大鼠体外循环模型的建立与应用

由于操作简便、节省人力物力，大鼠体外循环模型的应用愈加广泛。大鼠在小型呼吸机辅助下，应用颈静脉插管入右心房引流血液至贮血瓶，在蠕动移液泵作用下，经膜式氧合器氧合、变温器变温，通过股动脉或尾动脉插管注入动脉系统，建立体外循环回路。有血预充、减少总预充量和维持足够的转流流量是建立大鼠体外循环模型的关键。     

Proteasome inhibitor model of Parkinson's disease in mice is confounded by neurotoxicity of the ethanol vehicle.

Defects in the ubiquitin-proteasome system have been implicated in Parkinson's Disease (PD). Recently, a rat model of PD was developed using a synthetic proteasome inhibitor (PSI), (Z-lle-Glu(OtBu)-Ala-Leu-al). We attempted to transfer this model to mouse studies, where genetics can be more readily investigated due to the availability of genetically modified mice. We treated C57BL/6 (B6) mice with six intraperitoneal injections of 6 mg/kg PSI in 50 mul of 70% ethanol over a 2-week-period. We found significant decreases in nigrostriatal dopamine in PSI-treated mice compared with saline-treated mice. However, we observed similar decreases in the ethanol-treated vehicle control group. Administration of ethanol alone led to significant long-term alterations in dopamine levels. Ethanol significantly eclipses the effects of PSI in the dopamine system, and therefore is a confounding vehicle for this model.     

青少年精神分裂症患者家庭因素的研究

目的:探讨青少年精神分裂症患者的发病和家庭因素的相关性.方法:采用父母养育方式评价量表(EMBU)及家庭环境量表中文版(FES-CV)对60名青少年精神分裂症患者进行测评并与60名健康青少年进行对照及相关分析.结果:青少年精神分裂症患者父母养育方式与正常组对照显示:其父亲惩罚严厉、拒绝否认因子分显著高于对照组,情感温暖、理解因子分显著低于对照组(P＜0.05或P＜0.01);其母亲过分干涉过度保护、偏爱被试因子分显著高于对照组;母亲的情感温暖理解、过度保护、偏爱被试因子分高于父亲(P＜0.05或P＜0.01).家庭环境的亲密度、情感表达、文化性、娱乐性的因子分低于对照组,矛盾性和控制性均高于对照组(P＜0.05或P＜0.01).相关分析显示:父亲过度保护与母亲拒绝否认,及母亲过度保护与父亲拒绝否认因子之间呈负相关(r≥0.8);父亲与母亲EMBU相同因子得分具有相关关系(r≥0.6).结论:不良的家庭环境和父母养育方式对青少年精神分裂症的发病起一定作用,具有相关性.     

Establishment and characterization of a chronic infectious mononucleosislike syndrome in common marmosets

Epstein-Barr virus (EBV) was inoculated into two species of marmosets. Successful infection was established in the majority of the animals of one species, Callithrix jacchus, as evidenced by the development of high, persistent levels of antibody against virus-specific capsid and early nonstructural proteins. Antibodies also were produced against the major membrane antigen and, in some animals, against EBV nuclear antigen (EBNA) 2 but not against EBNA 1. This is the antibody profile normally noted in individuals with chronic infectious mononucleosis (IM). EBV-induced lymphoproliferation was not seen, and EBV-specific proteins were not detected in the peripheral blood lymphocytes of infected animals. Hence, EBV infection in C. jacchus apparently does not generally include extensive B-cell involvement. However, the marmosets clearly are useful as a model for EBV primary infection and also possibly for chronic IM.     

