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Biogenic Amine Assays for Pharmaceutical and Specialty Research-summary product data: please request full insert for current and more detailed information

The following Elisa kits are manufactured by IBL (Immuno Biological Laboratories, Hamburg Germany) and distributed by RDI Divison of researchd Industries Intl for in vitro research use only-not for use in or on humans or animals, not for use in diagnostics.

Histamine ELISA  cat#RDI-RE59221

(replaces old cat#RDI-RE59201)

Enzyme Immunoassay for the Quantitative Determination of Histamine in Plasma, Urine and Cell Culture Supernatants. see also kits histamine in food stuffs (cat#RDI-RE59211) and histamine release

   Catalogue No :        RDI-RE59221  1Kit - $595.00
 Product group  : Allergy                             12 x 8      
 Product name   : Histamine                     ELISA   96
 Method         : ELISA                                                       
 Incubation time: 3 h, 40 min                                                 
 Standard curve : plasma: 0.67 - 162 ng/ml, urine/cell cult.: 2.7 - 219 ng/ml 
 Sample/Prep.   : 100 µl plasma, 50 µl urine or 50 µl cell culture supernatant
 Isotope/Substr.: TMB, 450 nm                                                 

Introduction In humans, histamine (ß-imidazolethylamine) is the most important mediator and is mostly found in the initial phase of an anaphylactic reaction ("immediate type" allergy). Histamine is metabolized by the enzymatic decarboxylation of histidine. In the organism, histamine is present in nearly all tissues, and it is mainly stored in the metachromatic granula of mast cells and the basophilic leukocytes. It is present in an inactive bound form and is only released as required. Histamine acts predominantly on smooth muscle and blood vessels. In humans, it is responsible for the bronchoconstriction occurring during the acute phase. In the vessels, its constrictive effect is limited to the venula, whereas arterioles are dilated. Furthermore, histamine causes a contraction of the cells of the vascular endothelium and increases the vascular permeability, thereby allowing higher-molecular substances to escape into the tissue. Like several other mediators, histamine does not only mediate various clinical symptoms of anaphylaxis but also induces a series of effects which are directed towards a termination of the anaphylactic reaction. Histamine may inhibit the release of lysosomal enzymes from polymorphonoculear leukocytes, the degranulation of mast cells and basophiles and the production of complement components through mononuclear phagocytes. Furthermore, histamine can activate suppressor T cells and, thus, may inhibit the production of IgE. The biological action of histamine in tissue is guaranteed by three different surface receptors, i.e. H1, H2 and H3 receptors. Of clinical interest in the histamine determination is the quantification of the histamine release from basophilic leukocytes in allergies of the "immediate type" as well as of the histamine quantity which is present in various body fluids (plasma, urine, cell culture supernatants), after allergen administration. First contact of the organism with an allergen does not result in the initiation of a histamine release. First, specific IgE antibodies are produced which migrate to the mast cells and there they bind to the receptors. At the second allergen contact, a transformation of a B cell to a plasma cell is no longer required. The allergen directly moves to the IgE antibodies already bound to the mast cells and binds to these antibodies. The mast cell responds by histamine secretion from its granula. The direct detection of mediator substances like histamine during an allergic reaction is not only of scientific interest but possibly also of practical importance in connection with a specific antagonistic therapy. IBL offers a supplementary kit for the performance of a Histamine Release test in heparinized whole blood.
Contents of the Kit 1. Assay Buffer, Concentrate 1 bottle 60 ml, TRIS buffer containing Tween and BSA, dilute 1:5 with bidist. water before use. 2. Acylation Reagent 1 vial 1.5 ml, ready for use, contains dimethylformamide. 3. Indicator Buffer 1 bottle 11 ml, ready for use, Tris buffer containing phenol red (colour change < pH 7.5). 4. Microtiter Strips 12 break apart strips 8 wells per strip, coated with goat-anti-rabbit antiserum. 5. Histamine Antiserum 1 bottle 6 ml, ready for use, antiserum from rabbit in TRIS buffer with stabilizers, blue coloured. 6. Plasma Standards A - G 7 vials for the determination of Histamine in plasma, lyophilized, dissolve contents of each vial in 0.4 ml bidist. water. Freeze aliquots at -20°C. For each lot of standards, refer to vial labels as well as to quality control certificate for exact concentrations. 7. U/Z Standard A/Diluent 1 vial 2.0 ml, ready for use. U/Z Standards B - F 5 vials each 0.25 ml, ready for use, standards for the determination of Histamine in urine and cell culture supernatants. Concentrations: Standard A B C D E F ng/ml 0 2.7 8.1 24.3 73 219 nmol/l 0 24.3 73 219 657 1971 8. Control Plasma 1 and 2 2 vials lyophilized, dissolve contents of each vial in 0.4 ml bidist. water before use. For histamine content see enclosed quality control certificate. Store dissolved controls at < -20°C 9. Urine Controls 1 and 2 2 vials each 0.25 ml, ready for use. For histamine content see enclosed quality control certificate. 10. Wash Buffer, Concentrate 1 bottle 50 ml, phosphate buffer with tween and stabilizers, dilute 1:20 with bidist. water before use. 11. Enzyme Conjugate, Concentrate 1 vial 75 µl, Histamine conjugated with peroxidase, dilute 1:200 with Assay Buffer. 12. TMB Substrate Solution, Concentrate 1 vial 1 ml, Tetramethylbenzidine (TMB) with stabilizers. 13. TMB Substrate Buffer 1 bottle 30 ml, ready for use, Hydrogenperoxide in citrate buffer with stabilizers. Store protected from light! 14. TMB Stop Solution 1 bottle 15 ml, ready for use, contains 1 M sulfuric acid. Corrosive! 15. Adhesive Foil 3 pieces

