OBJECTIVETo observe the anaphylaxis and hemocytolysis of 6 kinds of tween-80 injection from different source.

METHODThe Hartley albinism guinea pig was used to carry on the active systematic anaphylaxis (ASA) and the passive cutaneous anaphylaxis (PCA). The in vitro hemolytic experiment and the hemocytolysis was observed by means of spectrophotometry on the domestic rabbit.

RESULTThe result of ASA and PLA of 6 kinds of tween-80 injection from different source assumed the negative. In observation time, the temolysis rate of 3 kinds of tween-80 injection are more than 5%, while the others are also more than 5% only in the highly concentrated test tube.

CONCLUSIONSix kinds of tween-80 injection from different source have not caused the immune-mediated anaphylaxis, but it may have hematolysis tendency on intravenous injection. The hemocytolysis of tween-80 may not be entirely caused by the impurities. It is worthy of further study that the physical and chemical properties of the product itself and the undeserved concentration is doubtful whether there is also some internal relations with the generation of hemolytic.

Anaphylaxis ; chemically induced ; Animals ; Chemistry, Pharmaceutical ; Female ; Guinea Pigs ; Hemolysis ; drug effects ; Injections ; Male ; Passive Cutaneous Anaphylaxis ; drug effects ; Polysorbates ; administration & dosage ; adverse effects ; chemistry ; Rabbits

OBJECTIVETo investigate allergic reactions of traditional Chinese medicine (TCM) injections, and to determine the contents of serum IgE and histamine in sensitized animal. The correlation between the preceding contents in serum and allergic reactions may be found, thus offering experimental evidences for advancing the accuracy of anticipation by type I allergy.

METHODWe carried out passive cutaneous anaphylaxis (PCA) tests,active systemic anaphylaxis (ASA) tests and anaphylactoid reactions using three TCM injections, and determined the contents of serum OVA-sIgE, total serum IgE and histamine in sensitized animals by ELISA method.

RESULTThe results of PCA test were negative, and there was no significant difference for total serum IgE level between experimental group and normal saline group. In the study of adjuvant effect in TCM injections + OVA (at the dose level that doesn't cause allergic reactions), the PCA results of SHL and YXC were positive and there was a increase in content of serum OVA-sIgE, while the PCA result of QKL was negative with a unobvious increase in the content of serum OVA-sIgE. The content of total serum IgE wasn't remarkably increased in each group and the results of ASA test were all positive. Three injections all caused anaphylactoid symptoms in guinea pigs in different doses or injection speed and the response intensity was found to be dosage and injection speed dependant. Furthermore, there was no significant difference for the content of total serum IgE in each group, whereas serum histamine concentration in every experimental group was markedly higher than normal saline group.

CONCLUSIONSHL and YXC increase the sensitivity of guinea pigs on OVA, and three TCM injections can cause allergic reactions in guinea pig. Allergic reactions of three TCM injections are correlated with specific IgE antibodies and histamine contents.

Animals ; Female ; Guinea Pigs ; Histamine ; blood ; Hypersensitivity ; drug therapy ; Immunoglobulin E ; blood ; Injections ; Male ; Medicine, Chinese Traditional ; Ovalbumin ; immunology ; Passive Cutaneous Anaphylaxis ; drug effects

OBJECTIVETo investigate the immunological mechanism of allergic dermatitis induced by trichloroethylene (TCE).

METHODSThe guinea pig model of TCE-induced allergic dermatitis was established by Guinea pig Maximization Test. The effects of TCE and its metabolites on splenic lymphocytes of TCE-sensitized and non-sensitized guinea pig were detected by MTT assay.