Understanding how Listeria monocytogenes targets and crosses host barriers

Human listeriosis is caused by the Gram-positive bacterium Listeria monocytogenes. In humans, this pathogen has the ability to cross the intestinal, placental and blood-brain barriers, leading to gastroenteritis, maternofetal infections and meningoencephalitis, respectively. The entry of L. monocytogenes into cultured human epithelial cells is mediated by the interaction of an L. monocytogenes surface protein, internalin, with its human receptor, E-cadherin. The internalin-E-cadherin interaction is species-specific, and relies on the nature of a single amino-acid in the E-cadherin molecule, which is proline in permissive species such as humans, and glutamic acid in non-permissive species such as the mouse. In a transgenic mouse model that expresses human E-cadherin in enterocytes, internalin allows L. monocytogenes to cross the intestinal barrier. Epidemiological evidence also supports a role for internalin in human listeriosis, not only for crossing the intestinal barrier, but also for targeting and crossing the placental and blood-brain barriers. Consistent with these epidemiological data, infection with L. monocytogenes of trophoblastic cell lines, primary trophoblast cultures and human placental villous explants demonstrates that bacterial invasion of the syncytiotrophoblast barrier is mediated by the internalin-E-cadherin interaction, leading to histopathological lesions that mimic those seen in the placentas of women with listeriosis. Thus, the internalin-E-cadherin interaction that plays a key role in the crossing of the intestinal barrier in humans is also exploited by L. monocytogenes to target and cross the placental barrier. Further investigations are currently focusing on the molecular mechanisms by which L. monocytogenes targets and crosses the blood-brain barrier.     

Animal study on the role of serotonin in depression

1. In our series of experiments the role of serotonin in human depression was studied by using animal models of depression.

2. The results of these studies support the hypothesis that some types of human depression may be primarily due to an excessive transmission of serotonin at the synapse.     

脱水穿心莲内酯珀琥酸半酯单钾盐家兔体内药代动力学实验研究

采用紫外分光光度法测定脱水穿心莲内酯琥珀酸半酯单钾盐血药浓度,并对腹腔单剂量注射给药后家兔体内药代动力学进行了研究。用计算机对血药时间数据进行了曲线拟合。结果表明:该药腹腔注射给药在家兔体内的转运符合二室开模型动力学方程。     

急性应激性溃疡模型的实验研究

本实验观察不同时间与方法所造成的应激性溃疡的模型。结果:禁食48小时,捆绑加浸水5小时,松绑后19小时,实验鼠胃粘膜出现多数病灶深、范围大、分布广的病灶,表现为出血、糜烂和溃疡,可谓最佳模型。     

Virulence of Candida albicans mutants

Mutant strains of the fungal pathogen Candida albicans blocked in pyrimidine transport and salvage metabolism were tested for virulence in various animal models. The growth rate, germination and proteolytic enzyme production did not correlate with the virulence of the strains. However, a defect in the uridine transport system significantly decreased virulence in murine candidosis, although it had no effect in vaginal candidosis or in a Candida cyst model. It remains unclear whether this is due to the differing host defence mechanisms involved in systemic and superficial mycoses, or to the different requirements of the fungal systems for adherence and tissue invasion in the two types of infection.     

Evidence for differential effects of 8-OH-DPAT on male and female rats in the Anxiety/Defense Test Battery

The Proxemics/Activity test and the Eat/Drink test, two components of the Anxiety/Defense Test Battery, were developed to measure defensive reactions to situations associated with a natural predator (cat). In the present studies the behavioral effects of 8-OH-DPAT treatment (0.01–1.0 mg/kg, SC) were entirely consistent with anxiety/fear reduction. These effects included an increase in time spent near the cat compartment, and a complimentary decrease in time spent farthest from this compartment, together with an increase in transits and locomote behavior. 8-OH-DPAT (1.0 mg/kg) also increased eat frequencies and durations (highly preferred food) both during and following cat presentation, without influencing drinking. This finding is discussed with reference to previous findings with 8-OH-DPAT in studies assessing both food intake and anxiolysis. Interestingly, 8-OH-DPAT was more potent in a majority of its effects in female subjects, a finding consistent with recent neurochemical data. These findings provide important behavioral evidence for a sexual differentiation in 5-HT function, and support the case for greater emphasis on female subjects in animal models of anxiety.Supported by NIH MH42803 and RCMI Grants RR03061 and RR01825