1.Genetic predictors of antipsychotic-induced weight gain: a case-matched multi-gene study
Renrong WU ; Jingping ZHAO ; Ping SHAO ; Jianjun OU ; Maihui CHANG
Journal of Central South University(Medical Sciences) 2011;36(8):720-723
Objective To determine associations between weight gain induced by antipsychotic and the polymorphisms of HTR2C gene -759C/T and -697G/C,histamine-1 receptor gene,leptine gene -2548G/A,and adiponectin gene +276G/T and +45T/G.Methods In the casematched study,85 patients who gained more than 7% of their pre-drug body weight served as the study group and another 85 patients who gained less than 7% of their pre-drug body weight served as the control group.The ligation diction reaction technique was used to analyze the frequencies of the -759C/T and -697G/C polymorphism of the HTR2C gene,-2548A/G polymorphism of leptin gene,+ 276G/T and + 45T/G polymorphism of adiponectin gene and glu349asp polymorphism of H1 receptor gene.Results The presence of the -759C allele,-697G allele,-2548A allele and + 276G allele was significantly higher in the study group than that in the control group (P < 0.05 ).Conclusion The -759C/T and -697G/C polymorphisms of the promoter region of 5HT2C receptor gene,-2548A/G polymorphisms of leptin gene and + 276G/T polymorphisms of adiponectin gene may be associated with the antipsychotic induced weight gain.The glu349asp polymorphisms of histamine-1 receptor gene is not associated with antipsychotic induced weight gain.
2.Cellular uptake characteristics of salvianolic acid B in myocardial cells and blood vessel endothelial cells
Jingping SHAO ; Shanfei ZHANG ; Yuancheng CHEN ; Wenliang YANG ; Xiaoquan LIU
Journal of China Pharmaceutical University 2009;40(3):263-268
Aim: To determine the uptake characteristics of salvianolic acid B(Sal B) in myocardial cells and blood vessel endothelial cells. Method: The effects of various factors, such as time, temperature, drug concentration, pH of the medium, on the uptake of Sal B in myocardial cells and aorta endothelial cells were investigated. LC/MS was employed to determine the intracellular concentration of Sal B. Results: Uptake kinetics of Sal B in the myocardial cells and aorta endothelial cells fitted well to the logarithmic model at 37 ℃ and 4 ℃. The a-mount of uptake was in direct proportion to the extracellular concentration of Sal B in the experimental concentration range. Uptake of Sal B both in the myocardial cells and blood vessel endothelial cells would significantly increase while the medium pH decreased, and some water-soluble components extracted from danshen would also facilitate the uptake of Sal B both in the myocardial cells and blood vessel endothelial cells obviously. The energy metabolism inhibitors would significantly inhibit the uptake of Sal B in the myocardial cells and blood vessel endothelial cells. When lactic acid and fatty acid were added to the incubation solution, the uptake of Sal B both in the myocardial cells and aorta endothelial cells increased more than 20%. Conclusion: pH is the most important factor influencing the cellular uptake of Sal B, and the amount of uptake tends to increase in acidic medium. Results suggest that the uptake of Sal B would increase in the acidified internal environment induced by myocardial ischemia, thus exerting better cardiovascular activities.
3.Effects of ziprasidone and olanzapine on glucose and lipid metabolism in first-episode schizophrenia.
Ping SHAO ; Jianjun OU ; Renrong WU ; Maosheng FANG ; Honghui CHEN ; Yi XU ; Jingping ZHAO
Journal of Central South University(Medical Sciences) 2013;38(4):365-369
OBJECTIVE:
To investigate the effect of ziprasidone and olanzapine on glucose and lipid metabolism in first-episode schizophrenia.
METHODS:
A total of 260 schizophrenics were assigned randomly to receive ziprasidone or olanzapine for 6 weeks. The weight was measured at baseline, week 2, 4 and 6. Fasting blood glucose (FBS), fasting insulin, high-density lipoprotein (HDL), total-cholesterol (TC) and triglycerides (TG) were measured at baseline and the end of 6-week treatment. Low-density lipoprotein (LDL) was measured in some patients at baseline and the end of 6-week treatment. Body mass index (BMI) and insulin resistance index (IRI) were counted.
RESULTS:
A total of 245 patients completed the trial, including 121 ziprasidone patients and 124 olanzapine patients. The average dose was 137.5 mg/d for ziprasidone and 19.5 mg/d for olanzapine. Patients treated with olanzapine had higher weight gain than those treated with ziprasidone [(4.55±3.37) kg vs (-0.83±2.05) kg, P<0.001]. After the treatment, FBS, fasting insulin, HDL, TC, TG, LDL and IRI levels were significantly increased in the olanzapine group (all P values<0.001 ). However, in the ziprasidone group, FBS decreased significantly and HDL and TG levels increased significantly after the 6-week treatment (all P values<0.05). The mean changes of FBS, fasting insulin, TC, TG, LDL and IRI were significantly different in the two groups (all P values<0.001).
CONCLUSION
Ziprasidone has less glucose and lipid metabolic effect for first-episode schizophrenia patients in short-term treatment. However, olanzapine induces weight gain and dysfunction of glucose and lipid metabolism significantly, which is associated with increased risk of complications. When the doctors choose antipsychotics in the clinic, they should consider the side effects of the medication.
Adolescent
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Adult
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Benzodiazepines
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adverse effects
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therapeutic use
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Blood Glucose
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drug effects
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Female
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Humans
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Lipid Metabolism
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drug effects
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Male
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Middle Aged
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Olanzapine
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Piperazines
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adverse effects
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therapeutic use
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Schizophrenia
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drug therapy
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Thiazoles
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adverse effects
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therapeutic use
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Young Adult