本研究分析了水产养殖和垂钓中饲料、窝料、饵料、水样及水产品中地西泮(Diazepam,DZP)的存在情况,并建立了在线净化-液相色谱串联质谱定量检测方法。结果表明DZP含量在0.5~20.0μg/L间线性良好,相关系数(r^(2))均大于0.999;饵料、水样...本研究分析了水产养殖和垂钓中饲料、窝料、饵料、水样及水产品中地西泮(Diazepam,DZP)的存在情况,并建立了在线净化-液相色谱串联质谱定量检测方法。结果表明DZP含量在0.5~20.0μg/L间线性良好,相关系数(r^(2))均大于0.999;饵料、水样和水产品中定量限(Limit of quantitation,LOQ)分别为1.0μg/kg、0.5μg/L、1.0μg/kg;3种基质中1.0μg/kg、5.0μg/kg和10.0μg/kg 3个浓度水平的加标回收率分别为85.2%~106.5%、82.3%~108.0%、90.7%~116.0%,相对标准偏差(Relative standard deviation,RSD)分别为3.6%~5.1%、2.7%~4.3%、2.1%~2.6%。通过调查发现,7份养殖用饲料中均未检出DZP;28份垂钓中使用的窝料、饵料检出率达66.7%,浓度为2.2~213090.0μg/kg;10份诱鱼剂中均检出DZP,检出率达100%,浓度为637000.0~3471000.0μg/kg;27份水样中DZP检出率达85.2%,浓度为0.4~9.8μg/L和71份淡水鱼中DZP的检出率为54.9%,浓度为0.5~21.8μg/kg。由此可见窝料、饵料及诱鱼剂的使用可能是水体和水产品中DZP频繁检出的重要原因之一,对消费者食用安全和水产养殖行业的健康发展均具有潜在风险,亟需加强DZP监管和监测。展开更多
The present study analyzed expressional changes of excitatory neurotransmitters and inhibitory neurotransmitters in the rat corpus striatum after single-use and combined-use diazepam and Chinese herb moschus. The infl...The present study analyzed expressional changes of excitatory neurotransmitters and inhibitory neurotransmitters in the rat corpus striatum after single-use and combined-use diazepam and Chinese herb moschus. The influence of moschus on the central nervous system was analyzed, in particular whether moschus increased penetration of other drugs into the brain. Reverse-phase high-performance liquid chromatography, which included pre-column derivation with orthophthaladehyde detection, showed varied increased levels of excitatory neurotransmitters, including aspartate and glutamate, and inhibitory neurotransmitters, including glycine and Y-aminobutyric acid, in the corpus striatum after treatment with moschus alone, diazepam alone, or a combination of both. Compared with the diazepam group, aspartate levels significantly decreased at 30 and 60-105 minutes after combined treatment with moschus, while glutamate significantly increased at 45 and 75-105 minutes, glycine levels significantly increased at 105 minutes, and γ-aminobutyric acid increased at 30 and 75-105 minutes. These findings suggested that moschus increased the inhibition effects of diazepam on the brain.展开更多
The protective effect and mechanism of diazepam on ischemia neurons during cerebral ischemia and reperfusion were studied. Sixty three Wistar rats were divided randomly into nine groups: control group , ischemia gro...The protective effect and mechanism of diazepam on ischemia neurons during cerebral ischemia and reperfusion were studied. Sixty three Wistar rats were divided randomly into nine groups: control group , ischemia groups including subgroups of is3h, is3 h/rep1 h, is3 h/rep2 h, is3 h/rep3 h, diazepam treated groups , including subgroups of is3 h, is3 h/rep1 h, is3 h/rep2 h, is3 h/rep3 h with Zea longa's animal model of middle cerebral artery occlusion. The comparison between the ischemia group and diazepam treated group showed that diazepam could obviously decrease the production of glutamate, asparate, MDA and increase the synthesis and release of GABA, SOD and GSH PX. It was concluded that diazepam exerted its protective effects on neurons through complex mechanisms of regulating the synthesis and release of excitotary/inhibitory amino acids and free radicals.展开更多
OBJECTIVE Investigate the effects of diazepam(DZP) on γ2 subunit containing GABA type A receptor(GABA A R) trafficking.METHODS Immunofluorescence microscopy measured surface GABA A Rs and gephyrin in rat cortical neu...OBJECTIVE Investigate the effects of diazepam(DZP) on γ2 subunit containing GABA type A receptor(GABA A R) trafficking.METHODS Immunofluorescence microscopy measured surface GABA A Rs and gephyrin in rat cortical neurons after 24 h exposure of 1.0 μmol·L^(-1) DZP.Biochemical studies of mice injected with 10 mg·kg^(-1) DZP vs vehicle were assessed for γ2 subunit and total gephyrin cortical levels 12 h post-injection.Ubiquitination of the γ2 subunit was studied by immunoprecipitation after 12 h of 1.0 μmol·L^(-1) DZP exposure.A γ2 subunit encoding an N terminal fluorogen-activating peptide and pH-sensitive green fluorescent protein(γ2 pH FAP) measured lysosomal targeting of γ2 containing GABA A Rs.RFP-gephyrin and γ2 pH FAP synaptic diffusion rates were examined using fluorescence recovery after photobleaching(FRAP).RESULTS Extrasynaptic levels of γ2 GABA A Rs decreased by 12.2%,while synaptic gephyrin S270 