Changes in bronchial hyperresponsiveness following high- and low-sulphite wine challenges in wine-sensitive asthmatic patients

BACKGROUND: Previous studies suggest that challenge of most wine-sensitive asthmatic patients may not result in a reduction in forced expiratory volume in 1 s (FEV(1)). OBJECTIVE: The aim of this study was to assess whether changes in bronchial hyperresponsiveness (BHR) occur following wine challenge of asthmatic patients who report sensitivity to wine, and whether such changes could help clarify the role of sulphite additives in wine-induced asthmatic responses. METHODS: Eight self-reporting wine-sensitive asthmatic patients completed double-blind challenges with high- and low-sulphite wines on separate days. FEV(1) and histamine PC(20) were measured before and after consumption of 150 mL of wine. RESULTS: None of the eight subjects demonstrated a clinically significant >or=15%) reduction in FEV(1) following challenge with either high- or low-sulphite wine. In contrast, one patient demonstrated clinically significant increase in BHR following challenge with both high- and low-sulphite wines, and a smaller increase in BHR following placebo challenge. A second patient showed a significant increase, while another showed a significant decrease in BHR following challenge with low-sulphite wine. A fourth patient showed borderline increases in BHR following challenge with both high- and low-sulphite wines. CONCLUSIONS: Although changes in BHR, in the absence of reductions in FEV(1), were observed in some asthmatic patients following wine challenge, these changes were not consistent with a single aetiology. Consequently, this study did not support a major role for the sulphite additives in wine-induced asthmatic responses in the patients studied. The aetiology of wine-induced asthma is likely to be complex and appears to vary among individuals who are sensitive to these drinks.     

A Case of Codeine Induced Anaphylaxis via Oral Route

Codeine is widely prescribed in clinical settings for the relief of pain and non-productive coughs. Common adverse drug reactions to codeine include constipation, euphoria, nausea, and drowsiness. However, there have been few reports of serious adverse reactions after codeine ingestion in adults. Here, we present a case of severe anaphylaxis after oral ingestion of a therapeutic dose of codeine. A 30-year-old Korean woman complained of the sudden onset of dyspnea, urticaria, chest tightness, and dizziness 10 minutes after taking a 10-mg dose of codeine to treat a chronic cough following a viral infection. She had previously experienced episodes of asthma exacerbation following upper respiratory infections, and had non-atopic rhinitis and a food allergy to seafood. A skin prick test showed a positive response to 1-10 mg/mL of codeine extract, with a mean wheal size of 3.5 mm, while negative results were obtained in 3 healthy adult controls. A basophil histamine release test showed a notable dose-dependent increase in histamine following serial incubations with codeine phosphate, while there were minimal changes in the healthy controls. Following a CYP2D6 genotype analysis, the patient was found to have the CYP2D6*1/*10 allele, indicating she was an intermediate metabolizer. An open label oral challenge test was positive. To the best of our knowledge, this is the first report of a patient presenting with severe anaphylaxis after the ingestion of a therapeutic dose of codeine, which may be mediated by the direct release of histamine by basophils following exposure to codeine.     

Incomplete digestion of codfish represents a risk factor for anaphylaxis in patients with allergy

BACKGROUND: Fish represents one of the most important allergenic foods causing severe allergic reactions. Nevertheless, it has been shown that gastric digestion significantly reduces its allergenic capacity. OBJECTIVE: In this study, we assessed the absorption kinetics of fish proteins and investigated the clinical reactivity of patients with fish allergy to codfish digested at physiological or elevated gastric pH. METHODS: Healthy individuals were openly challenged with codfish and blood samples were evaluated by histamine release for absorbed fish allergens. Patients with allergy were recruited on the basis of previously diagnosed codfish allergy. Fish extracts were digested with gastric enzymes at pH 2.0 and 3.0 and used for histamine release, skin prick tests, and titrated double-blind placebo-controlled food challenges. RESULTS: Ingestion experiments in subjects without allergy revealed absorption of biologically active fish allergens only 10 minutes after ingestion with maximal serum levels after 1 to 2 hours. Incubation of fish proteins with digestive enzymes at pH 2.0 resulted in a fragmentation of the proteins leading to a reduced biological activity evidenced by a significantly smaller wheal reaction and reduced histamine release. Fish digested at pH 3.0 revealed comparable reactivity patterns as undigested extracts. Moreover, these test materials triggered reactions at 10-fold to 30-fold lower cumulated challenge doses in patients with allergy. CONCLUSION: Our data indicate the paramount importance of gastric digestion for fish allergens because the quantitatively significant absorption and elicitation of symptoms seemed to take place in the intestine. CLINICAL IMPLICATIONS: Hindered digestion puts patients with fish allergy at risk to develop severe allergic reactions at minute amounts of allergens.     