RESULTSFor TCE-sensitized guinea pig, the survival rate of lymphocytes cultured with TCE (+S9) was significantly higher than that cultured with TCE (-S9) (83.0% +/- 3.4% vs 75.9% +/- 7.9%, P < 0.01), while, for normal animals, the survival rate of lymphocytes cultured with TCE (+S9) was significantly lower than that cultured with TCE (-S9) (63.4% +/- 8.4% vs 77.0% +/- 7.2%, P < 0.01). The survival rate of lymphocytes cultured with TCE (+S9) in TCE-sensitized animals was higher than that in normal animals (83.0% +/- 3.4% vs 63.4% +/- 8.4%, P < 0.05), but no statistically significant difference was found for TCE (-S9) (75.9% +/- 7.9% vs 77.0% +/- 7.2%, P > 0.05).

CONCLUSIONCytotoxicity of TCE to normal lymphocytes and proliferation of sensitized lymphocytes were enhanced by metabolic activation. The metabolites of TCE may act as effective immune hapten to stimulate the proliferation of hapten-specific lymphocytes in TCE-sensitized animals.

Animals ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Cells, Cultured ; Dermatitis, Allergic Contact ; etiology ; immunology ; Female ; Guinea Pigs ; Lymphocytes ; drug effects ; Male ; Passive Cutaneous Anaphylaxis ; drug effects ; Spleen ; drug effects ; immunology ; Trichloroethylene ; toxicity

The residual protein mixture (the content is 4%, approximately), called Salvia miltiorrhiza antigen, was extracted from the Salvia miltiorrhiza cruel materials by mimicking the alcohol-deposit extracts process. Both rabbits and guinea pigs sensitized by Salvia miltiorrhiza could produce specified antibodies. Large molecular antigenic impurities were extracted from the Danshen injection and Xiangdan injection using the centrifugal filtering method. The test results of active systemic anaphylaxis (ASA) and passive cutaneous anaphylaxis (PCA) in guinea pigs confirmed that the extracted antigenic impurities could induce the anaphylaxis reaction in the animals which were sensitized by the Salvia miltiorrhiza antigen. Using the specified antibody produced from rabbits which were sensitiyed by Salvia miltiorrhiza, ELISA test method was developed to test the residual Salvia miltiorrhiza antigenic materials contained in the parenteral Chinese traditional medicines. Calculated as residual protein, the linear range was 0.08-5.12 microg x mL(-1) (r2 = 0.9906), the detection limit and quantization limit are 0.08 microg x mL(-1) and 0.4 microg x mL(-1), respectively. 308 batches of parenteral Chinese traditional medicines containing water-soluable components of Salvia miltiorrhiza were tested, and the Salvia miltiorrhiza antigenic impurities were spotted in 35 (11.4%) batches of samples. The test results show that the extracting process currently used can not remove the Salvia miltiorrhiza antigenic impurities completely, and this may be one of the reasons for anaphylactic reaction in clinics. The proposed ELISA method can be used for improving the manufacture process and for routine quality control of drug products.
Anaphylaxis ; chemically induced ; Animals ; Antigens, Plant ; analysis ; toxicity ; Drug Combinations ; Drugs, Chinese Herbal ; chemistry ; Enzyme-Linked Immunosorbent Assay ; methods ; Female ; Guinea Pigs ; Male ; Passive Cutaneous Anaphylaxis ; drug effects ; Phenanthrolines ; chemistry ; Quality Control ; Rabbits ; Salvia miltiorrhiza ; chemistry

Epigallocatechin gallate (EGCG) is a principle phenolic antioxidant found in a variety of plants, including green and black tea. The anti-allergic effect of EGCG is unknown. The purpose of this study is to investigate the effects of EGCG on compound 48/80-induced mast cell activation and passive cutaneous anaphylaxis. For this, the influences of EGCG on the compound 48/80-induced cutaneous reaction were measured in vivo and the effects of EGCG on the compound 48/80-induced mast cell activations were examined in vitro. Results are below: as 1) EGCG significantly inhibited compound 48/80-induced passive cutaneous anaphylaxis, 2) the compound 48/80-induced degranulation, calcium influx and histamine release of rat peritoneal mast cells (RPMCs) were significantly inhibited by the pretreatment with EGCG, and 3) the compound 48/80-mediated inhibition of cAMP level in RPMCs was significantly increased by the pretreatment with EGCG. These results suggested that EGCG, the most abundant polyphenol in green tea, inhibits the compound 48/80-induced mast cell activation and the increase of vascular permeability, and potentially serve as effective therapeutic tools for allergic diseases.
Animals ; Antioxidants/*pharmacology ; Catechin/*analogs & derivatives/pharmacology ; Cyclic AMP/metabolism ; Histamine Release/*drug effects ; Mast Cells/*drug effects/metabolism ; Passive Cutaneous Anaphylaxis/*drug effects ; Rats ; Research Support, Non-U.S. Gov't ; p-Methoxy-N-methylphenethylamine/*antagonists & inhibitors