phosphorylation increased by 18.3% in DZP-treated neurons after 24 h compared to control(P<0.05).Dendritic levels of gephyrin were also reduced to 74.1% of control,while S270 phosphorylation was elevated by 25.2%(P<0.05;P<0.01).Mice 12 h post-DZP injection demonstrated a 12.7% and 26.1% decrease in total γ2 and gephyrin levels,respectively(P<0.05;P<0.01).12 h DZP treatment enhanced γ2 subunit ubiquitination 1.13-fold relative to control(P<0.05).Internalized γ2 pH FAP GABA A Rs associated with lysosomes was 8.0% higher in neurons treated with 12-16 h DZP compared to control.Pilot FRAP experiments suggest gephyrin and γ2 have increased mobility and turnover at synapses following DZP.CONCLUSION DZP treatment decreases γ2 GABA A R levels and gephyrin scaffolding function after one day of exposure,which may contribute to the formation of DZP tolerance.展开更多
AIM:To investigate risk factors and adverse events related to high-dose diazepam administration during endoscopic submucosal dissection for gastric neoplasias.METHODS:Between February 2002 and December 2009,a total of...AIM:To investigate risk factors and adverse events related to high-dose diazepam administration during endoscopic submucosal dissection for gastric neoplasias.METHODS:Between February 2002 and December 2009,a total of 286 patients with gastric epithelial neoplasia underwent endoscopic submucosal dissection in our hospital.To achieve moderate sedation,5-7.5 mg of diazepam was administered intravenously by non-anesthesiologists.Intermittent additional administration of 2.5-5 mg diazepam was performed if uncontrollable body movement of the patient was observed.All patients were classified into groups based on the required diazepam dose:low-dose (≤ 17.5 mg,n=252) and high-dose (> 17.5 mg,n=79).RESULTS:Differences between the low-and highdose diazepam groups were observed in lifetime alcohol consumption (0.30 ± 0.48 vs 0.44 ± 0.52 tons,P=0.032),body weight (58.4 ± 10.3 vs 62.0 ± 9.9 kg,P=0.006),tumor size (15 ± 10 vs 23 ± 18 mm,P < 0.001),lesion location (P < 0.001) and the presence of ulcerative findings (14/238 vs 18/61,P < 0.001).Multivariate analysis identified all five variables as independently related to required diazepam dosage.In terms of adverse reactions to diazepam administration,paradoxical excitement was significantly more frequent in the high-dose diazepam group (P < 0.001).CONCLUSION:Intermittent administration of diazepam enabled safe completion of gastric endoscopic submucosal dissection except in patients who were alcohol abusers or obese,or who showed complicated lesions.展开更多
文摘本研究分析了水产养殖和垂钓中饲料、窝料、饵料、水样及水产品中地西泮(Diazepam,DZP)的存在情况,并建立了在线净化-液相色谱串联质谱定量检测方法。结果表明DZP含量在0.5~20.0μg/L间线性良好,相关系数(r^(2))均大于0.999;饵料、水样和水产品中定量限(Limit of quantitation,LOQ)分别为1.0μg/kg、0.5μg/L、1.0μg/kg;3种基质中1.0μg/kg、5.0μg/kg和10.0μg/kg 3个浓度水平的加标回收率分别为85.2%~106.5%、82.3%~108.0%、90.7%~116.0%,相对标准偏差(Relative standard deviation,RSD)分别为3.6%~5.1%、2.7%~4.3%、2.1%~2.6%。通过调查发现,7份养殖用饲料中均未检出DZP;28份垂钓中使用的窝料、饵料检出率达66.7%,浓度为2.2~213090.0μg/kg;10份诱鱼剂中均检出DZP,检出率达100%,浓度为637000.0~3471000.0μg/kg;27份水样中DZP检出率达85.2%,浓度为0.4~9.8μg/L和71份淡水鱼中DZP的检出率为54.9%,浓度为0.5~21.8μg/kg。由此可见窝料、饵料及诱鱼剂的使用可能是水体和水产品中DZP频繁检出的重要原因之一,对消费者食用安全和水产养殖行业的健康发展均具有潜在风险,亟需加强DZP监管和监测。
文摘The present study analyzed expressional changes of excitatory neurotransmitters and inhibitory neurotransmitters in the rat corpus striatum after single-use and combined-use diazepam and Chinese herb moschus. The influence of moschus on the central nervous system was analyzed, in particular whether moschus increased penetration of other drugs into the brain. Reverse-phase high-performance liquid chromatography, which included pre-column derivation with orthophthaladehyde detection, showed varied increased levels of excitatory neurotransmitters, including aspartate and glutamate, and inhibitory neurotransmitters, including glycine and Y-aminobutyric acid, in the corpus striatum after treatment with moschus alone, diazepam alone, or a combination of both. Compared with the diazepam group, aspartate levels significantly decreased at 30 and 60-105 minutes after combined treatment with moschus, while glutamate significantly increased at 45 and 75-105 minutes, glycine levels significantly increased at 105 minutes, and γ-aminobutyric acid increased at 30 and 75-105 minutes. These findings suggested that moschus increased the inhibition effects of diazepam on the brain.
