Metabonomics delineates allergic reactions induced by Shuang-huang-lian injection in rats using ultra performance liquid chromatography-mass spectrometry.

Shuang-huang-lian Injection (SHLI) is the first successfully developed drug from traditional Chinese medicine (TCM) powder for injection, since its use for the treatment of acute respiratory tract infection, pneumonia, influenza, etc. At the same time, its allergic reactions have also emerged, which limits clinical applications. However, few scholars pay attention to the mechanism of allergic reactions. In this present study, metabonomics technology was used to explore the changes in endogenous metabolites in urine of the rat model of SHLI induced allergic reaction; we and analyzed the metabolites, metabolic pathway, and the mechanism which were closely related to the allergic reactions. The levels of serum histamine and tryptase were examined and changes in histomorphology were also observed. Based on the UPLC-Q-TOF/MS metabonomics, we carried out the pattern recognition analysis, selected potential biomarkers associated with allergic reactions, and explored the pathological mechanism for SHLI induced allergic reaction, which laid the foundation for the safety research of SHLI. Our results showed that SHLI increased the levels of serum histamine and tryptase in rats with allergic reaction; we determined 15 biomarkers in rat allergic reaction model induced by SHLI and found multiple metabolic pathways involved, such as metabolism of linolenic acid, phenylalanine, amino acid, 2-oxo acid, and purine and other metabolic pathways.

Excretion of urinary histamine and N-tele methylhistamine in patients with gastrointestinal food allergy compared to non-allergic controls during an unrestricted diet and a hypoallergenic diet.

BACKGROUND: Patients 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. METHODS: In 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 m(2)BSA). RESULTS: During 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. CONCLUSIONS: In 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.

[Persistent udder edema as a herd problem: a literature review]. / Persisterend uieroedeem als bedrijfsprobleem: een literatuuroverzicht.

The data presented in literature suggest that disturbances of volume regulation do not have a role in the pathogenesis of persistent udder oedema. Instead, they favour local mammary problems. The presence of both mast cells and oedema, especially in subcutaneous tissue, focuses attention on the role of mast cells in the pathogenesis of persistent udder oedema via increased endothelial permeability due to histamine release. The dissociation constants (Kd) for the high-affinity glucocorticoid receptor of normal and oedematous udders are not significantly different, and nor are there differences between the total quantity of dexamethasone bound (Bmax) and mast cell density in normal and oedematous udders. It has been shown that, in cattle, the concentration of histamine is higher in milk than in plasma. In addition, the urine histamine concentration is affected by the diet. Treatments to reduce udder oedema include combined salt and water restriction, supplementation with potassium or vitamin E (alpha-tocopheryl acetate), sodium restriction, and administration of hydrochlorothiazide intramuscularly, chlorothiazide orally, or sodium-acetazolamide orally and/or parenterally (i.v./i.m.). A low cation-anion balance in a diet containing 1.6% calcium also seems to reduce mammary oedema formation.

The spectrum of mastocytosis.

Mastocytosis represents a spectrum of clinical disorders that results from an aberrant proliferation of tissue mast cells. This disease process may be confined to the skin (cutaneous mastocytosis) or may involve multiple organs (systemic mastocytosis). Parameters that are useful in differentiating cutaneous from systemic disorders include patient age, symptom complex, and clinical signs. A wide range of clinical symptoms may be encountered in patients with mastocytosis which result from the release of pharmacologically potent mast cell mediators. Distinct cutaneous patterns resulting from skin mast cell infiltrates can be helpful in identifying patients with systemic involvement. The diagnosis of mastocytosis is confirmed by demonstrating increased tissue mast cells in involved organs. The overall prognosis for patients with proliferative mast cell disease is relatively good, although a small percentage are at risk for developing a fatal neoplastic disorder (malignant mastocytosis). Treatment of mastocytosis is directed at both inhibiting mast cell degranulation and blocking the potential systemic effects of released secretory products. Future therapeutic advances depend upon an improved understanding of the basic mechanisms involved in mast cell mediator release and the forces that govern mast cell growth and development.

