This paper was aimed to establish screening methods of anaphylactoid reaction caused by safflower yellow for injection based on RBL-2 H3 cell degranulation model and mice model for acute anaphylactoid reaction,and evaluate the hypersensitivity caused by safflower yellow for injection from different batches. An in vitro cell model was used to keep the cells stimulated for an hour with different batches of safflower yellow for injection as the drug group,serum-free MEM medium as negative control group and 30 mg·L-1 C48/80 as positive control group respectively. The supernatant was then absorbed,and neutral red staining technique was used to detect the effect of safflower yellow injection on the degranulation of RBL-2 H3 cells with the positive cell rate of degranulation as the indicator.An in vivo model was established to validate the experimental results,and mice model for acute anaphylactoid reaction and ELISA method were adopted to detect the plasma histamine content,and screen the hypersensitivity caused by safflower yellow for injection at the animal level by using plasma histamine content as a test index. The results of the neutral red staining experiments showed that the positive control C48/80 could cause cell degranulation,and most of the cells were deeply stained. There was significant difference in positive cell rate between different batches of safflower yellow and positive control group. In the mice model for acute anaphylactoid reaction,it was found that the positive control C48/80 significantly increased the histamine content in the plasma of mice,while the safflower yellow in each batch did not cause a significant increase in plasma histamine( P<0. 000 1). The mechanism of anaphylactoid reaction is relatively complicated. This study was mainly based on the release of histamine and other active substances by degranulation of mast cells. No significant degranulation reaction of RBL-2 H3 cells induced by safflower yellow for injection was detected,nor was the plasma histamine level significantly increased in mice from the in vitro and in vivo aspects.
Anaphylaxis ; chemically induced ; Animals ; Cell Degranulation ; drug effects ; Cells, Cultured ; Chalcone ; adverse effects ; analogs & derivatives ; Histamine ; blood ; Mast Cells ; drug effects ; Mice

The detection of drug-induced anaphylactoid reactions remains a global challenge,still lacking mature and reliable animal models or test methods. Therefore,the purpose of this paper is to explore and establish the test methods and evaluation standards for anaphylactoid reactions that apply to injection drugs. Based on the anaphylactoid reaction symptoms of mice induced by intravenous injection drugs C48/40 and Tween 80,a list of systemic anaphylactoid reaction symptoms in mice was sorted out and an evaluation standard of anaphylactoid reactions symptoms was established by applying symptom intensity coefficient K( that can represent these verity of anaphylactoid reaction symptoms) and its calculation formula Accordingly,histamine,tryptase,and Ig E were selected as blood indicators of anaphylactoid reactions,so that a test method combining symptoms evaluation and blood makers detection was established.This test method could be used to evaluate the characteristics of anaphylactoid reactions: coefficient K,blood histamine levels were highly and positively correlated with C48/80 and Tween 80 dose; The log value of histamine was highly and positively correlated with K; tryptase level may rise,or remain steady,or drop,possibly associated with the characteristics of the tested object and time for blood taking; and Ig E level would drop or remain steady,but it would not rise,which can be clearly distinguished from type I allergic reactions. On this basis,tiohexol,iopromide,paclitaxel,Xuesaitong Injection,Shuanghuanglian Injection and Shengmai Injection were used to investigate the applicability. The testing results showed a high degree of consistency with the actual clinical situation. The results suggest that the method of systemic anaphylaxis test in mice has high sensitivity,specificity and good consistency with clinical practice.It is suggested to be further validated and popularized.
Anaphylaxis ; chemically induced ; diagnosis ; Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; toxicity ; Histamine ; blood ; Immunoglobulin E ; blood ; Injections, Intravenous ; Mice ; Shock ; chemically induced ; diagnosis ; Toxicity Tests ; Tryptases ; blood