Intolerance to dietary biogenic amines: a review.

OBJECTIVE: To evaluate the scientific evidence for purported intolerance to dietary biogenic amines. DATA SOURCES: MEDLINE was searched for articles in the English language published between January 1966 and August 2001. The keyword biogenic amin* was combined with hypersens*, allerg*, intoler*, and adverse. Additionally, the keywords histamine, tyramine, and phenylethylamine were combined with headache, migraine, urticaria, oral challenge, and oral provocation. Articles were also selected from references in relevant literature. STUDY SELECTION: Only oral challenge studies in susceptible patients were considered. Studies with positive results (ie, studies in which an effect was reported) were only eligible when a randomized, double-blind, placebo-controlled design was used. Eligible positive result studies were further evaluated according to a number of scientific criteria. Studies with negative results (ie, studies in which no effect was reported) were examined for factors in their design or methods that could be responsible for a false-negative outcome. Results of methodologically weak or flawed studies were considered inconclusive. RESULTS: A total of 13 oral challenge studies (5 with positive results and 8 with negative results) were found. Three of them (all with positive results) were considered ineligible. By further evaluation of the 10 eligible studies, 6 were considered inconclusive. The 4 conclusive studies all reported negative results. One conclusive study showed no relation between biogenic amines in red wine and wine intolerance. Two conclusive studies found no effect of tyramine on migraine. One conclusive study demonstrated no relation between the amount of phenylethylamine in chocolate and headache attacks in individuals with headache. CONCLUSIONS: The current scientific literature shows no relation between the oral ingestion of biogenic amines and food intolerance reactions. There is therefore no scientific basis for dietary recommendations concerning biogenic amines in such patients.     

Late-onset anaphylaxis to fermented soybeans: the first confirmation of food-induced, late-onset anaphylaxis by provocation test.

BACKGROUND: Late-onset anaphylactic reactions without early-phase reactions are rarely reported. The hypothesized mechanism of late-onset anaphylaxis to fermented soybeans is delayed absorption or release into the bowel rather than an immunologic phenomenon. OBJECTIVES: To investigate the mechanisms of late-onset anaphylaxis to fermented soybeans in 2 patients and to characterize the allergens involved in anaphylaxis caused by fermented soybeans. METHODS: Two patients underwent skin prick-by-prick tests with fermented soybeans as is. We used an open challenge for the provocation test of anaphylaxis and measured changes in plasma histamine, plasma tryptase, serum eosinophil cationic protein, and plasma leukotriene B4 levels in 1 patient. In addition, specific IgE against fermented soybeans and the allergens of fermented soybeans were detected by enzyme-linked immunosorbent assay and immunoblotting, respectively. RESULTS: The results of the prick-by-prick tests with fermented soybeans as is were positive in both patients and negative in control subjects. The challenge with 50 g of fermented soybeans caused generalized urticaria and dyspnea 13 hours after ingestion of fermented soybeans in 1 patient. In addition, his plasma histamine and tryptase levels transiently elevated during the anaphylactic event. In enzyme-linked immunosorbent assay, the patients showed elevated IgE levels to the proteins of fermented soybeans. Serum IgE antibodies of patients 1 and 2 were bound to approximately 5- and 26-kDa proteins in immunoblotting of fermented soybeans, respectively. CONCLUSION: To our knowledge, this is the first report of late-onset anaphylaxis provoked by the challenge test half a day after ingestion of fermented soybeans.     