AIMTo investigate the effect of cetirizine hydrochloride on the expression of neuropeptide substance P (SP) in IgE-dependent triphasic cutaneous reaction induced by dinitrofluorobenzene (DNFB) in the ears of BALB/c mice.

METHODSBALB/c mice were passively sensitized by intravenous infection of anti-DNP IgE monoclonal antibody 24 h before DNFB challenge. Skin reaction was elicited by applying DNFB to both sides of each ear of sensitized mice. Mice were treated with cetirizine (1 and 10 mg x kg)-1), ig). The ears were removed for pathohistological examination and immunohistochemical staining of SP at different designated times after challenge. The contents of SP in the skin of mouse ear were determined by radioimmunoassay (RIA).

RESULTSThe mice exhibited a triphasic cutaneous reaction with an immediate-phase response (IPR) at 1 h, a late-phase response (LPR) at 24 h and a very late-phase response (vLPR) at 7 days after challenge with DNFB. The expression of SP in different phases increased gradually. Cetirizine (1 and 10 mg x kg(-1)) was shown to significantly inhibit the ear swellings induced by the IPR (P < 0.01), while no obvious effect on the vLPR. The SP contents in ear skin of triphasic cutaneous reaction were decreased by cetirizine.

CONCLUSIONSP is considered to be involved in the pathogenesis of allergic dermatitis. Cetirizine hydrochloride can inhibit the expression of SP in IgE-dependent triphasic cutaneous reaction. It might be part of the mechanisms of anti-anaphylaxis of cetirizine.

Animals ; Anti-Allergic Agents ; pharmacology ; Cetirizine ; pharmacology ; Dose-Response Relationship, Drug ; Ear ; Edema ; metabolism ; Female ; Hypersensitivity, Delayed ; metabolism ; Hypersensitivity, Immediate ; metabolism ; Immunoglobulin E ; immunology ; Mice ; Mice, Inbred BALB C ; Passive Cutaneous Anaphylaxis ; drug effects ; Substance P ; metabolism

OBJECTIVE: There have been many cases of spontaneous adverse drug reactions to fentanyl at a regional pharmacovigilance center in the hospital. To assess the factors causing the adverse drug reactions reported in patients receiving fentanyl patient-controlled analgesia (PCA) monotherapy or in combination with fentanyl transdermal therapeutic system (TTS) for acute post-operative pain management. METHODS: We conducted a retrospective cohort study with all patients prescribed fentanyl PCA for pain management after orthopedic surgery at a single university hospital from June 2012 to May 2013. We analysed the factors causing adverse drug reactions reported by a spontaneous reporting system in patients receiving fentanyl PCA monotherapy and those receiving fentanyl TTS in combination with fentanyl PCA. RESULTS: Based on the spontaneous adverse drug reaction reporting, the risk ratio for the incidence rate of adverse drug reaction in the fentanyl TTS combination therapy group was 3.04 (95 % CI: 2.4-4.00, P < 0.0001), which was approximately 3-fold higher than that reported for fentanyl PCA monotherapy. Only 60 % of the adverse drug reactions were reported. CONCLUSION: It is inappropriate to add fentanyl TTS to fentanyl PCA to manage post-operative acute pain. There is a need to improve adverse drug reaction reporting. We expect that regular analysis of adverse drug reactions reported at regional pharmacovigilance centre would aid in appropriate drug utilization by patients.
Acute Pain ; Analgesia, Patient-Controlled ; Cohort Studies ; Drug Utilization ; Drug-Related Side Effects and Adverse Reactions* ; Fentanyl* ; Humans ; Incidence ; Odds Ratio ; Orthopedics ; Pain Management* ; Passive Cutaneous Anaphylaxis* ; Pharmacovigilance ; Retrospective Studies

