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BACKGROUND: Platelets participate in allergic and inflammatory processes beside their role in haemostasis and thrombosis. This paper reports the level, the uptake, the metabolism and the release of histamine in human platelets. The effects of exogenous histamine, as well as the receptor and signal transduction of these effects, are also described. METHODS: Purified suspensions of platelets, prepared from healthy volunteers and from atopic patients, were exposed in vitro to physiological and immunological stimuli. Platelet aggregation was measured by the increase in light transmission; histamine content and release, as well as cytosolic free Ca2+ concentration, were measured fluorimetrically. Platelet histamine forming capacity, and the uptake of exogenous histamine, were measured with a radioisotopic method. RESULTS: Human platelets contain 72.5 +/- 9.6pmoles of histamine x 10(9) platelets, and their capacity to form histamine is 18.7 +/- 3.5pmoles h(-1)g(-1) protein, which is reduced by alpha-fluoromethylhistidine (10(-5) M) a selective inhibitor of the specific histidine decarboxylase. Human platelets take up the preformed amine by a calcium and energy-dependent process, and the uptake of histamine is reduced by mepyramine, an H1-receptor antagonist, and N,N-diethyl-2-[4-(phenylmethyl) phenoxyl] ethanamine (10(-6) M), a blocker of intracellular histamine receptors. Histamine is also metabolized by human platelets. The exposure of platelets to thrombin (10-60 mUml(-1)) produced a progressive aggregation, associated with histamine release. The same is observed in platelets isolated from atopic patients exposed to anti-IgE antibodies. Exogenous histamine dose-dependently potentiates the aggregation induced by physiological and immunological stimuli. In resting platelets cytosolic calcium level (207 +/- 4.2 nM/10(8) platelets) is increased by thrombin as well as by anti-IgE; this effect is potentiated by 10(-5) M histamine. CONCLUSIONS: The synergistic effect between histamine and other monoamines on platelet aggregation may explain some aspects of allergic vasculitis in which platelet aggregation is present.

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BACKGROUND: The metabolic activation of morphine, cocaine and methadone into free radicals could have pathophysiological relevance in the organic injuries of drug addiction. METHODS: Isolated purified rat serosal mast cells were incubated with morphine, cocaine and methadone (10(-7) M-10(-4) M) with oxidative enzymes (prostaglandin-H-synthetase, 25 mU; rat liver homogenate fraction S 10-mix, 400 microl), and with the drugs of abuse in the presence of oxidative enzymes. Histamine and lactate dehydrogenase (LDH) were analysed with a fluorimetric and spectrophotometric assay, respectively; the generation of malonyldialdehyde (MDA) was measured by a spectrophotometric assay. RESULTS: The release of mast cell histamine and the generation of MDA are present only when mast cells were incubated with the drugs of abuse in the presence of oxidative enzymes. This release was dependent on the concentration of the drug in question and showed a maximum value at 10(-4) M. Moreover, in parallel experiments we demonstrated that, under the same experimental conditions, the release of LDH was always less than 20% of the total, suggesting that this effect is due to a selective exocytotic process. Histamine release and MDA generation were abated by the free radical scavengers: reduced glutathione, 10(-4) M GSH and alpha-tocopherol, 10(-4) M and by the spin trapper 5.5-dimethyl-1-pyrroline-N-oxide, 10(-4) M DMPO. The light and electron microscopic features are consistent with exocytotic secretion in the cases of morphine and methadone and with cell lysis in the case of cocaine. CONCLUSION: These results suggest that morphine, cocaine and methadone are activated into free radicals which produce membrane lipid perturbation and histamine release, suggesting that a massive release of mast cell histamine could be an additional risk factor in heroin and cocaine overdoses.

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BACKGROUND: Histamine and nitric oxide (NO) are present in guinea pig hearts and in rat mast cells (MCs) of the serosal phenotype. Histamine and NO are simultaneously released upon immunological challenge of isolated hearts of actively sensitised guinea pigs. MCs release histamine in response to antigen and NO in response to stirring. This has prompted us to study the interaction between histamine and NO in rat MCs and in guinea pig hearts. METHODS: The experiments have been carried out in isolated purified rat serosal MCs and in isolated perfused guinea pig hearts. The generation of NO by both preparations has been evaluated as nitrites (NO2-) by means of the Griess reaction. RESULTS: Histamine upregulates the generation of NO both in rat MCs and in guinea pig hearts. The effect is abolished by blocking NO synthase and preferentially mimicked by a selective H2-receptor agonist. A selective H3-receptor agonist downregulates the generation of NO in lipopolysaccharide-pretreated MCs and in bradykinin-pretreated guinea pig hearts. CONCLUSION: A mutual relationship between histamine and NO in allergic inflammation could be envisaged.