Red and white wine differently affect collagen-induced platelet aggregation

Moderate consumption of wine is associated with reduced cardiovascular events, but the mechanism is not fully elucidated. Aim of the study was to seek if consumption of red or white wine, that are known to have different amount of polyphenols, differently influenced platelet aggregation. 20 healthy subjects were randomly allocated to consume for two weeks 300 ml of red or white wine; both wines had the same concentration of alcohol. At baseline and 12 hours after last drink collagen-induced platelet aggregation was performed. At baseline no difference of laboratory values was observed between the two groups. At the end of treatment subjects given red wine had lower response to platelet agonist than those given white wine (<0.005). No ethanol could be found in plasma 12 hours after last drink. This study shows that red and white wine have different effect on platelet activation likely because of the different content of polyphenols present in the two types of wine.     

Anaphylaxis to wine

Anaphylaxis following the ingestion of wine was found in a non-atopic woman. The reaction occurred within 15 min of wine ingestion but did not follow other alcoholic beverages. An immediate skin test response to the offending wine was found but specific IgE levels could not be measured by radioallergosorbent testing.     

Efficacy of ebastine, cetirizine, and loratadine in histamine cutaneous challenges.

BACKGROUND: Few studies have compared the antihistaminic effect of ebastine at 20 mg/day (maximal recommended daily dose) with the effect found for other antihistamines in human pharmacologic models. OBJECTIVE: To compare the inhibition of the histamine-induced skin reaction produced by ebastine (20 mg/day) with that produced by cetirizine (10 mg/day), loratadine (10 mg/day), or placebo in a double-blind, randomized, crossover, placebo-controlled clinical trial. METHODS: Twenty volunteers (10 men and 10 women) received the four treatments once daily for 7 days, with a mean 7-day washout period between treatments. Three intradermal histamine challenges (0.05 mL of a 100 microg/mL histamine solution at 4, 8, and 24 hours after drug administration) were performed at baseline, day 1 (single dose), and day 7 (multiple doses). Wheal and flare areas were measured after 15 minutes. RESULTS: All treatments yielded significant reductions of histamine-induced wheal in comparison to placebo (P < 0.001). Analysis of covariance revealed significant differences between treatments (P < 0.05). Ebastine had a significantly greater antihistaminic effect than did cetirizine or loratadine, except at 4 hours after a single dose versus cetirizine. Further, the effect of cetirizine was similar with single or multiple doses after both 4 and 24 hours, whereas the effect of ebastine showed significant increases in wheal reduction with multiple doses (P < 0.05). No serious adverse events or withdrawals occurred during the study. CONCLUSION: This study shows that ebastine in a 20-mg dose is an effective once-daily antihistamine. Superior efficacy was found in comparison to cetirizine (10 mg) or loratadine (10 mg) on the overall skin wheal response after single and multiple doses.     

Risk factors for acetaminophen and nimesulide intolerance in patients with NSAID-induced skin disorders.

BACKGROUND: Previous studies show skin reactions after exposure to acetaminophen and/or nimesulide to occur in about 10% of patients with a history of urticaria induced by aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). This fact is surprising since cross-reactivity among different NSAIDs should not occur among subjects without a history of chronic urticaria. OBJECTIVE: To detect risk factors for intolerance to alternative drugs such as acetaminophen and nimesulide in different groups of patients with a history of adverse skin reactions (urticaria/angioedema, or anaphylaxis) after the ingestion of aspirin and other NSAIDs. METHODS: Two hundred fifty-six patients with a history of recent pseudoallergic skin reactions caused by NSAIDs underwent elective oral challenges with increasing doses of both acetaminophen and nimesulide. Patients were divided into three groups: A = 69 subjects with chronic urticaria, B = 163 otherwise normal subjects with a history of urticaria after the ingestion of aspirin, and C = 24 otherwise normal subjects with a history of urticaria after the ingestion of pyrazolones but aspirin-tolerant. RESULTS: Forty-eight (19%) patients reacted to acetaminophen and/or nimesulide. Similar numbers of patients with chronic urticaria (23%) and of normal subjects with a history of aspirin-induced urticaria (19%) did not tolerate one of the alternative drugs challenged. Pyrazolones-intolerant patients showed the lowest number of reactors (4%). Aspirin intolerance represented a risk factor for acetaminophen- and/or nimesulide-induced urticaria (RR = 5.4). A history of anaphylactoid reactions induced by NSAID represented a risk factor for urticaria after the ingestion of the alternative study drugs (RR = 5.7). Atopic status was associated with a higher risk of reactivity to nimesulide: this drug induced urticaria in 11/47 (23%) atopics versus 18/209 (9%) non-atopics (P < .005; RR = 3.2). A history of intolerance to antibacterial drugs was not associated with a higher prevalence of reactivity against acetaminophen and/or nimesulide. CONCLUSIONS: In at least 20% of patients with a history of urticaria/angioedema or anaphylaxis induced by aspirin or other NSAIDs, but without a history of chronic urticaria, cross-reactivity with other NSAIDs occurs. Atopy as well as a history of aspirin-induced anapylactoid reactions seem to represent relevant risk factors for intolerance to alternative NSAIDs. In view of these findings, aspirin-intolerant patients with such clinical features should be submitted to peroral tolerance tests with at least two alternative substances in order to avoid potentially severe reactions.     