OBJECTIVE: To compare the analgesic effects and adverse drug reactions (ADRs) of fentanyl intravenous patient-controlled analgesia (ivPCA) with nefopam, a centrally acting analgesic agent with demonstrated opioid sparing activity, as compared to ketorolac in a tertiary teaching hospital. METHODS: A retrospective evaluation of electronic medical records was conducted on patient records including either nefopam or ketorolac with opioid ivPCA for post-operative pain management in general surgery department from January to December 2014. The status of pain control and ADRs were collected. RESULTS: Out of 6,330 general surgery cases, nefopam was given in 153 prescriptions (6.9%) and ketorolac in 81 prescriptions (3.6%). The level of pain control was not different between two groups (70.9% vs. 75.3%; p = 0.51), but ADRs were more frequently reported in nefopam group (9.8% vs. 2.5%; p < 0.05). New ADRs of hot flushes (n = 1) and paresthesia in hands (n = 1) were reported in nefopam group and they were unlisted in the approved package insert. No serious ADRs were reported in both groups. CONCLUSION: Our findings presented that nefopam showed a similar analgesic effect and higher ADR rates compared to ketorolac as an adjuvant to fentanyl iv PCA for postoperative pain management in general surgery patients in South Korea.
Analgesia, Patient-Controlled ; Analgesics, Opioid ; Drug-Related Side Effects and Adverse Reactions ; Electronic Health Records ; Fentanyl ; Hand ; Hospitals, Teaching ; Humans ; Ketorolac* ; Korea ; Nefopam* ; Pain Management* ; Pain, Postoperative ; Paresthesia ; Passive Cutaneous Anaphylaxis ; Prescriptions ; Product Labeling ; Retrospective Studies

This study is to investigate the anti-allergic effect of anthocyanidin and to explore its possible mechanism. The experiments of passive cutaneous anaphylaxis reaction (PCA) and colorimetry were used to determine the effect of anthocyanidin on degranulation of mast cells in vivo. For in vitro study, various concentrations of anthocyanidin (100, 50 and 25 micromol x L(-1)) were added to the culture medium of mast cells cultured with 100 microg x L(-1) of dinitrophenyl (DNP) specific IgE overnight. The azelastine (100 micromol x L(-1)) was selected as the positive control. The antigen (DNP-human serum albumin, DNP-HAS)-induced release of degranulation was measured by enzymatic assay, histamine was determined by EIA, and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured by Western blotting, separately. In addition, the effects of anthocyanidin on phosphorylation of NF-kappaB, p38MAPK and Akt were observed by Western blotting. The results showed that treatments with anthocyanidin (100 and 50 mg x kg(-1)) were followed by a decrease in PCA of rats. Anthocyanidin (100 and 50 micromol x L(-1)) obviously suppressed the degranulation from mast cells, whereas results from anthocyanidin (100 and 50 micromol x L(-1)) group indicated significant inhibitory effect on histamine, the calcium uptake, TNF-alpha, IL-6, phosphorylation of NF-kappaB, p38MAPK and Akt of mast cells induced by antigen. Anthocyanidin may suppress the anaphylactic reaction by inhibiting the action of mast cells. NF-kappaB, p38MAPK and Akt at least in part contribute to this event.
Animals ; Anthocyanins ; pharmacology ; Anti-Allergic Agents ; pharmacology ; Calcium ; metabolism ; Cell Degranulation ; drug effects ; Histamine Release ; drug effects ; Immunoglobulin E ; immunology ; Interleukin-6 ; metabolism ; Male ; Mast Cells ; immunology ; metabolism ; physiology ; Passive Cutaneous Anaphylaxis ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism