Effects and mechanism of anaphylactoid reaction induced by nonapeptide activating mast cells / 中国药房

OBJECTIVE To study the effects and potential mechanism of anaphylactoid reaction induced by nonapeptide IVQKIKHCF activating mast cells. METHODS Using human mast cell line LAD2 as subject， and substance P as positive control， the activation effects of 25， 50 and 100 μmol/L IVQKIKHCF on mast cells were investigated by determining the release rate of β-aminohexosidase， histamine release， and the contents of inflammatory factors； using MrgprX2-knockdown LAD2 cells and Mas- related G protein-coupled receptor X2 （MRGPRX2） high-expression human embryonic kidney cell line HEK293 （MRGPRX2/ HEK293 cells） as subject， the correlation between the activation effect of IVQKIKHCF and MRGPRX2 was investigated by determining the release rate of β-aminohexosidase， and intracellular calcium ion concentration. RESULTS IVQKIKHCF with 25， 50， 100 μmol/L could significantly increase the release rate of β-aminohexosidase and histamine release in LAD2 cells （P＜0.05）， and promote the release of tumor necrosis factor-α， interleukin-8， macrophage inflammatory protein-1β and monocyte chemotactic protein-1 to varying degrees （P＜0.05）. After knocking down MrgprX2， the effects of 25， 50， 100 μmol/L IVQKIKHCF promoting the release of β-aminohexosidase in LAD2 cells were reversed significantly （P＜0.05）， resulting in an increase of calcium ion concentration in MRGPRX2/HEK293 cells. CONCLUSIONS Nonapeptide IVQKIKHCF can promote mast cells to release granular matter and inflammatory mediators by activating MRGPRX2 thus inducing anaphylactoid reaction.

Establishment of new evaluation standards for systemic anaphylactoid reactions using mouse model / 中国中药杂志

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.

A high content screening method for detection of anaphylactoid reaction of injection formulations / 中国中药杂志

Anaphylactoid reaction (AR) is the most common adverse reaction of injection formulations, however, there are obvious drawbacks in available methods for AR detection. A novel in vitro detection method for AR was established based on fluorescent labeling and high content screen (HCS) system in present study. With the use of RBL-2H3 cells degranulation model, positive cell count was determined with specific cellular membrane fluorescent dye FM4-64 labeling vesicle recycle, and total cells count was determined with specific nucleus fluorescent dye Hochest 3334, and then the ratio of cells degranulation after drug stimulation was calculated. In order to verify the reliability of this HCS method, positive drug Compound 48/80 was first used to confirm the consistence of HCS method with the traditional β-hexosaminidase release test and the Evans blue staining ears test in mice. The results showed high consistence between HCS method and traditional testing methods, and the HCS method showed higher sensitivity than the other two tests. Then 30 samples of Danhong injection (DHI) with clinical allergy symptoms further were used to confirm the reliability of this HCS method. The HCS results showed high consistence with the clinical report, and the HCS method had the advantage in reducing the interference by drug color. Therefore, this HCS method is reliable, sensitive, simple and high-throughput method in detection of AR, applicable for the AR evaluation of injection formulations, and can provide guidance for safety of clinical application in clinical practice.

Pseudoallergic reactions of traditional chinese medicine injections and the approaches for risk prevention and control / 中国药学杂志

Allergic hypersensitivity reactions (AHRs) are the most commonly reported adverse reactions of traditional Chinese medicine injections, mainly including skin and mucosa redness, itching, abdominal pain, chest tightness, dyspnea and nausea, blood pressure decline, with clinical symptoms, and even shock or death. In this paper, we analyzed the characteristics of clinical adverse reactions and preclinical study results of traditional Chinese medicine injections, and proposed a view of point that the main adverse reactions of traditional Chinese medicine injections are nonallergic hypersensitivity reactions (NHRs) or pseudoallergic reactions (PARs) instead of real AHRs. Because there are absolute differences in the characteristics and the pathogenesis mechanisms between PARs and AHRs, they should not be confused, otherwise, the clinical processing measures and the direction of basic research on the adverse reactions of traditional Chinese medicine injections would be misleading. This paper also discussed the approaches for risk prevention and control of PARs of traditional Chinese medicine injections.