Adverse reactions to wine: think outside the bottle

PURPOSE OF REVIEW: Wine contains chemical and biological contaminants. Symptoms such as facial flushing, asthma and oral allergic swelling and burning (oral syndrome) have been attributed to these contaminants and food additives. Their clinical implications should be known. RECENT FINDINGS: Recent studies have reported a high prevalence of hypersensitivity symptoms after intake of alcoholic drinks in the general population. Red wine was the most common beverage implicated. Wine contains many contaminants. Some of them come from Hymenoptera insects that fall into the wine when grapes are collected and pressed. We have found patients with allergic symptoms related to wine consumption who are sensitized to Hymenoptera venom without previous stings. The aim of this study is to assess the potential importance of their sensitization to Hymenoptera antigens as the cause of their symptoms and also to comment on other recent studies on wine hypersensitivity. SUMMARY: We found patients with allergic symptoms related to wine consumption who are sensitized to Hymenoptera venoms. Challenges were negative with sulfites, other additives and aging wines, but positive with young wines. Sera from all the patients detected Hymenoptera venom antigens. We report the first cases of sensitization to venom antigens by the oral route.     

Mast-cell-dependent histamine release after praziquantel treatment of Schistosoma japonicum infection: implications for chemotherapy-related adverse effects

As previously shown, the development of adverse effects in praziquantel treatment of Schistosoma japonicum infection involves host anaphylactic reactions associated with a rapid elevation of the level of plasma histamine. This study, using genetically mast-cell-deficient mice, aimed at identifying the major source of plasma histamine released after praziquantel treatment. Mast-cell-deficient mice and congenic normal mice were treated with praziquantel 8 weeks after infection with S. japonicum. In normal congenic mice, the plasma histamine level at 60 min after chemotherapy was substantially higher (mean+/-SD: 123.34+/-23.13 ng/ml) than that in mast-cell-deficient mice (7.02+/-3.48 ng/ml). These results show that mast cells play a predominant role in the rapid increase of the plasma histamine level. Despite their lack of increase in plasma histamine, mast-cell-deficient mice exhibited post-praziquantel systemic signs but not histopathologic alterations due to allergic reactions, suggesting that unidentified mechanism(s) also contribute to the development of adverse post-praziquantel effects.     

IgE-mediated hypersensitivity to taugeh (sprouted small green beans)

This report describes a case of allergy toward taugeh (sprouted small green beans), an important constituent of eggroll. With use of the skin prick test, RAST, and histamine release test, IgE antibodies against taugeh extract could be demonstrated. A partial cross-reactivity was observed between IgE-binding components from taugeh and peanuts. Peanut allergic patients could also experience adverse reactions after ingestion of taugeh.     