Principle of the Test

The HISTAMINE-ELISA kit provides materials for the quantitative measurement of acylated histamine in plasma, urine and cell cultures supernatants. The sample preparation, i.e. acylation of histamine to N-acylhistamine, is part of the sample dilution and is achieved by incubation of the respective sample with the "Acylation Reagent". The assay procedure follows the basic principle of the competitive ELISA: the competition between a peroxidase-conjugated and a non-conjugated antigen for a fixed number of antibody-binding sites (rabbit-anti-histamine). The peroxidase-conjugated antigen-antibody complexes bind to the wells of the microtiter strips which are coated with a goat-anti-rabbit antibody. Unbound antigen is then removed by washing. After the substrate reaction, the optical density is measured at 450 nm. The amount of complexes bound to the plate and the optical density is inversely proportional to the analyte concentration of the sample. Quantification of unknowns is achieved by comparing the enzymatic activity of unknowns with a response curve prepared by using known standards.

Test Procedure

1. Summary 1. Pipet 50 µl acylated standard, acylated control and acylated sample. 2. Add 50 µl Enzyme Conjugate. 3. Add 50 µl Antiserum and shake the plate carefully. 4. Cover plate and incubate 3 h at RT on a shaker. 5. Wash each well four times with 250 µl Wash Buffer. 6. Add 200 µl freshly prepared TMB Substrate Solution. 7. Cover plate and incubate plasma 40 min, urine 20 min at RT on a shaker. 8. Add 100 µl of TMB Stop Solution and mix gently. 9. Read OD at 450 nm within 60 min after stopping. 2. Detailed Instructions for Use Specimen Collection and Storage: for mor information refer to the chapter "alternative applications" Plasma The usual precautions for venipuncture should be observed. EDTA plasma should be used and can be stored at 2 - 8°C for up to 8 hours and should be frozen at -20°C or lower, if stored for longer periods. Avoid repeated freezing and thawing of samples. Urine The total volume of urine excreted during a 24 hour period should be collected and mixed in a single bottle containing 10 - 15 ml of 6 N hydrochloric acid as preservative. Exposure to direct sun light should be avoided. Urine samples which are not assayed immediately may be stored at -20°C or lower for at least 6 months. Avoid repeated freezing and thawing of samples. Cell Culture Supernatants (release from isolated mononuclear leukocytes) Cell culture supernatants may be used without special precautions except: Cell culture media may contain histamine! Store samples at -20°C. Whole Blood The histamine release is performed with heparinized whole blood. For further information see instructions for use of Histamine Release. Preparation of Reagents The contents of the kit can be divided into three separate runs. The volumes stated below are for one test procedure with 4 strips (32 determinations). If a larger number of strips is to be used, the volumes have to be changed accordingly. 1. Assay Buffer 20 ml of the Assay Buffer Concentrate have to be diluted 1:5 with bidist. water to make up 100 ml. The Assay Buffer is now ready for use. Store at 2 - 8°C. 2. Plasma Standards Add 0.4 ml bidist. water and wait for 15 min. Mix gently by swirling. Freeze aliquotes at < -20°C. 3. Control Plasma Add 0.4 ml bidist. water and wait for 15 min. Mix gently by swirling. Freeze aliquotes at < -20°C. 4. Wash Buffer 15 ml of the Wash Buffer Concentrate have to be diluted 1:20 with bidist. water to make up 300 ml. The Assay Buffer is now ready for use. Store at 2 - 8°C. Crystals may precipitate at 2 - 8°C. These crystals resolve at room temperature. 