Study on Anaphylactoid Reaction Induced by Shuanghuanglian Injection / 中国中医药信息杂志

Objective To observe the anaphylactoid reactions of Shuanghuanglian injection, determine the serum histamine level of sensitized animal, and to investigate its correlation with anaphylactoid reactions.Methods The guinea pigs were randomly selected to observe the anaphylactoid reactions using Shuanghuanglian injections in the different injection speed or different doses, and the serum histamine and the serum IgE of sensitized animals were determined by ELISA. Results The anaphylactoid reactions were induced by Shuanghuanglian injections in the different conditions of injection speed and doses in guinea pigs. There were no obvious difference about the serum IgE level between Shuanghuanglian group and saline group were injected in injection speed and doses. The serum histamine level was significantly increased in Shuanghuanglian group both different conditions of injection speed and doses, and it related to doses and speed. Conclusion Shuanghuanglian injection can cause anaphylactoid reactions in guinea pigs, and the changes of serum histamine level are related to injection speed and doses of Shuanghuanglian injection.

Studies on Anaphylactoid Reactions Induced by Traditional Chinese Medicine Injections of Qingkailing and Xuesaitong / 中国中医药信息杂志

Objective To study anaphylactoid reactions induced by traditional Chinese medicine injections (TCMI) of Qingkailing (QKL) and Xuesaitong (XST) with RBL-2H3 cells;To provide some reference for improving the screening system of TCMI induced anaphylactoid reactions.Methods The IC50 induced by QKL and XST injections was determined by MTT assay. RBL-2H3 cells were stimulated with TCMI at different concentrations or with C48/80 or culture medium. Thirty minutes later, the supernatant was collected to determine the release of histamine andβ-hexosaminidase. The cell degranulation rate and the ultrastructure changes were observed. The ICR mice were given single injection of TCMI containing Evans Blue through tail vein. The number of the animal with blue ear, the total number of blue ears and the quantity of Evans Blue of extravasation were determined 30 minutes later.Results The IC50 of both QKL injection and XST injection was 12.5μL/mL. These two injections promoted RBL-2H3 cells to release histamine andβ-hexosaminidase at higher concentrations (P<0.05,P<0.01) in a dose dependent manner. Cell morphology showed a decrease of villous on the cell surface and an increase of the internal vacuolated structure. Both injections caused the blue ears of all animal with a rate of 100%. The quantity of Evans Blue of the extravasation was significantly increased (P<0.01). The results in vitro study were in close agreement with that in vivo.Conclusion Both QKL injection and XST injection may potentially cause anaphylactoid reactions. The RBL-2H3 cell model may be valuable to evaluate the anaphylactoid reactions induced by TCMI.

Methodological and Applicability Study of Rat Skin Anaphylactoid Test / 中国中医药信息杂志

Objective To study the sensitivity and reliability of rat skin anaphylactoid test method, detect and evaluate the anaphylactoid reaction of traditional Chinese medecine injection. Methods The condition of rat skin anaphylactoid test was optimized by studying the influencing factors of sensitivity and reliability of test with C48/80 as a tool drug, Tween80, endotoxin, China cobra toxin, trichosanthin injection, Tanreqing injection and Xuesaitong injection were investigated. Results The best conditions of rat skin anaphylactoid test was as follows:intrademal inject the drug with insulin syringe, 50-100μL per point, immediately inject 0.5%Evans blue dye 1 mL though caudal vein, 15 min later, kill the rat by carotid artery bleeding, clip dorsal skin to do the test. With this method, Tween80, endotoxin, China cobra toxin and trichosanthin injection all can induce blue stain in rat skin. Tanreqing injection showed no blue stain at the clinical dose. Xuesaitong injection although can induce blue stain in rat skin at the clinical dose, but the results cannot exclude the interference of its pharmacological function. Conclusion The method is simple with short test cycle, less dose of test drug, high detection sensitivity and good reproducibility, but some drug can show false positive result due to its own property.

Replacing solubilizer with lipid microspheres eliminates the severe adverse reaction of vitamin K1 injection / 中国药学杂志

OBJECTIVE: To investigate whether substituting the solubilizer with lipid microspheres in vitamin K1 injection can eliminate the anaphylactoid reaction.

Allergic Reaction Following Insertion of Vancomycin Loaded in Bone Cement

Vancomycin bead is an important ancillary treatment for osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA). However, red-man syndrome, which can be a life-threatening complication of vancomycin, may occur from the use of vancomycin beads albeit rarely. We report our first case of red-man syndrome caused by vancomycin bead's insertion for chronic osteomyelitis. Symptomatic treatment was not effective and removal of the vancomycin beads seems to be the best treatment for this condition.