Histamine-free diet: treatment of choice for histamine-induced food intolerance and supporting treatment for chronical headaches

Histamine-induced food intolerance is not IgE-mediated. Skin-prick testing and specific IgE to food allergens are typically negative. Food rich in histamine or red wine may cause allergy-like symptoms such as sneezing, flush, skin itching, diarrhoea and even shortness of breath. The suspected reason is a diminished histamine degradation based on a deficiency of diamine oxidase. As diamine oxidase cannot be supplemented, a histamine-free diet was implemented to reduce histamine intake. Forty-five patients with a history of suffering from intolerance to food or wine (n = 17) and chronic headache (n = 28) were put on the diet over months to years. Fish, cheese, hard cured sausages, pickled cabbage and alcoholic beverages had to be avoided. Complaint intensity and drug-use per week prior to and 4 weeks after a histamine-free diet were compared. After 4 weeks on the diet 33/45 patients improved considerably (P < 0.01), eight of them had total remission. In 12/45 patients, however, no changes in symptoms were observed. Symptoms of food or wine intolerance significantly decreased (P < 0.02; treatment of choice), headaches decreased in frequency (P < 0.001), duration and intensity. After eating histamine-rich food symptoms were reproducible and could be eliminated by anti-histamines in most patients. These data indicate the role of histamine in food and wine intolerance and that histamine-rich food causes a worsening of symptoms in patients suffering from chronic headaches. Results obtained support the hypothesis of a deficiency of diamine oxidase in patients with intolerance to food or wine.     

Evidence that histamine is the causative toxin of scombroid-fish poisoning

BACKGROUND. The highest morbidity worldwide from fish poisoning results from the ingestion of spoiled scombroid fish, such as tuna and mackerel, and its cause is not clear. Histamine could be responsible, because spoiled scombroid fish contain large quantities of histamine. Whether histamine is the causative toxin, however, has remained in question. To address this issue, we investigated whether histamine homeostasis is altered in poisoned people. METHODS. The urinary excretion of histamine and its metabolite, N-methylhistamine, was measured in three persons who had scombroid-fish poisoning (scombrotoxism) after the ingestion of marlin. We measured 9 alpha, 11 beta-dihydroxy-15-oxo-2,3,18,19-tetranorprost-5-ene-1,20-dioic acid (PGD-M), the principal metabolite of prostaglandin D2, a mast-cell secretory product, to assess whether mast cells had been activated to release histamine. RESULTS. The fish contained high levels of histamine (842 to 2503 mumol per 100 g of tissue). Symptoms of scombrotoxism--flushing and headache--began 10 to 30 minutes after the ingestion of fish. In urine samples collected one to four hours after fish ingestion, the levels of histamine and N-methylhistamine were 9 to 20 times and 15 to 20 times the normal mean, respectively. During the subsequent 24 hours, the levels fell to 4 to 15 times and 4 to 11 times the normal values. Levels of both were normal 14 days later. PGD-M excretion was not increased at any time. Two persons treated with diphenhydramine had prompt amelioration of symptoms. CONCLUSIONS. Scombroid-fish poisoning is associated with urinary excretion of histamine in quantities far exceeding those required to produce toxicity. The histamine is most likely derived from the spoiled fish. These results identify histamine as the toxin responsible for scombroid-fish poisoning.     

Plasma histamine in pig: Effect of food and pentagastrin

Histamine may have a role in the physiological control of gastric acid secretion. We aimed to detect histamine release into the circulation during food and pentagastrin. Non-parametric statistical analysis was used. Seven pigs bearing iliac artery, iliac vein and portal vein cannulae were given a standard meal. Blood samples were collected at 10-minute intervals over a period of 2 hours for histamine assay. There were no significant changes in whole blood and plasma histamine concentrations in the iliac arterial or venous blood. In portal venous blood, no significant changes were observed in whole blood histamine, but there were signficant increases in plasma histamine 40 minutes after food (basal median: 149.0; range: 50.3–258.6 pmol ml^–1; 40 minutes, median 214.9; range: 64.2–319.6 pmol ml^–1).Four pigs were given pentagastrin, 6 kg^–1 h^–1 i.v. Iliac and portal venous bloods were collected for histamine assay before and 15 minutes after pentagastrin infusion. There were no significant changes in the whole blood histamine concentration in either iliac or portal venous blood. A small increase, mean 5%, of plasma histamine concentration was detected in the iliac venous blood (basal mena 242.9±21.7 pmol ml^–1; stimulated mean 256.9±39.1 pmol ml^–1). A 20% increase in the portal plasma histamine concentration was observed after pentagastrin (basal mean 240.1±13.2; stimulated mean 288.4±18.8 pmol ml^–1).Both food and pentagastrin increase plasma histamine concentration in the portal vein. Pentagastrin has a greater effect than food.     

