OBJECTIVETo develop animal models and methodologies for assay of pseudoallergy induced by injectable drugs.

METHODRats cutaneous anaphylactoid reaction model was developed by intravenous injection of 0. 6% Evans blue(EB) followed by intracutaneous injection of test substance solutions 50 microL. Diameters of subcutaneous blue spots and EB exudation were assayed.

RESULTRat anaphylactoid reaction was characterized as vascular hyperpermeability which was measured by diameters of blue spots inside the skin and the EB exudation of the blue spots. Compound 48/80 caused severe bluing and EB exudation in the skin by inducing obvious vascular hyperpermeability which indicated that it can induce rat skin pseudoallergy. Normal saline or 5% glucose injection showed no obvious reactions. The rat pseudoallergy model was validated by intracutaneous injections of western drug injections and Chinese medicine.

CONCLUSIONRats could be developed into skin pseudoallergy model for preclinical safety evaluation of injectable drugs. The pseudoallergy reaction in this model is of high clinic consistency, sensitivity, reproducibility, and maneuverability. The model is suitable for the evaluation for pseudoallergy induced by injectable products prepared from Chinese materia medica This model can also be used for safety assay and quality control in manufacturing process, spot checking of marketed products, screening of allergen as well as studying of pseudoallergy mechanism.

Animals ; Disease Models, Animal ; Drug Evaluation, Preclinical ; methods ; Drug Hypersensitivity ; Female ; Injections, Subcutaneous ; methods ; Male ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects

OBJECTIVETo develop animal models and methodologies for assay of pseudoallergy induced by injectable drugs.

METHODMouse anaphylactoid reaction model was developed by intravenous injection of test substance solutions containing Evans blue (EB). Scores of ear blue staining and quantitation of ear EB exudation were the parameters for the pseudoallergy reaction.

RESULTMouse anaphylactoid reaction was characterized as vascular hyperpermeability which was detectable in ears by quantitation of blue staining score and EB exudation. Compound 48/80 and histamine caused severe ear bluing and EB exudation by inducing obvious vascular hyperpermeability which indicated that they can induce mouse pseudoallergy. Intravenous injection of either normal saline or 5% glucose injection showed no ear bluing. The mouse pseudoallergy model was validated by intravenous injections of western drugs and Chinese medicine.

CONCLUSIONMice could be developed into pseudoallergy model for preclinical safety evaluation of injectable drugs. The pseudoallergy reaction in this model is of high clinic consistency, sensitivity, reproducibility, and maneuverability. The model is suitable for the evaluation for pseudoallergy induced by injectable products prepared from Chinese materia medica This model can also be used for safety assay and quality control in manufacturing process, spot checking of marketed products, screening of allergen as well as studying of pseudoallergy mechanism.

Animals ; Disease Models, Animal ; Drug Evaluation, Preclinical ; methods ; Drug Hypersensitivity ; Injections, Intravenous ; Mice ; Mice, Inbred ICR

Objective:To evaluate the teaching effectiveness of independent experimental design from students' active learning behavior, and further provide the basis for advancing the reform of functional experimental teaching and teaching quality.Methods:In June 2019, 186 undergraduates (5-year-programme and 8-year-programme) of Xiangya School of Medicine were included in the teaching research. Self-administered questionnaires were applied to characterize students' active learning behavior in independent experimental design education. Spearman rank correlation analysis and Logistic regression analysis were used in the study. SPSS 23.0 was used for descriptive analysis of the data.Results:During the independent experimental design, 85.0%(158/186) of the students thought it was necessary and important to conduct independent experimental design education; 72.6%(135/186) of the students tentatively raised new scientific questions; 97.8%(182/186) of the students actively searched literature; 77.4%(144/186) of the students participated in reply positively. The value of correlation coefficient of actively learning behavior "tentatively raising new science questions" and teaching effectiveness "improving the ability of scientific thinking" was 0.81. And only 42.5%(79/186) of the students agreed that students needed to summarize after reporting.Conclusion:Independent experimental design education is welcomed and widely accepted by students, which has effectively improved the capacity for scientific research and innovation spirit of students. Whether students' active learning behavior can be fully mobilized in the education practice is closely related to the teaching effect. And the cultivation of leadership and leading consciousness still need to be improved.