5. Enzyme Conjugate Dilute 10 µl of Enzyme Conjugate Concentrate in 2.0 ml of Assay Buffer (ready for use!). Prepare freshly for each test run! 6. TMB Substrate Solution (should be prepared during the test procedure) Dilute 300 µl of the TMB Substrate Concentrate with 9 ml of TMB Substrate Buffer and mix. Prepare just before use and use only once! Sample Preparation The reagents provided are sufficient for single determinations for sample preparation and duplicates for the ELISA. After removing assay reagents from the refrigerator, allow them to reach room temperature before pipetting. Unused reagents should be stored at 2 - 8°C. Sample preparation should be performed in glass tubes. 1. Plasma - Pipet 100 µl of each Plasma-Standards, Control Plasma and patient plasma into glass test tubes. - Add 100 µl of Indicator Buffer to each tube. - Add 20 µl of Acylation Reagent with a multipette to each tube, vortex mix and incubate for 30 min. at room temperature (20 - 25°C). - Add 0.75 ml ready for use Assay Buffer and vortex mix. 2. Urine and Cell Culture Supernatants (e. g. release from isolated basophilic leukocytes) - Pipet 50 µl of each U/Z Standards, Control Urine and patient urine or cell culture supernatants into glass test tubes. - Add 50 µl of Indicator Buffer to each tube. If the indicator becomes colourless, the pH of the solution is too low and the sample contained too much acid. In that case add another 50 µl ofIndicator Buffer until the solution remains reddish. - Add 10 µl Acylation Reagent with a multipette to each tube, vortex mix and incubate for 30 min. at room temperature (20 - 25°C). - Add 2 ml Assay Buffer and vortex mix. Assay Procedure After removing assay reagents from the refrigerator, allow them to reach room temperature before pipetting. Unused reagents should be stored at 2 - 8°C. Standards, controls and unknowns should be assayed in duplicate. Important: It is not possible to determine acylated urine or cell culture samples by use of the plasma-standard curve or to determine acylated plasma samples by use of urine/cell culture standard curve! Plasma and urine 1. Pipet 50 µl of each acylated standards, acylated controls and acylated samples into the appropriate wells. 2. Pipet 50 µl of Enzyme Conjugate (7.5.) and subsequently 50 µl of Antiserum with a multipette into each well, shake the plate carefully. 3. Seal the plate with the adhesive foil and incubate 3 hours at room temperature (20 - 25°C) on a shaker (500 rpm). 4. Wash each well four times with Wash Buffer, 250 µl per well (it is recommended to use a washer). Remove Wash Buffer carefully. Invert plate and remove any remaining liquid by tapping on clean blotting paper. Note: The correct performance of the washing procedure is mandatory for the sensitivity and precision of this assay. 5. Pipet 200 µl of freshly prepared Substrate Solution into each well. 6. Seal with the adhesive foil and incubate plasma for 40 min. at room temperature and urine for 20 min at room temperature on an orbital shaker (500 rpm). 7. Stop the substrate reaction by adding 100 µl of Stop Solution into each well. Mix contents briefly by shaking the plate gently. 8. Read the optical density at 450 nm (reference wave length 600 - 650nm) with a microtiter plate reader within 60 min. after stopping.