Antidote for acetaminophen poisoning: N-acetylcysteine

N-acetylcysteine (NAC) is widely recognized as the antidote of choice for acetaminophen overdose. Acetaminophen is a commonly used analgesic and antipyretic agent, and its use is one of the most common causes of poisoning worldwide. Acetaminophen toxicity may occur acutely when supratherapeutic amounts are ingested purposefully or unintentionally. Liver failure may occur in severe toxicity. However, if treated early, patients with acetaminophen poisoning generally recover uneventfully. Acetaminophen is metabolized to N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified by conjugation with glutathione. In overdose, hepatic stores of glutathione are depleted and NAPQI binding to hepatocytes induces cell death and hepatic necrosis. NAC replenishes hepatic glutathione and may also act as a glutathione substitute, combining directly with the toxic metabolite. Intravenous NAC is indicated in patients who present with a history of acetaminophen overdose within the previous 8 to 10 hours, patients unable to tolerate oral NAC, and patients who present with evidence of fulminant hepatic failure. However, caution should be used in patients who have experienced previous hypersensitivity or anaphylactoid reactions to intravenous NAC, as well as in patients with asthma. The most common anaphylactoid reactions include rash, flushing, and bronchospasm. Adults should receive 150 mg/kg administered for 45 minutes, followed by 50 mg/kg administered for 4 hours, followed by 100 mg/kg administered for 16 hours. The total dose is 300 mg/kg delivered over 21 hours. Additionally, caution should always be used when intravenous NAC is prescribed and the amount of diluent is calculated. Monitoring of patients with a should include repeated neurologic and hemodynamic assessment.

Rocuronium bromide induced anaphylaxis in a child: A case report / 대한마취과학회지

Anaphylaxis or anaphylactoid reaction in pediatric patient during anesthesia is rare. We report a rocuronium induced anaphylactic reaction in a 33-month-old female. The patient was scheduled to undergo escharectomy due to injuries suffered from a major burn. Shortly after administration of rocuronium, the patient developed severe hypotension, tachycardia, and hypoxia. A similar reaction occurred after administration of rocuronium on subsequent anesthesia. She underwent uneventful anesthesia with volatile induction and maintenance of anesthesia with sevoflurane on her next 7 operations without using of muscle relaxant.

Inhibitory effects of curcumin on passive cutaneous anaphylactoid response and compound 48/80-induced mast cell activation / 대한해부학회지

Mast cells participate in allergies and inflammation by secreting a variety of pro-inflammatory mediators. Curcumin, the active component of turmeric, is a polyphenolic phytochemical with anti-tumor, anti-inflammatory, anti-oxidative, and anti-allergic properties. The effects of curcumin on compound 48/80-induced mast cell activation and passive cutaneous anaphylactoid reactions are unknown. In this report, we investigated the influences of curcumin on the passive cutaneous anaphylactoid response in vivo and compound 48/80-induced mast cell activation in vitro. The mechanism of action was examined by calcium uptake measurements and cAMP assays in mast cells. Curcumin significantly attenuated the mast cell-mediated passive cutaneous anaphylactoid reaction in an animal model. In agreement with this in vivo activity, curcumin suppressed compound 48/80-induced rat peritoneal mast cell (RPMC) degranulation and histamine release from RPMCs. Moreover, compound 48/80-elicited calcium uptake into RPMCs was reduced in a dose-dependent manner by curcumin. Furthermore, curcumin increased the level of intracellular cAMP and significantly inhibited the compound 48/80-induced reduction of cAMP in RPMCs. These results corroborate the finding that curcumin may have anti-allergic activity.

Life-Threatening Anaphylactoid Reaction in an Acute Ischemic Stroke Patient With Intravenous rt-PA Thrombolysis, Followed by Successful Intra-Arterial Thrombolysis

An anaphylactoid reaction to recombinant tissue plasminogen activator (rt-PA) is an uncommon but fatal complication. A 39-year-old man was admitted within 1 hour of the onset of a right hemispheric stroke. He was not taking any specific medication, including angiotensin-converting enzyme (ACE) inhibitors. A systemic anaphylactoid reaction developed immediately after rt-PA infusion. However, the symptoms were improved after treatment with a steroid and antihistamine. Subsequent intra-arterial thrombolytic therapy resulted in complete recanalization and clinical improvement. To our knowledge, this is the first report of a life-threatening anaphylactoid reaction after rt-PA treatment followed by successful intra-arterial thrombolytic therapy in a patient who had not taken an ACE inhibitor.

Anaphylaxis by atracurium on a cardiac surgery patient: A case report / 대한마취과학회지

Effective treatment of hypotension during induction of general anesthesia depends onhow well the many causes of the hypotension are understood. However, differential diagnosis of hypotension is by no means easy, especially when the prevalenceof hypotension is low or when the patient is asymptomatic. A 75 year-old female, upon induction of general anesthesia for open thoracic surgery, became hypotensive and showed generalized erythematous papules, therefore having to postpone the surgery. Upon further evaluation through skin prick tests, the hypotensive event was concluded to be caused by anaphylactic side effects of atracurium. Hence, atracurium was avoided and the surgery was successfully performed.