OBJECTIVE: To investigate the incidence of peri-anesthesia allergy in a tertiary teaching hospital. METHODS: This was a retrospective cohort study. Patients who received anesthesia in operation rooms at Peking University First Hospital from January 2012 to April 2017 were enrolled. Researchers reviewed all the patients' electronic records and screened suspect allergy cases. Allergy was diagnosed according to the definition in Consensus on Management of Perioperative Allergy (China) and Scandinavian Clinical Practice Guidelines on the Diagnosis, Management and Follow-up of Anaphylaxis during Anesthesia. After obtaining the electronic records, two researchers began to screen and supplement missing data according medical records independently, then they checked out each other's data. The final data were reviewed by another two researchers. We collected the patients' basic characteristics, surgery type, anesthesia type, peri-anesthesia use of drugs, prognosis and other data. Univariate logistic regression was employed to screen potential factors of allergy. Factors with statistical significance (P<0.05) in univariate Logistic regression were entered into multivariate Logistic regression to identify independent risk factors of allergy. RESULTS: In the study, 106 074 patients entered final statistic analysis. The incidence of peri-anesthesia allergy was about 1.5/1 000 (156/106 074). The incidence of Grades I, II and III allergy was 64.1% (100/156), 30.1% (47/156), and 5.8% (9/156) respectively. Multivariate logistic regression showed 5 independent risk factors of allergy including history of allergy (OR=6.836, 95%CI: 4.461-10.474, P<0.001), intraoperative use of sufentanil (OR=1.993, 95%CI: 1.228-3.232, P=0.005), intraoperative use of cis-atracuronium (OR=2.495, 95%CI: 1.599-3.893, P<0.001), intraoperative infusion of antibiotics (OR=2.005, 95%CI: 1.375-2.924, P<0.001) and frozen fresh plasma (OR=3.055, 95%CI: 1.842-5.068, P<0.001). CONCLUSION The incidence of peri-anesthesia allergy is high and further attempt is needed to establish standard operation process of diagnosis and treatment of allergy.
Anaphylaxis/chemically induced* ; Anesthesia ; Anesthetics/adverse effects* ; China ; Drug Hypersensitivity ; Humans ; Retrospective Studies ; Risk Factors ; Surveys and Questionnaires

Anaphylaxis ; chemically induced ; diagnosis ; Anti-Infective Agents, Local ; adverse effects ; Chlorhexidine ; adverse effects ; Humans ; Male ; Middle Aged

Acute Disease ; Anaphylaxis ; drug therapy ; Epinephrine ; administration & dosage ; adverse effects ; therapeutic use ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; diagnosis ; etiology ; Thrombosis ; chemically induced ; complications

Because of the rapid action and high bioavailability, traditional Chinese medicine injections (TCMIs) had been widely used in clinical critical field. In recent years, with the increasing reports of clinical adverse reaction, more and more attention was paid to them, and acute allergic reaction was the main adverse reaction. Acute allergic reaction included type-I anaphylaxis reaction and anaphylactoid reaction, the latter had been found in a variety of TCMIs and accounted for 77% of adverse reaction. But the mechanism of anaphylactoid reaction was not completely understood, the standard animal model for TCMIs was not established, and the technical guidance for anaphylactoid reaction was not formulated. Thus the three aspects included mechanism, evaluation index and evaluation methods of TCMIs for anaphylactoid were reviewed. Five ways including direct stimulating pathway, complement pathway, coagulation pathway, kallikrein-kinin pathway and acute allergic pathway were the main mechanism of anaphylactoid reaction; whole animal model and cell model were the main evaluation methods; the occurrence index and effect index were reviewed for the evaluation index analysis.
Anaphylaxis ; chemically induced ; Animals ; Drug Hypersensitivity ; diagnosis ; etiology ; Humans ; Injections ; Medicine, Chinese Traditional ; adverse effects

The experiment is designed to explore pathological festures and material basis of pseadoanaphylactoid reaction induced by notoginseng total saponin preparation. Mouse pseadoanaphylactoid reaction was used, 50 ICR mice were randomly assigned to control group, positive medicine group, notoginseng total saponin preparation low-dose group, notoginseng total saponin preparation middle-dose group, notoginseng total saponin preparation high-dose group on average. They are treated by intravenous injection of test substance solutions containing 0.4% Evans blue (EB). 30 min later, scores of ear blue staining and quantitation of ear EB exudation were recorded. Another two experiment were repeated in the same way excluding EB, just to. detect the related cytokines in serum using ELISA. We found that the scores of pseudoanaphylactoid reaction in notoginseng total saponin preparation injection middle-dose group and high-dose group was evidently higher than that in control group, suggesting that notoginseng total saponin preparation injection may be can lead to pseadoanaphylactoid reaction. HE staining showed that pseadoanaphylactoid reaction induced by notoginseng total saponin preparation injection is related to inflammation. Histamine, VEGF and TNF-α levels in notoginseng total saponin preparation middle-dose group and high-dose group significantly increased (P < 0.05, P < 0.01) than control group and showed a dose-dependent manner as well as consistent with the degree of ear blue dye. While IL-6 and IL-10 content did not increase significantly in notoginseng total saponin preparation low-dose group and middle-dose group, but they significantly higher than control group (P < 0.05, P < 0.01) when it increased to quadrupe clinical concentrations, eight times of the clinical dose. So pseadoanaphylactoid reaction caused by notoginseng total saponin preparation may be related to histamine, VEGF, TNF-α, and it is possible that IL-6 and IL-10 can play a role when pseadoanaphylactoid reaction achieve a certain high degree.
Anaphylaxis ; chemically induced ; Animals ; Capillary Permeability ; drug effects ; Cytokines ; blood ; Dose-Response Relationship, Drug ; Drug Hypersensitivity ; etiology ; Mice ; Mice, Inbred ICR ; Panax notoginseng ; adverse effects ; chemistry ; Saponins ; adverse effects

