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.
Several preparations of Cremophor E1, several of other non-ionic detergents and several components of Cremophor E1 were tested for their histamine-releasing capacity in dogs. Lutensol AP 10 and a derivative of 1,2-propylenglycol were ineffective, but showed excellent properties as detergents. Thus the histamine-releasing capacity was not necessarily combined with the tenside effect of the surfactants. Oleic acid found in Tween 80 as well as in Cremophor E1 seems to be the most effective constituent, but the alcohol seems also to be important for the histamine-releasing capacity. The development of a non-toxic solubilizer for lipophilic drugs seems of considerable clinical interest.
A new, highly sensitive and specific method for the fluorometric determination of histamine in human whole blood and plasma is described. The fluorescence spectra and the rate of inactivation by 165-fold purified diamine oxidase from pea seedlings and 120-fold purified histamine methyltransferase from pig antrum mucosa are identical for authentic histamine and the substance isolated from the human plasma. Diamine oxidase was purified by the precipitation of proteins at pH 5.0, ammonium sulphate fractionation at 35 and 65% saturation and by gel filtration on Sephadex G-100. Histamine methyltransferase was purified by ultracentrifugation, ammonium sulphate fractionation at 60 and 80% saturation, chromatography on DEAE cellulose and gel filtration on Sephadex G-. Spermidine did not interfere with the assay of histamine.The normal histamine concentration in human plasma was found to be 0.69 ± 0.26 ng/m/, in human whole blood 54 ± 18 ng/m/. The content of basophil granulocytes in whole blood was shown to be 70 ± 23 cells/mm 3 , whereby more than 90% of histamine in whole blood was localized in basophils. The histamine content of a single basophil granulocyte was calculated to be 1.2 ± 0.4 pg. In a patient, who showed severe anaphylactoid incidents to the anesthetic Propanidid, the plasma contained an average of 7.4 ± 3.2ng histamine/m/. This plasma histamine level is 10-fold higher than the normal values described above. With the aid of the new fluorometric method it seems now possible to investigate the role of histamine in various physiological and pathophysiological processes.
Eine hochempfindliche und spezifische Methode zur Bestimmung von Histamin in menschlichem Vollblut und PlasmaZusammenfassung: Eine neue, hochempfindliche und spezifische Methode wird für die fluorometrische Bestimmung von Histamin im menschlichen Vollblut und Plasma beschrieben. Die Fluoreszenzspektren und die Inaktivierungsgeschwindigkeit durch 165fach angereicherte Erbsen-Diamin-Oxidase und 120fach angereicherte Histamin-Methyltransferase aus Schweineantrum waren für Standardhistamin und die aus Plasma isolierte Substanz identisch. Diamin-Oxidase wurde angereichert durch Säurefällung bei pH 5,0, Ammoniumsulfatfraktionierung bei 35 und 65% Sättigung und
SummaryAlthough histamine release is recognised as a common event during anaesthesia and surgery, few clinicians judge the resultant cardiorespiratory disturbances serious enough to warrant prophylaxis with antihistamines. We have assessed the incidence and importance of histamine release in a randomised 2 × 2 factorial study. 240
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