Sera from patients with multiple drug allergy syndrome contain circulating histamine-releasing factors

BACKGROUND: A subset of drug-intolerant patients show a marked propensity to react to several chemically unrelated antibacterial drugs. This condition is termed multiple drug allergy syndrome (MDAS). The pathogenesis of MDAS is still unclear. A possible mechanism is that a nonspecific patient-related factor leading to direct histamine release from mast cells and basophils is involved. We investigated whether a patient-related facilitating factor such as the clinically unapparent presence of circulating histamine-releasing factors may represent a nonspecific mechanism underlying drug-induced histamine release in patients with MDAS. METHODS: 38 otherwise healthy adults with a history of acute urticaria following the ingestion of antibacterial drugs [18 subjects with MDAS (patients) and 20 monosensitive subjects (drug-allergic controls) on the basis of both clinical history and single-blind peroral challenges with alternative substances] and 20 subjects without a history of drug allergy (normal controls) underwent an autologous serum skin test (ASST). IgE specific for beta-lactams was measured in sera from 25 subjects (11 patients and 14 drug-allergic controls) with a history of amoxicillin intolerance. Sera from 13 patients and 5 drug-allergic controls (all positive on ASST) were used in the in vitro histamine release assay using basophils from 3 normal donors. RESULTS: 17 of 18 patients (94%) versus 8 of 20 drug-allergic controls (40%) showed an unequivocal wheal-and-flare reaction on ASST (p < 0.05). Skin reactions were generally more intense in the patient group. In one MDAS patient, the ASST was not assessable due to dermographism. No normal control was positive on ASST. Sera from 3 of 13 patients (23%) versus 0 of 6 drug-allergic controls (not significant) induced significant histamine release from basophils of normal donors. IgE specific for beta-lactams was detected in sera from 1 of 11 patients (9%) versus 5 of 14 drug-allergic controls (36%) (not significant). CONCLUSION: Most patients with MDAS and more than one third of subjects with a history of hypersensitivity to a single antibacterial drug were characterized by the presence of circulating histamine-releasing factors. Such factors might play a role in drug-induced adverse reactions observed in these patients.     

The effect of inhaled allergen on circulating basophils in atopic asthma.

There is increasing evidence for the role of basophils in the allergen-induced late asthmatic response (LAR). To study the effect of inhaled allergen on basophil function in subjects with asthma, ex vivo basophil spontaneous histamine release (SHR) in peripheral blood and plasma histamine was measured before and 2, 5, 10, and 15 minutes, and 2, 4, 6, and 8 hours after allergen bronchial challenge (allergen study day) in six subjects with atopic asthma. Allergen inhalation induced an early response and LAR consisting of a mean (+/- SD) 32.5% (+/- 7.9%) and 28.8% (+/- 7.7%) fall in FEV1, respectively. As a control for the effects of bronchoconstriction, on another occasion, methacholine challenge was performed to produce a mean 33.4% (+/- 3.4%) fall in FEV1 during the early response and no LAR, and blood was obtained to measure basophil histamine release (HR) and plasma histamine. There was a small, but significant (p less than 0.05), rise in median SHR from 4.6% to 6.1% of total basophil histamine after allergen but not after methacholine inhalation. HR remained high after allergen inhalation during the 8 hours of study, whereas it demonstrated a steady, significant, decrease between 4 to 8 hours after methacholine inhalation. No significant changes in plasma histamine were recorded on either allergen or methacholine study days. On a third occasion, SHR was measured after challenge with physiologic saline to control for any effects of methacholine on SHR, and a decrease in HR was recorded during the day similar to HR observed after methacholine challenge. These studies suggest an enhancing effect of inhaled allergen on SHR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Onset of action of a topical antihistamine as assessed by histamine challenge-induced plasma exudation responses.

