The release of endogenous histamine (HA) from the hypothalamus of anesthetized rats was measured by in vivo microdialysis coupled with HPLC with fluorescence detection. Freshly prepared Ringer's solution was perfused at a rate of 1 microliter/min immediately after insertion of a dialysis probe into the medial hypothalamus, and brain perfusates were collected every 30 min into microtubes containing 0.2 M perchloric acid. The basal HA output was almost constant between 30 min and 7 h after the start of perfusion, with the mean value being 7.1 pg/30 min. Thus, the extracellular HA concentration was assumed to be 7.8 nM, by a calculation from in vitro recovery through the dialysis membrane. Perfusion with a high K+ (100 mM)-containing medium increased the HA output by 170% in the presence of Ca2+. Systemic administration of either thioperamide (5 mg/kg, i.p.), a selective H3 receptor antagonist, or metoprine (10 mg/kg, i.p.), an inhibitor of HA-N-methyltransferase, caused an approximately twofold increase in the HA output 30-60 min after treatment. The combined treatment with thioperamide and metoprine produced a marked increase (650%) in the HA output. The HA output decreased by approximately 70% 4-5 h after treatment with alpha-fluoromethylhistidine (alpha-FMH; 100 mg/kg, i.p.), an inhibitor of histidine decarboxylase. Furthermore, the effect of combined treatment with thioperamide and metoprine was no longer observed in alpha-FMH-treated rats. These results suggest that both HA-N-methyltransferase and H3 autoreceptors are involved in maintaining a constant level of extracellular HA and that their blockade effectively results in a higher activity level of the endogenous histaminergic system in the CNS.
Histamine (10−7 to 10−4 M) concentration-dependently stimulated the production of IL-18 and IFN-γ and inhibited the production of IL-2 and IL-10 in human PBMCs. Histamine in the same concentration range did not induce the production of IL-12 at all. The stimulatory or inhibitory effects of histamine on cytokine production were all antagonized by H2 receptor antagonists ranitidine and famotidine in a concentration-dependent manner, but not by H1 and H3 receptor antagonists. Selective H2 receptor agonists, 4-methylhistamine and dimaprit, mimicked the effects of histamine on five kinds of cytokine production. The EC50 values of histamine, 4-methylhistamine, and dimaprit for the production of IL-18 were 1.5, 1.0, and 3.8 μM, respectively. These findings indicated that histamine caused cytokine responses through the stimulation of H2 receptors. All effects of histamine on cytokine responses were also abolished by the presence of either anti-IL-18 Ab or IL-1β-converting enzyme/caspase-1 inhibitor, indicating that the histamine action is dependent on mature IL-18 secretion and that IL-18 production is located upstream of the cytokine cascade activated by histamine. The addition of recombinant human IL-18 to the culture concentration-dependently stimulated IL-12 and IFN-γ production and inhibited the IL-2 and IL-10 production. IFN-γ production induced by IL-18 was inhibited by anti-IL-12 Ab, showing the marked contrast of the effect of histamine. Thus histamine is a very important modulator of Th1 cytokine production in PBMCs and is quite unique in triggering IL-18-initiating cytokine cascade without inducing IL-12 production.
A simple and highly sensitive method for the determination of histamine (HA) was developed using ion-pair, reversed-phase HPLC coupled with postcolumn o-phthalaldehyde derivatization fluorometry, and it was applied to the unpurified extracts of human and rat plasma, and brains of rats and mice. The HA concentrations both in the plasma and brains determined by the present method were well consistent with the values obtained by cation-exchange HPLC with postcolumn fluorescent derivatization currently in use. The present method was more advantageous than the assay using cation-exchange HPLC: (1) it was three to four times more sensitive (the detection limit was 0.5 pg of HA), and (2) it enabled the measurement of HA in samples containing (R)alpha-methylhistamine, a potent and specific H3-receptor agonist, which could not be separated from HA by cation-exchange chromatography. Using the present method coupled with intracerebral microdialysis, we found in the rat hypothalamus that (R)alpha-methylhistamine (5 mg/kg i.p.) markedly decreased the extracellular concentration of HA with a maximal effect (83% reduction) during 30-60 min after injection, suggesting that most of HA in the microdialysate fraction is neuronal in origin.
