In a randomized controlled trial, 30 pigs were orally treated with histamine (60 mg). In addition, half of the animals underwent a specific blockade of the enzyme diamine oxidase (DAO), which is the main histamine catabolising enzyme in the intestinal tract. Only these DAO-blocked animals exhibited severe clinical symptoms (e.g. hypotension, flush, vomiting) and, in parallel, showed tremendous elevations of plasma histamine levels of up to 160 ng/ml. 3 out of 15 animals in this group died within the experimental period. In contrast, the control animals neither exhibited plasma histamine levels above 5 ng/ml nor had any clinical reactions. These results contradict the current opinion that oral histamine intake in food is not clinically relevant, especially since many commonly used drugs are DAO-inhibitors and approximately 20% of our population take these drugs. Apart from drugs, some other factors (alcohol, spoilt food etc.) can also function via a blockade of DAO as an additional risk. DAO-blockade is therefore a real epidemiological problem. Evidence is presented here for the new disease concept: Food-Induced Histaminosis.

The aim of the present study was to compare the physical, chemical and biological parameters and the microbiological quality of bee-pollen samples treated with different dehydration processes and to correlate the results. The samples came mainly from Eucalyptus (Myrtaceae) and Eupatorium (Asteraceae) plants. The dehydration conditions of the samples influenced the L*a*b* colour parameters and the biological value. Unlike the protein and lipid content, the glucose and fructose content were unaffected. The vitamin E content (27.2 ± 0.3 mg/g, 27.5 ± 0.4 mg/g) in oven-dehydrated samples with forced air circulation was significantly lower (P < 0.05) compared with lyophilized samples (37.5 ± 0.2 g/100 g, 53.7 ± 3.9 g/100 g). Overall, the results were inconclusive for vitamin B complex, minerals and microbiological indicators. There was a positive correlation between the colour parameters L* and b* and the total phenolic content, as well as between phenolic content and the antioxidant and antimicrobial capacity. The data indicate that lyophilization might be a viable alternative to the current process, resulting in dehydrated bee-pollen with higher biological activity.

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Using a recently established porcine model, it was clearly shown that oral histamine administration is extremely dangerous in the presence of diamine oxidase (DAO) blockade. Due to the severity of the symptoms (20% death) and the clinical relevance, further interest has been focussed on strategies to prevent or alleviate food induced histaminosis. In a randomized controlled trial, 10 pigs under DAO blockade were challenged with oral histamine (60 mg). Half of these animals received a prophylactic premedication with a combination of H1- and H2-receptor antagonists. As expected, all animals developed a massive increase in plasma histamine levels, with significantly higher values in the control group (median: 123 ng/ml) compared to the antihistamine group (median: 32 ng/ml). In contrast, clinical symptoms were only observed in the control group. The maximum fall in mean arterial pressure (hypotension) was 60 mmHg (median for control group) but only 15 mmHg (median) under antihistamine pretreatment. These results firstly provide further evidence for the causal role of histamine in the new disease concept and secondly enable us to investigate appropriate therapeutic measures for patients at risk.

Three hundred and forty-one drugs, commonly used in intensive care units (ICU), were chosen for an investigation of possible activation or inhibition of the histamine metabolizing enzyme diamine oxidase (DAO). After examination of 164 substances, using both canine and human DAO in an in vitro screening test, 61 agents inhibited DAO activity to various degrees. Of these, 44 inhibited the enzyme from both species, 4 inhibited the canine enzyme only and 13 the human DAO only. No compound tested was able to enhance the enzyme activity. The inhibiting agents included representatives of all major therapeutic groups. A particularly strong inhibition was observed with the neuromuscular blocking drugs d-tubocurarine, pancuronium and alcuronium, however, the other commonly used neuromuscular blocking drug, suxamethonium, was without effect. Similarly with the cephalosporines, cefotiame and cefuroxime caused a marked inhibition of the human DAO activity, whereas another regularly-used substance of this class, cefotaxime, inhibited neither the human nor the canine enzyme in concentrations up to 10(-3) M. The observation that within a given therapeutic group some members inhibit and others do not, could be useful in choosing a therapy concept which minimizes the risk of a more severe 'histamine' reaction in seriously ill patients.

To understand the role of histamine in the aetiology and pathogenesis of human diseases reliable data are urgently needed for the histamine content and for the activities of histamine-forming and -inactivating enzymes in human tissues. In order to make a substantial progress toward this aim a tissue-sampling programme during surgical interventions was carefully conceived and conducted. From March 1982 until January 1983 106 tissue specimens were taken from 56 patients who underwent surgery. Only healthy tissues, not injured or oedematous, and without adherent structures were taken by only one surgeon who was interested in this research and experienced in tissue preparation procedures in biochemistry. The times of 'warm' ischaemia during the operative procedures were visually estimated, the times between resection of the organs or specimens and deep-freezing of the tissues were precisely recorded. Compared to previous work in the literature and especially to our own work using the same assays for determination higher histamine contents were found in this study in most of the tissues, in particular in the gastrointestinal tract. Also the diamine oxidase activities were considerably higher in many organs, e.g. 3-4 times higher in the gastrointestinal tract when compared with those in publications of our group who used always the same analytical test. However, the histamine methyltransferase activities in this study were not at variance to those determined in previous investigations. Many of them were reported in this communication for the first time. Since the methods for histamine determination and those for measuring enzymic activities were not different in this study and in previous communications of our group we are convinced that the optimized tissue-sampling and -preparation techniques were responsible for the higher values in this communication. But the problem of the 'warm' ischaemia period could not be solved by sample-taking procedures of this type during operations. There are good reasons to prefer biopsy specimens for the analysis of histamine storage and metabolism in human tissues in health and disease, but - unfortunately - they are not always available.