Performance Characteristics

1. Calculation of Results The concentration of the standards (abscissa, logarithmic) is plotted on a semilogarithmic graph paper against its corresponding optical density (ordinate, linear). The concentration of the samples can be read directly from this standard curve by using their average optical density. Alternatively, the optical density of each standard and sample can be related to the optical density of the zero standard, expressed as the ratio OD/OD max, and plotted on the ordinate. Shown below is a typical example of a standard curve with the Histamine ELISA. Concentration OD 1 OD 2 Mean value OD/ODmax C.V. (ng/ml) (OD) (%) (%) 0.0 1.883 1.884 1.884 100 0.0 0.67 1.574 1.572 1.573 83.5 0.1 2.0 1.395 1.457 1.426 75.7 3.1 6.0 1.060 1.146 1.103 58.6 5.5 18 0.719 0.689 0.704 37.4 3.0 54 0.345 0.345 0.345 18.3 0.0 162 0.145 0.139 0.142 7.5 3.0 2. Cross-reactivity The cross-reactivity of the anti-N-acylhistamine antiserum has been measured against various compounds which were processed like patient samples. The percent cross-reactivity is expressed as the ratio of histamine concentration to the concentration of the reacting compound at 50% binding of the 0 ng/ml standard. Compound Cross-reactivity (%) N-acylated histamine 100.0 N-methyl-histamine 2.42 N-acetyl-histamine 0.61 1-methyl-histamine 0.03 L-histidine 0.005 5-hydroxy-3-indole acetic acid 0.005 L--imidazole lactic acid 0.005 1-methy-4-imidazole acetic acid 0.005 imidazole-4 acetic acid 0.005 5-hydroxytryptamine 0.005 3. Sensitivity The lowest detectable level that can be distinguished from the zero standard is 2.4 ng/ml for urine and cell culture supernatants and 0.3 ng/ml for plasma samples (defined as 3 x standard deviation of the zero standard). 4. Precision Intra Assay Variation (in ng/ml) Specimen Mean SD CV % N Plasma 4.42 0.37 8.3 10 25.31 1.02 4.0 10 Urine 7.15 0.28 3.9 10 26.95 0.96 3.5 10 Inter Assay Variation (in ng/ml) Specimen Mean SD CV % N Plasma 4.21 0.34 8.1 11 22.62 1.57 6.9 11 Urine 7.67 0.60 7.8 11 28.90 1.77 6.1 11 5. Dilution Plasma Unknown patient samples were diluted with zero plasma before sample preparation and assayed. The calculated results are shown in ng/ml: Dilution undiluted 1/2 1/4 1/8 1/16 Plasma 1 10.9 10.6 10.7 10.2 12.0 Plasma 2 33.0 32.7 36.2 29.0 33.0 Plasma 3 10.7 12.6 12.0 9.5 13.9 Urine Unknown patient samples were diluted with U/Z Standard A before sample preparation and assayed. The calculated results are shown in ng/ml: Dilution undiluted 1/2 1/4 1/8 Urine 1 132.0 140.8 129.4 137.1 Urine 2 64.4 67.6 65.6 63.0 Urine 3 59.8 57.5 58.3 60.9 6. Recovery Human plasma was enriched with increasing amounts of histamine: (data in ng/ml) Plasma Sample Added Expected Observed Recovery (ng/ml) (ng/ml) (ng/ml) (%) Plasma 1 - - 1.27 - 3 4.27 5.05 118 9 10.27 10.70 104 27 28.27 31.02 109 81 82.27 83.03 101 Plasma 2 - - 0.20 - 3 3.20 3.29 103 9 9.20 9.69 105 27 27.20 27.49 101 81 81.20 83.75 103 Plasma 3 - - 0.81 - 9 9.81 10.27 105 27 27.81 26.02 94 81 81.81 75.31 92 The average recovery is 103% Urine Sample Added Expected Observed Recovery (ng/ml) (ng/ml) (ng/ml) (%) Urine 1 - - 22.16 - 1 23.16 24.45 106 3 25.16 23.98 95.3 9 31.16 31.24 100 27 49.16 48.24 98 81 103.16 103.71 101 Urine 2 - - 17.31 - 1 18.31 18.52 101 3 20.31 21.25 105 9 27.31 28.29 104 27 44.31 43.62 98 81 98.31 101.11 103 Urine 3 - - 8.11 - 1 9.11 10.24 112 3 11.11 12.37 111 9 17.11 17.78 104 The average recovery is 103%

