1.Signal mining and analysis of adverse drug events of abatacept based on FAERS database
Maowei GAO ; Xiaojuan YANG ; Shangshang ZONG
China Pharmacy 2023;34(15):1884-1890
OBJECTIVE To provide a reference for the safe use of abatacept in clinic. METHODS Based on the United States FDA Adverse Event Reporting System (FAERS) database, the generic name of the drug “abatacept” and the trade name “Orencia” were used as the search keywords to retrieve drug adverse event (ADE) signal of abatacept as primary suspected drug. The reported odds ratio method and proportional reporting ratio method in the proportional imbalance method and Excel 2020 software were used to mine and analyze the signals. RESULTS A total of 93 189 abatacept-induced ADE reports were retrieved, mainly female cases (75.98%), and the age was mainly concentrated in 18-64 years old (35.17%); main countries reporting data were the United States (47.41%) and Canada (30.59%), and the number of reports was generally increasing year by year. A total of 3 092 ADE signals were screened, of which the signals associated with the primary disease were similar to those described in the drug instruction of abatacept, such as rheumatoid arthritis, arthralgia, joint swelling, etc.; followed by ADE signals related to infusion reactions, including pain, fatigue, rash, etc. All selected ADE signals involved 27 system organ classes, mainly involved systemic diseases and drug site conditions, musculoskeletal and connective tissue diseases, injury, poisoning and surgical complications, infections and invasive diseases, gastrointestinal diseases, neurological diseases, respiratory, thoracic and mediastinal diseases, heart diseases, benign, malignant and unspecified tumors and reproductive system and breast diseases, etc. A total of 22 ADE signals were not included in the drug instructions of abatacept among the top 50 ADE signals in the number list of reported cases, including fatigue, drug intolerance, abdominal discomfort, swelling, lupus erythematosus, peripheral swelling, cell sores, diarrhea, elevated liver enzymes and lower respiratory tract infection, etc. CONCLUSIONS In the process of clinical use of abatacept, special attention should be paid to infection and its carcinogenicity, while assessing the risk of respiratory and cardiovascular system diseases in patients; when patients suffer from these two underlying diseases, the pros and cons should be weighed carefully before selecting drug; in addition, the drug-induced ADE in the neurological, gastrointestinal and reproductive system cannot be ignored.
2.Effect of glucocorticoid on differentiation of bone marrow mesenchymal cells
Le LIN ; Yuzhong GAO ; Maowei YANG ; Guangyu FAN
Chinese Journal of Tissue Engineering Research 2009;13(45):8935-8938
BACKGROUND:Lipopexia induced by glucocorticoid is fat precipitation in marrow due to abnormal lipomatabolism,or differentiation of cells resulting from hormone-affected bone marrow mesenchymal cells.The precise generating procedure remains unclear.OBJECTIVE:To Jnvastigate effects of vadous concentrations of dexamethasone on adipogenic differentiation of bone marrow mesenchymal cells.DESIGN,TIME AND SETTING:The observational study was performed at the Department of Biochemistry,China Medical University from January 2007 to January 2009.MATERIALS:A total of 80 Sprague-Dawley rats aged 3 or 4 weeks,weighing (110±10) g,of both genders,were used in this study.METHODS:Rat bone marrow mesenchymal cells were isolated and subcultured.Bone marrow masenchymal cells at the third passage were used as samples.MAIN OUTCOME MEASURES:Cellular morphologic changes after treatment of 10~(-7) mol/L dexamethasone were observed under an inverted microscope,as well as at 3,7,14 and 21 days under normal culture condition.Morphological changes of bone marrow mesenchymal cells were observed following alkaline phosphatase and Sudan Ⅲ staining.Alkaline phosphatase activity was measured using phenol reagent.Effects of dexamethasone on cell proliferation were measured using MTT assay.RESULTS:Following 24 hours of incubation,a few adherent cells were found in the bottom of the culture flask,showing spindle shape.With prolonged time,adherent cells became more,presenting radiated shape.Following passage,cells distributed uniformly,showing typical fibroblast-shape.Following dexamethasone stimulation,cells changed from spindle-shape into polygonal or irregular shape.In the late phase,with increased concentration and prolonged time,cell colonies disappeared;cells adhered,and died.In normal cultured cells,no or a few orange particles were found.In dexamethasone-cultured cells,with increased hormone concentration and prolonged time,Sundan Ⅲ stained particles increased.At 21 days,alkaline phosphatase activity under normal culture was separately 1.57-,4.49-and 5.0-fold of 10~(-8),10~(-7),10~(-6) mol/L dexamethasone group.At 7,14 and 21 days,alkaline phosphatase activity under normal culture was separately 2.93-,3.80-and 4.39-fold of 10~(-7) mol/L dexamethasone group (P < 0.05).High concentration of dexamethasone had significant inhibitory effects on cell proliferation activity.Significant difference was detected as compared 10~(-7) mol/L and 10~(-6) mol/L to other groups (P < 0.05).CONCLUSION:High-dose dexamethasone enhances adipogenic and suppresses osteoblastic differentiation of bone marrow mesenchymal cells.The effect will increase along with the increasing content and prolonged duration of demamethasone stimulation.

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