Effect of manual lymphdrainage massage on blood components and urinary neurohormones in chronic lymphedema.

In an earlier paper we have shown that manual lymph drainage massage of edematous limbs can result in the excretion of up to 1 liter urine derived from reabsorption and transport from the interstitial fluid, simultaneously with significant changes in the excretion of urinary neurohormones. These findings indicated that histamine and serotonin were released from the edematous tissue and that circulation improved through increased output of adrenaline and noradrenaline. The results achieved led us to assume that similar changes may have occurred in the blood during treatment, and induced us to study the effect of manual lymphdrainage on various blood constituents and urinary neurohormones.

Quantitative analysis of histamine in biological samples by gas chromatography--mass spectrometry.

A mass fragmentographic method for the quantitative analysis of histamine in the supernatant from antigen-challenged leukocytes, whole blood, and urine is described. Histamine labeled with two 15N atoms was synthesized and added to the sample as an internal standard. N alpha-Heptafluorobutyryl-N tau-ethoxycarbonylhistamine was prepared for mass fragmentographic analysis and the molecular ions at m/z 379 and 381 were used for monitoring histamine and 15N2-labeled histamine, respectively. The quantitation limit of histamine was 2 ng by this method. The experimental error of the method was less than 7% at the level of 5 ng in the supernatant from antigen-challenged leukocytes. The value obtained by this method correlated well with that from radioisotopic enzymatic assay (r=0.990).

Effect of manual lymph drainage massage on urinary excretion of neurohormones and minerals in chronic lymphedema.

Treatment of 29 cases of chronic lymphedema of various origins, mostly of the lower limbs, by manual lymph drainage massage resulted in significant changes of neurohormone excretion in the urine, whereas the secretion of 17-KS, thyroxine, minerals, and creatinine was not significantly changed. Comparison of the values of urinalysis before and after manual lymph drainage of the patients showed the following changes: 17-KS; -3.5% (non significant); 17-OH: -31% (significant); adrenaline: +50% (significant); noradrenaline: +19% (significant); serotonin: -22% (significant); 5-HIAA: +21% (significant); histamine: +129% (highly significant); thyroxine: -17% (nonsignificant); creatinine: -17% (nonsignificant); sodium: -1% (nonsignificant); potassium: -14% (nonsignificant). The corresponding values for ten controls were all non significant. These findings underline the importance of adrenaline and noradrenaline release by manual lymph drainage, which improves circulation. On the other hand, our results indicate the involvement of histamine and perhaps of serotonin in lymphedema formation, and suggest a combination of manual lymph drainage massage with antihistamine and antiserotonin treatment.

Techniques for measring histamine formation in mice.

1. Formation of (14)C-histamine from (14)C-L-histidine was studied in mice using various inhibitors of histamine catabolism; these included aminoguanidine, pargyline and methylhistamine, inhibitors of diamine oxidase, monoamine oxidase, and the histamine-methylating enzyme, respectively.2. Four general approaches were used: inhibiting diamine oxidase and the histamine-methylating enzyme and measuring (14)C-histamine in tissues or urine, or inhibiting diamine oxidase and monoamine oxidase and measuring (14)C-methylhistamine in tissues or urine. In some tests mice with normal concentrations of histidine decarboxylase were used; in others the enzyme was activated by pretreating mice with Freund's adjuvant.3. Methylhistamine pretreatment increased (14)C-histamine in several tissues of mice but aminoguanidine had no significant effect; it was concluded that endogenously formed histamine is inactivated almost entirely by methylation.4. There was no evidence of parallelism between the ability of tissues to form histamine and to inactivate endogenous histamine.5. Effects of Freund's adjuvant on tissue concentrations of (14)C-histamine were tested in mice with or without inhibitors of histamine catabolism. Results were essentially parallel in both cases but higher in the former.6. The method of choice is measurement of (14)C-histamine in tissues of mice given aminoguanidine and methylhistamine, followed by (14)C-L-histidine.7. Other approaches listed above may be useful but require improvement, for example, a more specific assay for (14)C-methylhistamine and a stronger, longer-lasting inhibitor of histamine-methylation.