Objective:To analyze the clinical characteristics, therapeutic options and risk factors of mortality in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infection, and to provide evidence for clinical treatment option and prognosis evaluation of CRAB bloodstream infections. Methods:A retrospective study was carried out in 224 patients with confirmed diagnosis of CRAB bloodstream infection during the period from January 2012 to December 2017 in West China Hospital, Sichuan University. The patients were divided into the death group and the survival group according to the survival status 28 days after collecting blood samples. The clinical features and therapeutic options of antibacterial drugs were reviewed. Student′s t test was used for analyzing normally distributed data and Mann-Whitney U test for non-normal data.Chi-square test was used for categorical variables. Univariate and multivariate logistic analysis were used to analyze the risk factors of mortality associated with CRAB bloodstream infection. Results:Among 224 cases of CRAB bloodstream infection, 121 cases died (54.02%). These patients were mainly in intensive care unit (ICU) and hematology department. The common underlying diseases were severe acute pancreatitis and severe cardiovascular events. The interleukin (IL)-6 level (median (interquartile range)) in the death group (480.40 ng/L (1 432.95 ng/L)) was higher than that of the survival group (107.05 ng/L (263.08 ng/L)), the difference was statistically significant ( Z=4.526, P<0.01). The procalcitionin (PCT) levels in the death group and the survival group were 3.81 μg/L (17.26 μg/L) and 2.12 μg/L (12.74 μg/L), respectively, with no difference between the two groups ( P>0.05). The death rate of empirical treatment with a single or more non-active antimicrobial agents was 57.14% (64/112), that of monotherapy with active agent was 45.68% (37/81), and that of combination therapy with at least one active drug was 64.52% (20/31). The differences had no statistical significance ( P=0.130). The logistic regression analysis showed that the risk factors of mortality associated with CRAB bloodstream infection were renal dysfunction (odds ratio ( OR)=2.181, P=0.024) and multiple organ dysfunction syndrome (MODS; OR=20.376, P<0.01). Conclusions:The fatality rate of patients with CRAB bloodstream infection is high. These patients with renal dysfunction or MODS have poor prognosis. In addition to early effective antibacterial therapy, individual comprehensive treatment should be implemented in order to improve the curative effect.

The loss of endothelial connective integrity and endothelial barrier dysfunction can lead to increased vascular injury, which is related to the activation of endothelial inflammasomes. There are evidences that low concentrations of aspirin can effectively prevent cardiovascular diseases. We hypothesized that low-dose aspirin could ameliorate endothelial injury by inhibiting the activation of NLRP3 inflammasomes and ultimately prevent cardiovascular diseases. Microvascular endothelial cells were stimulated by lipopolysaccharide (2 μg/mL) and administrated by 0.1-2 mmol/L aspirin. The wild type mice were stimulated with LPS (100 μg/kg/day), and 1 h later treated with aspirin (12.5, 62.5, or 125 mg/kg/day) and dexamethasone (0.0182 mg/kg/day) for 7 days. Plasma and heart were harvested for measurement of ELISA and immunofluorescence analyses. We found that aspirin could inhibit NLRP3 inflammasome formation and activation in dose-dependent manner and has correlation between the NLRP3 inflammasome and the ROS/TXNIP pathway. We also found that low-concentration aspirin could inhibit the formation and activation of NLRP3 inflammasome and restore the expression of the endothelial tight junction protein zonula occludens-1/2 (ZO1/2). We assume that aspirin can ameliorate the endothelial layer dysfunction by suppressing the activation of NLRP3 inflammasome.