基金This project was supported by a grant from a nationalnatural sciences foundation of China (No. 30 0 40 0 37)
文摘The protective effect and mechanism of diazepam on ischemia neurons during cerebral ischemia and reperfusion were studied. Sixty three Wistar rats were divided randomly into nine groups: control group , ischemia groups including subgroups of is3h, is3 h/rep1 h, is3 h/rep2 h, is3 h/rep3 h, diazepam treated groups , including subgroups of is3 h, is3 h/rep1 h, is3 h/rep2 h, is3 h/rep3 h with Zea longa's animal model of middle cerebral artery occlusion. The comparison between the ischemia group and diazepam treated group showed that diazepam could obviously decrease the production of glutamate, asparate, MDA and increase the synthesis and release of GABA, SOD and GSH PX. It was concluded that diazepam exerted its protective effects on neurons through complex mechanisms of regulating the synthesis and release of excitotary/inhibitory amino acids and free radicals.
基金supported by National Institute of Health(T32GM008424)Whitehall Foundation+1 种基金William C DEGROAT Neuropharmacology Departmental FellowshipPharmacology and Chemical Biology Startup Funds
文摘OBJECTIVE Investigate the effects of diazepam(DZP) on γ2 subunit containing GABA type A receptor(GABA A R) trafficking.METHODS Immunofluorescence microscopy measured surface GABA A Rs and gephyrin in rat cortical neurons after 24 h exposure of 1.0 μmol·L^(-1) DZP.Biochemical studies of mice injected with 10 mg·kg^(-1) DZP vs vehicle were assessed for γ2 subunit and total gephyrin cortical levels 12 h post-injection.Ubiquitination of the γ2 subunit was studied by immunoprecipitation after 12 h of 1.0 μmol·L^(-1) DZP exposure.A γ2 subunit encoding an N terminal fluorogen-activating peptide and pH-sensitive green fluorescent protein(γ2 pH FAP) measured lysosomal targeting of γ2 containing GABA A Rs.RFP-gephyrin and γ2 pH FAP synaptic diffusion rates were examined using fluorescence recovery after photobleaching(FRAP).RESULTS Extrasynaptic levels of γ2 GABA A Rs decreased by 12.2%,while synaptic gephyrin S270 phosphorylation increased by 18.3% in DZP-treated neurons after 24 h compared to control(P<0.05).Dendritic levels of gephyrin were also reduced to 74.1% of control,while S270 phosphorylation was elevated by 25.2%(P<0.05;P<0.01).Mice 12 h post-DZP injection demonstrated a 12.7% and 26.1% decrease in total γ2 and gephyrin levels,respectively(P<0.05;P<0.01).12 h DZP treatment enhanced γ2 subunit ubiquitination 1.13-fold relative to control(P<0.05).Internalized γ2 pH FAP GABA A Rs associated with lysosomes was 8.0% higher in neurons treated with 12-16 h DZP compared to control.Pilot FRAP experiments suggest gephyrin and γ2 have increased mobility and turnover at synapses following DZP.CONCLUSION DZP treatment decreases γ2 GABA A R levels and gephyrin scaffolding function after one day of exposure,which may contribute to the formation of DZP tolerance.
基金Supported by A Grant-in-Aid for Cancer Research from the Ministry of Health,Labor and Welfare of Japan,in part
文摘AIM:To investigate risk factors and adverse events related to high-dose diazepam administration during endoscopic submucosal dissection for gastric neoplasias.METHODS:Between February 2002 and December 2009,a total of 286 patients with gastric epithelial neoplasia underwent endoscopic submucosal dissection in our hospital.To achieve moderate sedation,5-7.5 mg of diazepam was administered intravenously by non-anesthesiologists.Intermittent additional administration of 2.5-5 mg diazepam was performed if uncontrollable body movement of the patient was observed.All patients were classified into groups based on the required diazepam dose:low-dose (≤ 17.5 mg,n=252) and high-dose (> 17.5 mg,n=79).RESULTS:Differences between the low-and highdose diazepam groups were observed in lifetime alcohol consumption (0.30 ± 0.48 vs 0.44 ± 0.52 tons,P=0.032),body weight (58.4 ± 10.3 vs 62.0 ± 9.9 kg,P=0.006),tumor size (15 ± 10 vs 23 ± 18 mm,P < 0.001),lesion location (P < 0.001) and the presence of ulcerative findings (14/238 vs 18/61,P < 0.001).Multivariate analysis identified all five variables as independently related to required diazepam dosage.In terms of adverse reactions to diazepam administration,paradoxical excitement was significantly more frequent in the high-dose diazepam group (P < 0.001).CONCLUSION:Intermittent administration of diazepam enabled safe completion of gastric endoscopic submucosal dissection except in patients who were alcohol abusers or obese,or who showed complicated lesions.