Expected Values

It is recommended that each laboratory establishes its own range of normal histamine values. The following values may serve as a guide line: Plasma: 0.3 - 1.0 ng/ml Blood: 20 - 200 ng/ml Urine: 3 - 10 ng/ml 10 - 50 µg/d

Alternative Applications

Alternative Species resp. Specimen 1. Human Specimen: Test can be used for: Human Specimen | Applicable Yes/No | Expected Values ===============|===================|======================== Serum | No | Plasma/EDTA | Yes | < 1ng/ml | | Urine | Yes | 10-50µg/day Saliva | Not known | CSF | Not known | 2. Other Species (animals) Test can be used for: Species | Specimen | Expected Values =========|================|================== Cat | Plasma | Not known Horse | Plasma | Not known Rat | Bronchoalveo-| Histamine Release | lar lavage | | fluids **) | Rat | Plasma | Comparable to | | humans **) see paper in Nature employing the IBL kit. Not applicable to dogs. 3. Additional applications 3.1. Test can be used for cell culture supernatants with a special protocol included in the full instructions for use. 3.2. For the determination of Histamine in food see the IBL kit Histamine in foods (RE 59211). 3.3. Test applicable for the measurement of Histamine Release in heparinized whole blood after stimulation with specific allergens. For further details see the IBL protocol - RE 95000 -.