LTHOUGH allergic reactions to barium sulfate suspensions are estimated to occur at a rate of less than 2 per million, 1,2 the frequency has been reported to be increasing. 3,4 The cause of these reactions is not known, 5-9 but the additives in barium suspensions, 10-13 medications such as glucagon, 3 and exposure to latex 14-17 -for example, through contact with rubber gloves or balloons -have all been implicated.We describe a patient with anaphylaxis induced by the carboxymethylcellulose sodium in barium sulfate suspension. The reaction occurred after an upper gastrointestinal examination. CASE REPORTA 63-year-old woman was admitted to the hospital in May 1994 because of an anaphylactic reaction after a double-contrast upper gastrointestinal examination. Before the examination, she had no abdominal discomfort. She had no history of atopic dermatitis, allergic rhinitis, or asthma and had not had any side effects from earlier barium studies. The examination was performed with a 100 percent (wt/vol) suspension of barium sulfate (Balgin S Solution number 3, Kaigen, Osaka, Japan) and gas-producing granules (Kaigen). No other medications were given. The examination revealed no gastritis or peptic ulcers. About 30 minutes later, the patient reported generalized pruritus and urticarial lesions on her abdomen, arms, and face, as well as mild periorbital edema. Within minutes she lost consciousness briefly and had tonic convulsions.On admission, a complete blood count, blood chemical values, and serologic tests were normal. Chest radiographs revealed no abnormalities. The white-cell count was 6400 per cubic millimeter, with 0.5 percent eosinophils. The patient again had transient loss of consciousness and hypotension. She was resuscitated with A subcutaneous injections of epinephrine (0.5 mg), intravenous infusion of fluids, and two injections of methylprednisolone sodium succinate (250 mg each). The urticarial lesions disappeared after 24 hours. The patient recovered fully and went home eight days later. METHODS Skin TestingAfter obtaining oral informed consent, we studied the patient and three healthy subjects without atopy or allergies. We conducted skin-scratch tests for each of the components of the barium suspension: barium sulfate, carboxymethylcellulose sodium, sodium metaphosphate, sodium benzoate, sodium dehydroacetate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, glacial acetic acid, saccharin sodium, and flavorings. All substances (purity, more than 98.0 percent) were mixed with petrolatum and liquid paraffin (10 percent wt/wt) and applied to the skin. The response was evaluated 20 minutes later. The patient also underwent skin-scratch testing with barium sulfate suspension that contained 1.2 percent carboxymethylcellulose sodium and with barium suspension free of carboxymethylcellulose. All the components of the suspension as well as the suspension that did not contain carboxymethylcellulose sodium were obtained from Kaigen. Histamine Release from Isolated LeukocytesPeripheral blood was withdrawn fr...
The anaphylactic histamine release from guinea-pig and rat lung tissues was com pletely or largely depressed by oxygen lack, respiratory inhibitors and uncouplers of oxidative phosphorylation when the incubation medium was devoid of glucose (1-7).Similar inhibition has been found of compound 48/80-induced histamine release from rat lung tissue and of degranulation of rat mesentery mast cells (6, 8, 9). Since these inhibitions were largely overcome by the presence of glucose (4-9), and phlorizin (10) and 2-deoxyglucose (7) inhibited these glucose-dependent release of histamine, glycolysis should be considered to take part in supplying the energy required for these processes.Chymotrypsin is also known to cause histamine release (11) and degranulation of mast cells (11, 12), and the latter action is also blocked by anoxia and glucose has a preven tive effect on this block.There are a number of works demonstrating the histamine-releasing or degranulat ing effect of compound 48/80 and some other agents including anti-serum ( In the present experiments, with isolated mast cells, the glucose-dependent degra nulation by compound 48/80, a-chymotrypsin and anti-serum is demonstrated under nitrogen anaerobiosis with success, and the effects of some inhibitors including phlorizin and 2-deoxyglucose are studied. Observations in aerobiosis are also described. METHODS AND MATERIALSIsolation of mast cells : Rats of both sexes weighing 150-300 g were bled by severance of carotid arteries. Five milliliters of buffered physiological solution [NaCI 154 mm ,
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