BackgroundPatients with gastrointestinal food allergy are characterised by increased production of mast cell derived mediators upon allergen contact and present often with unspecific symptoms. The aim of this study was to evaluate urinary histamine and methylhistamine excretion in patients with food allergy and to compare their values with food-tolerant controls.MethodsIn a retrospective case control study the urinary excretion parameters were analysed from 56 patients (40.9, 19 – 58 years) in whom later food challenge tests confirmed food allergy. During their diagnostic work-up urine was collected during a 12-h period under an unrestricted diet with staple foods and a hypoallergenic potato-rice-diet (each 2 days). Healthy controls underwent the same diet types to define normal excretion parameters. Urinary histamine and n-methylhistamine were determined by ELISA or tandem mass spectrometry, respectively, and were expressed as median (25 – 75% range, μg/mmol creatinine x m2BSA).ResultsDuring unrestricted diet urinary histamine was significantly higher in gastrointestinal food allergy than healthy controls (1.42, 0.9 – 2.7 vs 0.87, 0.4 – 1.3; p < 0.0001), while the difference between both groups became marginal during potato-rice diet (1.30, 0.7 – 2.1 vs 1.05, 0.5 – 1.5; p = 0.02).N-methylhistamine was found to be significantly elevated in gastrointestinal food allergy both during unrestricted diet (7.1, 5.0 – 11.2) and potato-rice diet (5.7, 3.7 – 8.7) compared to controls (p < 0.0001). Interestingly, urinary methylhistamine excretion (p < 0.004) and clinical symptom score (p < 0.02) fell significantly when the diet was switched from unrestricted to hypoallergenic food, but was not correlated with symptom scores.ConclusionsIn gastrointestinal food allergy significantly higher levels of urine histamine and methylhistamine excretion were found under unrestricted diet, reflecting an increased secretion of histamine due to offending foods. Measurement of urinary n-methylhistamine levels may help to find out patients with increased histamine production and/or food-allergen induced clinical symptoms, respectively.

IntroductionAllergy frequency is still increasing in industrial countries, but monitoring of allergic and inflammatory conditions may be difficult. The incidence of allergy and elevated IgE serum levels has been reported to decrease with age.The measurement of urinary excretion of N-tele-methylhistamine is a valuable diagnostic tool to monitor disease activity in allergic or inflammatory conditions (e. g. food allergy, inflammatory bowel diseases, microscopic colitis), but there are only rare data on histamine production and excretion in different periods of age in a healthy adult population [1]. Materials and methodsUrinary excretion of N-tele-methylhistamine was measured under standardised conditions in a healthy population of 54 adults (32 women, 22 men, mean age 45 ± 14 years, range 16 -72 years) without any medication [2]. Allergic, inflammatory or neoplastic diseases were excluded by allergy tests, endoscopy, histology and serology. The patients received an unrestricted diet, only avoiding typical histamine rich food [2], from 8 a. m. to 2 p. m. on two successive days. Subsequently, urine samples were collected on these two days over a period of 12 h (6 p. m. to 6 a. m.) [2,3]. 1 N HCL was added to the urine samples to avoid bacterial histamine production.Urinary methylhistamine was measured by RIA (Pharmacia) [2, 3] with intra-and interassay variations of 12.5 and 14.5 %. Intra-individual variation of N-methylhistamine was 21.6 ± 16.3 %. Since urinary excretion of N-methylhistamine may be influenced by renal function, weight and body seize, urine N-methylhistamine values were related to creatinine excretion (Beckman creatinine analyzer 2) [2, 3, 4], and concentrations of N-methylhistamine were expressed as mg/mmol creatinine ¥ m 2 body surface area (BSA) [2, 3, 5]. Serum creatinine was below 1.4 mg/dl in all patients.The mean value of the individual methylhistamine excretion was calculated from the excretion rates obtained at day 1 and 2. Results and discussionUrinary concentrations of N-methylhistamine showed a Gaussian distribution, with no significant differences between sex (males: 5.2 ± 2.3 mg/mmol creatine ¥ m 2 BSA; females: 4.3 ± 1.6 mg/mmol creatine ¥ m 2 BSA) and different age groups.Interestingly, urinary methylhistamine was found to be relatively stable between 4.0 and 5.2 mg/mmol creatinine ¥ m 2 BSA (± SD 1.3 -2.4) in different age groups (Fig. 1).In contrast to IgE, urinary excretion of N-methylhistamine showed no age-dependent differences in a healthy adult population, when standardised urine collection and evaluation criteria are used (diet, renal function, BSA) [2,3]. This result indicates a stable histamine production and metabolism in healthy adults with increasing age (Fig. 1) and it seems to be more modulated by allergic and inflammatory conditions, concomitant medication or disease and nutrition. There is only rare information about the relation of histamine metabolism and age. Oosting et al. found an age dependency Inflamm. res. 52, Supplement 1 (2003) Fig. 1. Urinary N-tele-methyl...

Summary: Antiviral therapy of human immundeficiency virus (HIV) infection is currently based on Inhibition of reverse transcriptase by dideoxynucleosides, such äs azidothymidine. Because of widespread toxicity it is reasonable to selectively target these drugs to infected cells. This may be accomplished utilizing drug-LDL conjugates, which are interüalized via cell specific receptor pathways. With respect to HIV infection, scavenger receptors of the macrophage System seems to offer a hopefull perspective. This pathway requires chemical modification of surface polarity of the LDL. Cell experiments were conducted in HepG2 hepatocytes, which express apolipoprotein B receptors, and in P 388 macrophages, which express scavenger receptors. LDL particles to be conjugated were isolated from blood donor plasma and from LDL-apheresis waste material. Noncovalent LDL conjugation with amphiphilic nucleoside derivatives produced only an unspecific nucleoside transfer to cell membranes, due to instability of the LDL conjugates. An experimental method (coincubation test) was developed to identify those conjugates that are stable in the presence of other lipophilic compartments. Covalent coupling pf nuclepsides to the apolipoprotein B moiety of LDL particles resulted in stable conjugates. As a consequence, the surfaee Charge became negative, and the LDL displayed scavenger receptor affmity rather than apolipoprotein B receptor affinity. Selective targeting of nucleosides to macrophages can be accomplished by covalent coupling to LDL.

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