(More) Clinical Background

Clinical significance of histamine release Histamine is a potent mediator of numerous biological reactions. It is formed by the enzymatic decarboxylation of histidine, and therefore has to be considered as a biogenic amine. In the human organism it is virtually ubiquitous in tissues and body fluids, being mainly stored in its inactive form in the metachromatic granula of mast cells and basophilic leukocytes. On release, histamine functions as a potent mediator of numerous physiological and pathophysiological processes in nearly all organs and tissues. A possible role for histamine in immunological and inflammatory reactions has been concluded from its interactions with varios cytokines. Histamine has been clearly implicated as a primary mediator of "acute phase" allergic reactions. Its biological activities in tissues are mediated by three different cell surface receptors (i.e. H1, H2 and H3 receptors). Biological activities of histamine in man are dependent on plasma histamine levels: Histamine (ng/ml) | Biological activities -----------------------|------------------------------------ 0 - 1 | none 1 - 2 | enhanced gastric acid secretion 3 - 5 | Tachycardia, skin reactions 6 - 8 | decreased arterial pressure 7 - 12 | broncho-spasms approx. 100 | cardiac arrest For routine diagnosis the occurence of flushing should be assessed as a clinical indication of the need for histamine testing. Elevated histamine levels are found in cases of mastocytoma, chronic myeloid leukaemia (CML) and polycythaemia vera. The uncontrolled histamine release following the consumption of different foods (e.g. fish, cheese, yoghurt, sauerkraut as well as wine and champagne) may cause a dangerous histamine situation, especially in persons with allergies. Toxic side effects include circulatory disorders, headaches and gastro-intestinal pains and may lead to chronic intoxication and liver damage. ------------------------------------------------------------------------- Elias V. Balakas, Gerasimos I. Bamihas, Michaelis Karamouzis, George Voyiatzis, Achilleas Tourkantonis. Histamine and Serotonin in Uremic Pruritus: Effect of Ondansetron in CAPD-Pruritic Patients Nephron 78, 395 - 402 (1998) Pruritus is a common, unpleasant symptom of uremic patients. Serotonin and histamine have been reported as possible mediators of uremic pruritus, and ondansetron is a potent and selective inhibitor of 5-HT3 receptors. The aims of our study were (1) to evaluate the effect of ondansetron on uremic pruritus in continuous ambulatory peritoneal dialysis (CAPD) patients and its safety and (2) to investigate the role of histamine and serotonin in uremic pruritus. To study the prevalence and pathogenesis of uremic pruritus, CAPD and hemodialysis (HD) patients were asked to complete a pruritus questionnaire. The replies were scored based on numerical scales, and the results were evaluated by the same investigator who did not know the patients. Pruritus was graded, according to the total points for each patient, as mild, moderate, or severe. Of 54 patients on HD, 29 (53.7 %) had pruritus, and of 43 patients on CAPD, pruritus was present in 21 (48.8 %). In HD patients, pruritus was mild in 14 (48.3 %), moderate in 12 (41.4 %), and severe in 3 (10.3 %) patients; the distribution in CAPD patients was 9 (42.9 %), 10 (47.6 %), and 2 (9.5 %), respectively. There was no correlation between the presence and severity of pruritus and age, sex, primary renal disease, duration of dialysis, dialysis solutions used, and hematological and biochemical parameters except for serum histamine and serotonin levels and their product. Plasma histamine levels in CAPD patients were 13.1 ñ 1.1 ng/ml in pruritic and 11.0 ñ 3.9 ng/ml in nonpruritic patients (p = 0.06), serum serotonin levels were 115.6 ñ 43.3 ng/ml and 64 ñ 42.3 ng/ml (p < 0.05), respectively, and the histamine x serotonin product was 1,461 ñ 576 and 646 ñ 545 (p < 0.01), respectively. Eleven CAPD patients (6 males, 5 females) with a mean age of 66 (range 33- 83) years and an average time on CAPD of 18 (range 3-31) months with moderate to severe pruritus were treated with ondansetron (4 mg twice daily p.o.) for a mean period of 3 (range 1-5) months. All patients responded to the treatment. There was a significant reduction of the severity of pruritus from the start of treatment, and on the 3rd day the pruritic score (mean value) was 10 (range 5-19) points, while at time 0 (before treatment) it was 26 (range 19-37) points (p < 0.0001). Pruritus disappeared in 7 patients at the end of the 1st week and in all patients at the end of the 2nd week of treatment. This effect was maintained during the study. Plasma histamine levels decreased significantly during the treatment from 12.9 ¤ 1.2 to 6.7 ñ 5.9 ng/ml (p < 0.05). Also, serum serotonin levels were reduced from 125.1 ¤ 47.8 to 59.3 ñ 27.5 ng/ml (p < 0.05) at the end of the 1st month of treatment, and the histamine x serotonin product showed a more significant reduction: from 1,544 ñ 656 to 454 ñ 436 (p < 0.01). Three patients reported an improvement in their nausea and vomiting during the treatment. Weekly clinical and laboratory examinations showed no side effects, adverse reactions, or other complications. Our data indicate that ondansetron is an effective, safe, and well- tolerated drug for the treatment of uremic pruritus in CAPD patients and that histamine and serotonin may have a crucial role in the appearance or perception of the uremic pruritus.

