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1.
《Clinical gastroenterology and hepatology》2022,20(8):1776-1783.e4
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Schizophrenia is a chronic and severe psychiatric disorder that has profound impact on an individual’s life and on society. Thus, developing more effective therapeutic interventions is essential. Over the past quarter‐century, an abundance of evidence from pharmacologic challenges, post‐mortem studies, brain imaging, and genetic studies supports the role of glutamatergic dysregulation in the pathophysiology of schizophrenia, and the results of recent randomized clinical trials based on this evidence have yielded promising results. In this article, we review the evidence that alterations in glutamatergic neurotransmission, especially focusing on the N‐methyl‐d ‐aspartate receptor (NMDAR) function, may be a critical causative feature of schizophrenia, how this contributes to pathologic circuit function in the brain, and how these insights are revealing whole new avenues for treatment development that could reduce treatment‐resistant symptoms, which account for persistent disability. 相似文献
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Metabolic abnormalities of gastrointestinal mucosa in celiac disease: An in vitro proton nuclear magnetic resonance spectroscopy study
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小鼠持续性脑缺血后NMDA受体亚单位表达的变化 总被引:7,自引:1,他引:6
目的:研究小鼠持续性脑缺血后不同脑区NMDA受体亚单位表达的变化及其与病理损伤之间的联系。方法:采用大脑中动脉阻断法制作小鼠持续性脑缺血模型,取缺血后不同时间的皮层、海马、皮层下脑组织,用免疫印迹技术测定NMDA受体亚单位ζ1和ε1及ε2蛋白的含量。同时作冰冻切片和苏木素伊红染色,计算相应脑区神经元密度。结果:NMDA受体ζ1和ε1及ε2亚单位表达的改变发生于缺血后5h内,皮层下3个亚单位表达均明显增加,海马则各亚单位表达变化不一。脑梗塞灶和相关脑区神经元密度显著减小均出现于缺血后5h,相关脑区神经元死亡严重程度依次为皮层下组织和海马CA1区及大脑颞叶皮层Ⅲ-Ⅳ层。结论:小鼠持续性脑缺血,缺血侧脑组织NMDA受体亚单位ζ1和ε1及ε2表达的变化发生在明显的病理损害之前,表达变化程度因脑区不同,与相关脑区神经元损害的程度相应。 相似文献
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Spermidine/Spermine N-Acetyltransferase, a New Biochemical Marker for Epithelial Proliferation in Rat Bladder 总被引:4,自引:4,他引:0
Isao Matsui-Yuasa Shuzo Otani Yoshihisa Yano Nobuyasu Takada Masa-Aki Shibata Shoji Fukushima 《Cancer science》1992,83(10):1037-1040
We examined the activity of spermidine/spermine N 1 -acetyltransferase (SAT), a rate-limiting enzyme of the biodegradation of polyamines, in N -butyl- N -(4–hydroxybutyI)nitrosamine-induced transitional cell carcinoma (TCC) and melamine-induced papillomatosis of rat bladder, and compared the activity to that of ornithine decarboxylase (ODC). Both activities were higher in both lesions than in control rats. The difference between SAT and ODC activities in cancerous tissue and papillomatosis was not significant. Cells stained for proliferating cell nuclear antigen (PCNA) were abundant in papillomatosis. TCC had areas with much PCNA. The results indicated that an elevation of SAT activity occurs in both reversible and irreversible proliferation of bladder epithelium and could be important in bladder carcinogenesis. 相似文献
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新生大鼠反复惊厥对NMDA受体表达的长期影响 总被引:6,自引:0,他引:6
目的:研究反复惊厥对大鼠脑内N-甲基-D-天门冬氨酸(NMDA)受体表达,以及成年期认知功能和惊厥阈的长期影响。方法:生后6d(用P6表示,下同)的Wistar大鼠随机分成两组,每组6只,惊厥组每日吸入三氟乙醚诱导惊厥发作1次,每次持续30min,连续6d;对照组同样操作但不吸入三氟乙醚。两组大鼠于P60-P65行Morris水迷宫实验,检测大鼠的学习记忆功能。于P75时给予大鼠腹腔注射戊四唑(PTZ)测定大鼠的惊厥阈。随即断头处死大鼠,分离大脑皮质和海马,匀浆提取细胞膜蛋白,应用免疫印记法测定NMDA受体亚基l(NRl)和NR2A-2D表达的变化。结果:从P6l至P65,两组大鼠寻找平台时间均逐渐缩短,惊厥组大鼠在P65的平均寻找平台时间较对照组显著延长。惊厥组大鼠注射PTZ后发生惊厥的潜伏期与对照组比较差异无显著性。在大脑皮层,惊厥组大鼠较对照组NRl和NR2B表达水平明显下调,在海马这两种亚基表达水平无明显改变,在大脑皮层和海马区,惊厥组较对照组NR2A表达水平明显下调,NR2C表达水平明显上调。两组在皮层和海马均无NR2D表达。结论;新生大鼠反复惊厥可导致远期认知障碍,同时伴有NMDA受体的数量和结构上的长期改变,NMDA受体表达的这种改变可能在发育期惊厥导致的脑长期认知功能损害中起重要作用。 相似文献
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The antitumorigenic effect of cryptoporic acid E (CPA-E), a dimeric drimane sesquiterpenoid isolated from the fungus Cryptoporus volvatus , on colon carcinogenesis was investigated. Female F344 rats given an intrarectal instillation of 2 mg of N-methyl-N-nitrosourea 3 times weekly in weeks 1 and 2 were fed diet containing 0.2% CPA-E from week 3. Femal ICR mice given 15 weekly intraperitoneal injections of 10 mg of 1,2-dimethylhydrazine/kg body weight during weeks 1 to 15 were fed diet containing 0.06% CPA-E from week 1. The experiment was terminated at week 35 for rats and at week 25 for mice. The incidence and the number of tumors per animal were reduced in CPA-E-fed animals compared to the controls: 31% vs. 75% (P<0.05) and 0.4±0.2 (SEM) vs. 0.9 ± 0.2 (0.1> P >0.05) in rats, and 31% vs. 63% (0.1>P>0.05) and 0.4±0.2 vs. 2.4 ± 0.8 (P<0.05) in mice (16 animals in each group). Intrarectal deoxycholic acid-induced colonic mucosal ornithine decarboxylase activity was significantly lowered in CPA-E-fed animals compared to controls. This shows an antipromoting activity of CPA-E against colon carcinogenesis. Thus, it was concluded that CPA-E inhibits colon cancer development in both rats and mice treated with 2 different colon carcinogens. 相似文献
10.
Relaxation times of choline, creatine and N-acetyl aspartate in human cerebral white matter at 1.5 T
Several studies have investigated the T1 and T2 relaxation time of choline, creatine and N-acetyl aspartate in cerebral white matter in normal human subjects. However, these studies demonstrate a large variation in T1 and T2 values. In the present study, relaxation times of choline, creatine and N-acetyl aspartate were determined in cerebral white matter in 15 control subjects (age 21 +/- 2 y, mean +/- SD) at 1.5 T. Using PRESS, seven or eight data points were obtained to fit the T1 and T2 relaxation curves to, respectively. The mean voxel size was 14 cm3. The T1 relaxation times of choline, creatine and N-acetyl aspartate were 1091 +/- 132 (mean +/- SD), 1363 +/- 137 and 1276 +/- 132 ms. The T2 relaxation times were 352 +/- 52, 219 +/- 29 and 336 +/- 46 ms, respectively. 相似文献