Pulseless Electrical Activity of Unknown Origin during Total Gastrectomy: A case report / 대한마취과학회지

Pulseless electrical activity refers to a heterogeneous group of cardiac rhythm disorders, all characterized by pulselessness in the presence of some type of electrical activity other than ventricular tachycardia or ventricular fibrillation. We experienced a case of sudden pulseless electrical activity and cardiac arrest during hetastarch infusion in general anesthesia in an adult who had total gastrectomy. We report this experience with a brief review of literature.

Anaphylactic Shock by Hemocoagulase with Increased Concentration of Mast Cell Tryptase: A case report / 대한마취과학회지

Multiple agents can cause anaphylaxis in a perioperative setting. Identifying the agent responsible is essential for avoiding future adverse reactions as well as to attenuate the progression of anaphylaxis. Being able to distinguish an anaphylactic reaction from an anaphylactoid reaction would help clarify the therapeutic and medicolegal issues. Anaphylaxis generally occurs after reexposure to a specific antigen and requires the release of proinflammatory mediators from mast cells and basophils. An increased concentration of mast cell tryptase is a highly sensitive indicator of anaphylactic reactions during anesthesia. Botropase(R) is a procoagulant hemocoagulase purified from venom of Bothrops jararaca, a Brazilian viper and in wide use in patients with high risk of bleeding. We report a case of suspected anaphylaxis to Botropase(R) in a 67 years old female patient undergoing segmental resection of the liver with elevated concentration of serum mast cell tryptase.

Intraoperative Anaphylactoid Reaction Due to Aprotinin during Pediatric Open Heart Surgery / 대한마취과학회지

Aprotinin is a serine protease inhibitor that improves the hemostatic function and modulates the anti-inflammatory responses. Recently, aprotinin has been widely used in various surgical procedures including open heart surgery. One of the complications of aprotinin is anaphylactic reaction and the incidence increases with re-exposure. We experienced a case of anaphylactic reaction in a 5-year-old female during open heart surgery. After cardiopulmonary bypass weaning, during aprotinin i.v. infusion for reducing blood loss, sudden hypotension and bradycardia occurred. After re-institution of CPB, the patient recovered. In the post-operative review of the chart and patient, we found that this patient had been exposed to aprotinin 20 days ago. In conclusion, we recommend some preventable methods for anaphylaxis of aprotinin; aprotinin should be used after a skin test or i.v. infusion test and used by mixing with CPB priming solution.

A Case of Intraoperative Cardiac Arrest due to Anaphylactoid Reaction: A case report / 대한마취과학회지

A number of drug administered during anesthesia can provoke pathologic response by immunologic or nonimmunologic mechanisms. Known drugs involved in hypersensitivity reactions are muscle relaxants, local anesthetics, narcotics, barbiturates, contrast media, protamine and antibiotics. Clinical manifestations of anaphylaxis are diverse, but during anesthesia, cardiovascular collapse is predominate. We experienced a case of anaphylactoid reaction with erythema on upper thoracic region, severe hypotension, tachycardia and ventricular fibrillation. After defibrillation, the patient was recovered. During follow-up, we knew that this patient was exposed aprotinin repeatedly, and suspect the possibility of anaphylactoid reaction due to aprotinin.

Anaphylactoid Reactions after Thrombokinase Administration: Two cases / 대한마취과학회지

The incidence of life-threatening anaphylactoid reactions during anesthesia has been increasing. Specific allergic reactions during anesthesia are usually due to muscle relaxants, barbiturates, local anesthetics, narcotics, radiocontrast media, antibiotics, and colloids. Thrombokinase, a hemostatic agent, has been used widely in clinical practice and severe anaphylactoid reactions to thrombokinase can occur rarely. We experienced two cases of anaphylactoid reactions after thrombokinase administration.

Anaphylactoid Reaction to Atracurium / 대한마취과학회지

A case is reported of anaphylactoid reaction to atracurium, used for the induetion of an- esthesia for skin graft in a 36 year old man. The patient had no previous history of any allergic tendency. It is not possible to distinguish between direct pharmacological effects and immune mediated hypersensitivity reactions by clinical observation alone. The mechanism of reaction in this patient was investigated by the leukocyte histamine release test, intradermal test, direct intravenous challenge with other induction agents used during the induction of anesthesia and radioallergosorbent test. The histamine releasing property of atracurium, the distinguishing methods between ana phylactic and anaphylatoid reaction, and the anesthetic management for this kind of reaction are discussed.