-hydroxybutyric acid diversion was poorly represented: gamma-hydroxybutyric acid-induced abuse was reported in 4 (1.1%) of 345 treated patients, and only 9 cases of gamma-hydroxybutyric acid acute poisoning were reported in the years 1992–1995. Our results suggest that gamma-hydroxybutyric acid, with a favorable risk/benefit ratio, is a clinically useful drug in the treatment of alcohol dependence.

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.

Anaphylaxis in the isolated guinea-pig heart was associated with a sudden release of histamine with a long-lasting release of nitrite (NO 2 − ), an oxidation product of NO.NG-monomethyl-l-arginine (MeArg, 300 μM) 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, 10−5–10−4M) 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.

Aggregation of human platelets induced by thrombin was concomitant with the release of histamine. In platelets obtained from actively sensitised guinea-pigs, the exposure to the specific antigen results in aggregation and histamine release which was not reproduced by exposure to an unspecific protein, or in platelets taken from unsensitised animals.

The influence of histamine on human platelet function was studied by measuring the uptake of [3H]-histamine and by evaluating the effect of histamine on Ca2+ influx and on intracellular Ca2+ levels. The uptake of histamine by platelets is significantly reduced by mepyramine and unaffected by cimetidine. Histamine was found to increase both the [45Ca]2+ uptake by resting and stimulated platelets, and the intracellular Ca2+ levels in Fura 2-AM loaded platelets. H1-antihistaminics significantly reduced these processes, suggesting a role for histamine, which in platelets promotes aggregation by acting through H1-receptors modulating intracellular Ca2+ levels.

The effects of reduced glutathione (GSH) administration (1.2 g/day and 2.4 g/day intravenously) on erythrocyte glutathione levels, serum gamma-glutamyl transpeptidase activity (GGTP) and urinary glucaric acid elimination were studied in a population of 24 chronic alcoholics voluntarily admitted to a 30 day detoxification protocol in comparison to a 12 patient control group treated only with chlordiazepoxide (initial dose 75-100 mg/day). Glutathione treatment increases dose-dependently and in a significant way erythrocyte glutathione levels and hastens the recovery of serum GGTP and urinary glucaric acid elimination. The relationship between glutathione, GGTP and glucaric acid is discussed, suggesting the possible role of GSH against the oxidative damage of alcohol.