Sales Arguments

Potential customers and indications The clinical indications are mainly in the diagnosis of hypertension and allergy testing (see Guide-line to Biogenic Amines). - private laboratories, universities, allergy centres, research centres, pharmaceutical industry e.g. testing of peptic ulcer drugs, testing of drugs in connection with management of wakefulness and sleep Customers are medium-sized laboratories, hospitals with more than 800 beds, researchers in labs included in hospitals. Arguments - Publication in: Nature Medicine Volume 2, Number 5, May 1996, 540-544 - ELISA kit applicable to plasma, urine and cell culture supernatants - Very short incubation time of only 3 hours at room temperature (total time about 4 hours) - Wide standard range of 0.67 - 162 ng/ml in plasma samples - Break apart strips for short assa runs - Ready to use liquid acylation reagent included in the kit - The lowest detectable level is 0.25 ng/ml - Very good correlation to RIA and GCMS - Easy handling due to the use of peroxidase labeled histamine (omission of one wash- and pipetting step in comparison to biotin version) - Low cross reactivity against N-methyl-histamine - Assay applicable to histamine measurement in different foodstuffs (see RE59211) - Assay applicable to histamine release testing of allergens within one day, or alternatively it is possible to freeze the supernatant - Only small sample volume for histamine release (applicable to children samples) Competitors - HPLC: very time-consuming, restricted to highly specialized laboratories General arguments HPLC vs. immunoassays: - After switching to immunoassays, the HPLC equipment may be used e.g. for therapeutic drug monitoring or for other analytes for which no routine test kits are available.