Both immediate and delayed hypersensitivity reactions to iodinated contrast media (ICM) are relatively common. However, there are few data to determine the clinical utility of immunologic evaluation of ICM. To evaluate the utility of ICM skin testing in patients with ICM hypersensitivity, 23 patients (17 immediate and 6 delayed reactions) were enrolled from 3 university hospitals in Korea. With 6 commonly used ICM including iopromide, iohexol, ioversol, iomeprol, iopamidol and iodixanol, skin prick (SPT), intradermal (IDT) and patch tests were performed. Of 10 patients with anaphylaxis, 3 (30.0%) and 6 (60.0%) were positive respectively on SPTs and IDTs with the culprit ICM. Three of 6 patients with urticaria showed positive IDTs. In total, 11 (64.7%) had positive on either SPT or IDT. Three of 6 patients with delayed rashes had positive response to patch test and/or delayed IDT. Among 5 patients (3 anaphylaxis, 1 urticaria and 1 delayed rash) taken subsequent radiological examinations, 3 patients administered safe alternatives according to the results of skin testing had no adverse reaction. However, anaphylaxis developed in the other 2 patients administered the culprit ICM again. With 64.7% (11/17) and 50% (3/6) of the sensitivities of corresponding allergic skin tests with culprit ICM for immediate and delayed hypersensitivity reactions, the present study suggests that skin tests is useful for the diagnosis of ICM hypersensitivity and for selecting safe ICM and preventing a recurrence of anaphylaxis caused by the same ICM.
Anaphylaxis/chemically induced/diagnosis/immunology ; Contrast Media/*adverse effects ; Cross Reactions/immunology ; Dermatitis, Contact/*diagnosis/*immunology ; Drug Hypersensitivity/diagnosis ; Female ; Humans ; Iodides/*immunology ; Iohexol/analogs & derivatives ; Iopamidol/analogs & derivatives ; Male ; Middle Aged ; Republic of Korea ; Skin Tests/*methods ; Triiodobenzoic Acids ; Urticaria/diagnosis/immunology

PURPOSE: Cefaclor is widely prescribed for various infectious diseases. As its consumption increases, the number of hypersensitivity reactions to cefaclor has increased. This study aimed to evaluate the immunologic findings of immediate hypersensitivity to cefaclor. MATERIALS AND METHODS: We enrolled 47 patients with immediate hypersensitivity to cefaclor from Ajou University Hospital and Asan Medical Center. Serum specific IgE, IgG1, and IgG4 antibodies to cefaclor-human serum albumin (HSA) conjugate were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The most common phenotype was anaphylaxis (Group I, 78.7%), followed by urticaria (Group II, 21.3%). The detection of specific IgE, IgG1, and IgG4 to cefaclor-HSA conjugate by ELISA tended to be higher in Group I (40.5%, 41.7%, 21.6%) than in Group II (20.0%, 20.0%, 0%) with no statistical significance. Significant associations were found between specific IgE and IgG1 or IgG4 (p<0.001, p=0.019). ELISA inhibition tests showed significant inhibitions by both free cefaclor and cefaclor-HSA conjugate. For basophil activation tests in patients having no specific IgE antibody, the CD63 expression level on basophils increased with incubations of free cefaclor. CONCLUSION: The most common manifestation of immediate hypersensitivity to cefaclor was anaphylaxis, most of which was mediated by IgE; however, a non-IgE mediated direct basophil activation mechanism was suggested in a subset of anaphylaxis patients.
Adolescent ; Adult ; Aged ; Anaphylaxis/*chemically induced/immunology ; Anti-Bacterial Agents/adverse effects/*immunology ; Antigens, CD63 ; Basophils/metabolism ; Cefaclor/*adverse effects/immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Hypersensitivity, Immediate/chemically induced/diagnosis/*immunology ; Immunoglobulin E/*blood ; Immunoglobulin G/immunology ; Male ; Middle Aged ; Retrospective Studies ; Skin Tests ; Urticaria/chemically induced/diagnosis/immunology ; Young Adult

We experienced a case of immunoglobulin E (IgE) mediated anaphylaxis to levodropropizine. The patient was an 18-year old Korean woman. After taking the common cold medication including acetaminophen, domperidone, and levodropropizine, skin rash, angioedema and anaphylaxis were developed immediately. As she was tolerable to acetaminophen alone, we thought the culprit agent was maybe a levodropropizine tablet. To confirm the culprit, she underwent skin prick test and oral drug provocation test with the suspected one. Finally we detected levodropropizine specific IgE and confirmed the specificity by inhibition enzyme-linked immunosorbent assay (ELISA).
Adolescent ; Anaphylaxis/*chemically induced/*immunology ; Antitussive Agents/*adverse effects ; Bronchial Provocation Tests ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunoglobulin E/*immunology ; Propylene Glycols/*adverse effects ; Skin Tests