BACKGROUND: Although usually administered orally, antihistamines are available also for topical use in allergic rhinitis. Information on onset of action of these drugs is incomplete. OBJECTIVE: To examine onset of action of topical cetirizine-dinitrate on plasma exudation evoked by repeated nasal histamine challenges. METHODS: A liposome formulation of cetirizine-dinitrate (2.44 mg per nasal cavity) was delivered via a nasal spray device as 2 consecutive actuations per nasal cavity in a placebo-controlled design. The nasal mucosal surface was challenged and lavaged with a histamine solution (100 microg/mL) 5, 15, 25, and 55 minutes after each treatment. In addition, the mucosa was lavaged with saline before each treatment. The lavage fluid levels of alpha2-macroglobulin were measured as an index of mucosal exudation (luminal entry) of plasma. RESULTS: Histamine produced significant increases in nasal lavage fluid levels of alpha2-macroglobulin at all observation points (5 through 55 minutes after treatment). Nasal cetirizine-dinitrate significantly inhibited this response at 5 and 15 minutes after treatment. CONCLUSIONS: The effect of topical cetirizine-dinitrate, as established by histamine challenge-induced mucosal exudation of plasma, has an early onset (ie, within 5 to 10 minutes).     

Histamine measurement in whole blood and cell supernatants

Histamine as an important mediator of the allergic reaction has been measured by a number of methods both in whole blood and cell supernatants after in vitro release. We compared the fluorometric histamine assay with two radioimmunoassays and studied detection limit, recovery, cross-reactivity and accuracy in buffer-based standards as well as the sensitivity after IgE-mediated in vitro release from washed cells and whole blood. Our data indicate that the double-antibody RIA (Pharmacia) can be used for studies of basophil histamine release in both whole blood and cell supernatants. Due to significant cross-reactivity to N-methyl-histamine it cannot be used for histamine determinations in plasma. The second radioimmunoassay using succinyl-glycine as an acylating reagent and monoclonal antibodies, which have been raised to acylated histamine, is the most sensitive assay without any cross-reactivity with methylhistamine.     

黄酒和红葡萄酒抑制LDLR~(-/-)小鼠MMP-2表达和动脉粥样硬化斑块形成

目的:观察黄酒是否能减轻动脉粥样硬化斑块的形成并探讨其可能机制。方法:48只6周龄LDLR-/-小鼠,以高脂+高蛋氨酸(标准饲料+10%油脂+1.25%胆固醇+1%L-蛋氨酸)喂养诱导形成高同型半胱氨酸血症并致动脉粥样硬化模型,随机分为:黄酒组、红葡萄酒组、酒精组和对照组,每组12只。14周后处死小鼠,检测血脂及血浆同型半胱氨酸;观察胸腹主动脉和主动脉窦部粥样硬化情况;免疫组化测定主动脉窦部MMP-2的表达;明胶酶谱法测定MMP-2的活性。结果:(1)4组间TC、TG、HDL-C水平无显著差别(P0.05),黄酒组血浆HCY分别较对照组、酒精组和红葡萄酒组显著下降(P0.01)。(2)与对照组比较,主动脉粥样硬化斑块面积黄酒组、红葡萄酒组和酒精组分别减少了33.7%、35.9%(P0.01)和6.5%(P0.05);与酒精组比较,黄酒组和红葡萄酒组主动脉粥样硬化面积差别同样显著(P0.01)。分别与对照组和酒精组比较,黄酒组和红葡萄酒组主动脉窦部粥样硬化面积减少同样显著差异(P0.01),黄酒组和红葡萄酒组间无显著差异(P0.05)。(3)与对照组比较,MMP-2的表达在黄酒组、红葡萄酒组和酒精组分别减少了26.3%、27.6%(P0.01)和5.7%(P0.05);MMP-2的活性在黄酒组、红葡萄酒组、酒精组分别减少了31.7%、32.5%(P0.01)和6.7%(P0.05)。结论:黄酒和红葡萄酒均能抑制MMP-2的表达和减轻动脉粥样硬化斑块的形成,这可能是它们对心血管系统保护作用的机制之一。