Product Literature

1. Product Literature References Hsu, C.-H., Chua, K.-Y., Tao, M.-H., Lai, Y.-L., Wu, H.-D., Huang, S.-K. & Hsieh, K.-H. (1996): Immunoprophylaxis of allergen-induced immunoglobulin E synthesis and airway hyperresponsiveness in vivo by genetic immunization. Nature Medicine, Vol. 2, No. 5: 540-544. Address: Kue-Hsiung Hsieh, Chang Gung Children`s Hospital, Taiwan, Republic of China 2. Other Literature References Histamine 1. Masini E et al. The role of histamine in platelet aggregation by physiological and immunological stimuli. Inflamm. Res., 47: 211-220 (1998) . 2. Balaskas EV, Bamihas GI, Karamouzis M, Voyiatzis G, Tourkantonis A. Histamine and serotonin in uremic pruritus: effect of ondansetron in CAPD-pruritic patients. Nephron, 78:395-402 (1998) 3. Karamouzis EV et al. Histamine and serotonin as markers of uremic pruritus. Clin. Chem., 43: S113 (1997) . 4. Neuber K et al. Staphylococcus aureus enterotoxins induce histamine and leukotriene release in patients with atopic eczema. In: New Trends in Allergy IV (Ring J, Behrendt H, Vieluf D), pp 223-227, Springer-Verlag Berlin Heidelberg 1997 5. Bruce C, Taylor WH. Plasmahistaminkonzentration bei Patienten mit Eosinophilie und akutem Asthma sowie Tropenkrankheiten. Clin. Chem., 11: 990 (1996) . 6. Hsu C-H et al. Immunoprophylaxis of allergen-induced immunoglobulin E synthesis and airway hyperresponsiveness in vivo by genetic immunization. Nature Medicine, 2: 540-544 (1996) 7. Dahl JB. Antihistamine prophylaxis and general anaesthesia. Lancet, 343: 929-930 (1994) 8. Hermann K et al. Contamination of heparin by histamine: measurement and characterization by high-performance liquid chromatography and radioimmunoassay. Allergy, 49: 596-572 (1994) 9. Audicana M et al. Allergic reactions to betalactams: studies in a group of patients allergic to penicillin and evaluation of cross-reactivity with cephalosprin. Allergy, 49: 108-113 (1994) 10.Prinz J. Immunologische Grundlagen allergischer Erkrankungen. Allergologie, 16: 126-133 (1993) 11.Falus A and Merétey K.Histamine: an early messenger in inflammatory and immune reactions. Immunol. Today, 13. 154-156 (1992) 12.Siraganian RP. Histamine secretion from mast cells and basophils. TIPS, 10: 432-437 (1983) 13.Myers G et al. Measurements of urinary histamine: development of methodology and normal values. J. Allergy Clin. Immunol., 67: 305-311 (1981) Histamine release 1. Petersen LJ et al. Studies on mast cells and histamine release in psoriasis: the effect of ranitidine. Acta Derm. Venereol., 78: 190-193 (1998) . 2. Duda D et al. Can clinically relevant histamine release be accurately diagnosed in anaesthetised patients without plasma histamine measurements? Randomised study with nested sampling aimed to change paradigms. Inflamm. Res., 47: 73-74 (1998) 3. Balaskas EV, Bamihas GI, Karamouzis M, Voyiatzis G, Tourkantonis A. Histamine and serotonin in uremic pruritus: effect of ondansetron in CAPD-pruritic patients. Nephron, 78:395-402 (1998) 4. Capulong MCT et al. Cold stimulation test and histamine release in primary acquired cold urticaria. Int . Arch. Allergy Immunol., 114: 400-403 (1997) 5. Sanz ML, Ferrer M, Prieto I, Oehling A. Sulphidoleukotriene and histamine releasability in atopic patients. Int. Arch. Allergy Immunol., 113: 305-306 (1997) 6. Lorenz W et al. Incidence and clinical importance of perioperative histamine release: randomised study of volume loading and antihistamines after induction of anaesthesia. Lancet, 343: 933-939 (1994) 7. Neugebauer E et al. Histamine release in sepsis: a prospective, controlled, clinical study. Crit. Care Med., 24: 1670-1677 (1996) 8. Suiyama H et al. Importance of interleukin-3 on histamine release from human basophils. Ann. Allergy, 71. 391-395 (1993) 9. Hsieh K-H et al. Histamine releasing factors - a review of their clinical significance. ACI News, 5: 42-46 (1993) 10.Koller DY et al. Assessment of histamine release from basophils in whole blood by benzylpenicilloyl poly-L-lysine in penicillin-sensitized patients. Allergy, 47: 459-462 (1992) 11.Stephan V et al. Determination of N-methylhistamine in urine as an indicator of histamine release in immediate allergic reactions. J. Allergy Clin. Immunol., 86: 862-868 (1990) 12.Griese M et al. Histamine release test in comparison to standard tests in diagnosis of childhood allergic asthma. Ann. Allergy, 65: 46-51 (1990) 13.Le Mao J et al. Relationship between specific circulating IgE, basophil cell-bound IgE and histamine release induced by purified allergens of Dermatophagoides farinae. Int Archs. Allergy appl. Immun., 76: 289-295 (1985) 14.Maasch HJ, Fischer B, Wahl R, Wahn U. Comparison of histamine release assay and RAST inhibition as tools for allergen extract standardization. Int. Archs. Allergy appl. Immun., 73: 314-320 (1984) 15.Maasch et al. Histamine release. In: Arbeiten aus dem Paul-Ehrlich Institut, dem Georg-Speyer-Haus und dem Ferdinand-Blum-Institut, 79: 145-154, Gustav Fischer Verlag Stuttgart NewYork (1984) 16.Wahn U, Maasch HJ, Geissler W. Leukocyte histamine release and humoral changes during oral and subcutaneous hyposensitization of grass pollen allergic children. Helv. paediat. Acta, 39: 137-144 (1984) 17.Lorenz W et al. Definition and classification of histamine-release response to drugs in anaesthesia and sugery: studies in the conscious human subject. Klin. Wochenschr., 60: 896-913 (1982)
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