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In the last 5 years 16 patients with cholecystosis were observed. In this period the most recent diagnostic and therapeutic techniques were used including ultrasound which allowed to diagnose 60% of adenomyomatosis, 33.3% of cholecystosis and 6.7% of gallbladder polyposis. In 6 cases a traditional open surgery cholecystectomy was performed, while the videolaparascopic approach was used in other 6 cases. Histologic examination always confirmed the preoperative diagnosis, however in one case a gallbladder cancer was histologically found; this case had been clinically diagnosed 9 years previously as adenomyomatosis. Therefore, our experience suggest, in agreement with others, that cholecystosis should be considered as a precancerous lesion.

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In the last 3 years, 300 consecutive patients (110 men, 190 women) were treated for gallstone disease using either traditional open surgery or the video laparoscopic approach. The relative clinical data and results were compared and analysed. The Authors conclude that video laparoscopy presents a number of advantages such as minor costs, reduced pain, quick return to work, compared to traditional surgery, especially when correctly indicated.

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Despite the fact that the relationship between platelets and the inflammatory and immune responses has been reviewed previously, the allocation of platelets among the inflammatory cells is still at issue. Recent developments in our understanding of platelet-associated signalling events have offered new potential insights into platelet functions in inflammatory and immune-related diseases. In recent years, it has been established that a range of molecules, mainly associated with the platelet surface and/or the platelet granules, regulate the capacity of platelets to cross-talk with other inflammatory cells during the process of inflammation, and of vascular inflammation in particular. This is the case with platelet-derived growth factor (PDGF), secreted from platelet alpha-granules, with P-selectin, expressed on the platelet surface, and with platelet histamine, which is secreted from platelets in response to aggregatory and inflammatory stimuli. The nature and mechanism of action of these regulatory molecules, physiologically present in platelets and mobilised upon platelet activation and aggregation, is the subject of this review. The participation of platelets, through PDGF, P-selectin and histamine, is also discussed in overtly inflammatory disorders, such as acute respiratory distress syndrome, mesangial glomerulonephritis, chronic inflammatory bowel disease, disseminated intravascular inflammation, and allergic vasculitis, focusing on possible pharmacological interventions specifically active against growth factors, adhesion molecules and platelet histamine.

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Ninety-eight consecutive patients with ampullary and periampullary carcinoma diagnosed between 1983-1993 were studied retrospectively. Among these patients, 66 had a carcinoma of the head of the pancreas, 10 a carcinoma of the papilla of Vater, 8 a carcinoma of the duodenum, and 14 a carcinoma of the distal common bile duct. Resectability rate ranged from 12% to 90% according to the tumor location and histologic type. Palliative procedures such as laparotomy, biopsy and bilio-digestive bypasses were performed in 27 patients. Curative resections were performed in 24 cases: 20 pancreatoduodenectomies, 2 total pancreatectomies, 1 duodenectomy, 1 common bile duct resection. The results of the surgical treatment as well as mortality and morbidity rates were compared with those of different and larger series.

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A reappraisal of the results obtained after potentially curative resection for rectal cancer compared with "historical" results is reported. An increase of the overall survival rates was registered as well as a corresponding lowering of the pelvic recurrences: 4.54% in the group of patients with a-two-year follow up. As for relapse surgery, however, reviewing the series from January 1991 to December 1994, the results are still poor because relapses were not resectable in 85.7% of the cases.

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In the last 5 years 25 patients (11 men, 14 women) with carcinoma of the extrahepatic biliary duct were studied. The most frequent localization of the carcinoma was the hepatic hilum. D.C.P. according to Whipple was possible only in one patient, while in 20 patients a palliative approach with external and internal biliary derivations was the choice. In the remaining 4 patients an explorative laparotomy with biopsy was performed. It is concluded that palliative resection allows for a better quality of life.

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A review of 285 patients operated for colo-rectal cancer in order to evaluate cholecystectomy rate in their pathologic history is reported. A surprisingly high rate (9.47%) was registered also when compared with Literature data. Although not definitely conclusive for a positive correlation between cholecystectomy and colo-rectal cancer, the Authors believe that this study identifies a subgroup of patients potentially at risk for colo-rectal cancer. In these subjects a prophylactic, periodic colonoscopy could be useful.

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