INVOLVEMENT OF NMDA RECEPTORS IN MORPHINE STATE–DEPENDENT LEARNING IN MICE

In the present study, the effects of intracerebroventricular (i.c.v.) injection of NMDA receptor agonist and antagonist on impairment of memory formation and the state-dependent learning by morphine have been investigated in mice. Pretraining administration of morphine (5 mg/kg; s.c.) decreased the learning of one-trial passive avoidance task. Pretest administration of morphine (5 mg/kg) induced state-dependent learning acquired under pretraining morphine influence. Pretest administration of NMDA receptor agonist, L-glutamate (0.00001 and 0.0001 and 0.001 μg/mouse, i.c.v.) following pretraining saline treatment did not affect retention. Amnesia induced by pretraining morphine was significantly reversed by pretest administration of L-glutamate (0.0001 and 0.001 μg/mouse, i.c.v.). Pretest administration of noncompetitive NMDA receptor antagonist, MK-801 (0.5, 1, and 2 μg/mouse, i.c.v.) significantly impaired memory formation. Amnesia induced by pretraining morphine was increased by pretest administration of MK-801 (2 μg/mouse, i.c.v.). Pretest coadministration of L-glutamate (0.0001 and 0.001 μg/mouse, i.c.v.) or MK-801 (0.5, 1, and 2 μg/mouse, i.c.v.) with morphine (5 mg/kg, s.c.) increased and decreased morphine state-dependent learning, respectively. The results suggest that NMDA receptors are involved in morphine state–dependent learning in mice.     

WHAT DEPRESSIVE SYMPTOMS ARE REPORTED IN ALZHEIMER'S PATIENTS?

Purpose. To ascertain the nature of depression-related symptoms in AD. Method. The Hamilton Rating Scale for Depression (HAM-D) was administered as a semi-structured interview to 30 consecutive Alzheimer's disease (AD) patients who also underwent independent psychiatric evaluation. The HAM-D was also administered with a caregiver as the informant. Results. There was no relationship between the number of symptoms reported by patients or caregivers and patients' level of cognitive impairment. Symptom reports by caregivers living in the same household did not differ significantly from symptom reports by caregivers living elsewhere. Caregivers rated AD patients as having significantly more depressive symptoms than did patients themselves. The items most frequently endorsed by caregivers were psychic anxiety (77%), suspiciousness (50%), low energy (50%) and depression (43%). The items most frequently endorsed by AD patients were weight loss (36%), psychic anxiety (33%) and somatic anxiety (33%). Depression was endorsed by 20% of patients. Caregiver-respondent HAM-D scores suggested clinically significant depression in 27% of cases, but AD patients' scores suggested clinically significant depression in only 7% of cases. No case of major depression was found on psychiatric examination. Conclusions. Depressive symptoms seemed more an executive function loss than of primary mood disturbance in that guilt, suicidal rumination and self-perceived loss of interest were uncommon, suggesting that simple environmental measures might be the most appropriate treatment of these symptoms.     

GROWING UP IN VIOLENT SITUATIONS—THE SOUTH AFRICAN SITUATION

Family predictors of tobacco and alcohol use were studied in random samples of school-going Black, Coloured, and White adolescents (total N=1,800) in the Cape Town Metropolitan Area. The subjects ranged in age from 14 to 17 years, with a mean age of 15.95 years. Logistic regression analysis of the data showed invariance across the three racial groups in terms of the specific family variables that were predictive, as well as their direction and magnitude of association with substance use. Essentially, higher rates of substance use for all three groups were predicted by parental behavioural control, parental monitoring/knowledge and limit setting, marital relations and family stress. The findings extend the work on South African adolescent substance use by providing a view into the proximal (family) socialising forces that are related to substance use. The findings also extend the broader work on identifying specialised effects of dimensions of socialization on adolescent functioning. The discussion section includes commentary on the cultural invariance found when measuring socialising forces at this level of generality.     

ACTIGRAPHIC EVIDENCE FOR NIGHT-TIME HYPERKINESIA IN PARKINSON’S DISEASE

Parkinson's disease is a common motor disorder that not only leads to motor symptoms but also autonomic dysregulation, mental changes, sensory disturbances, and sleep disorders such as increased daytime sleepiness and sleep fragmentation. The aim of this study was to find out how the daytime and night-time motor activity levels in individuals without motor disorders differ from patients with Parkinson's disease. Daytime and night-time motor activity levels in 17 PD patients and 69 controls were measured for three consecutive days and nights via actigraphy, a method of continuous long-term assessment of activity levels. A ratio between night-time and daytime motor activity was calculated. PD patients had a 1.5–2-fold lower daytime motor activity but also showed 1.5–2-fold higher motor activity at night time. Older controls showed a lower daytime but similar night-time motor activity when compared to younger controls. A ratio of night-time to daytime motor activity could clearly distinguish controls and patients. The possibility to distinguish patients and controls by the ratio of night-time to daytime motor activity is worth further investigation.     

HOW COMMON ARE THE ANXIETY DISORDERS IN OLD AGE?

This community study of the anxiety disorders in people aged 65 and over finds a relatively high prevalence of anxiety disorders (15%), with phobic disorders being the most prevalent subclassification (12%). While generalized anxiety was usually seen with other psychiatric syndromes, phobic disorder was usually observed in the absence of either depression or anxiety. These results suggest that while generalized anxiety should be placed below depression in a diagnostic hierarchy, phobic disorder does not fit with this diagnostic model.     

FoxP3+ CD4+ CD25+调节性T细胞在重症肌无力发病机制中的作用

目的 在细胞与分子水平检验重症肌无力(myasthenia gravis,MG)患者外周血中CD4+CD25+调节性T细胞(CD4+CD25+Tregs)的表达缺陷,探讨CD4+CD25+Tregs亚群异常与MG发病间的关系.方法 流式细胞技术检测21例MG患者(11例经胸腺切除)与20名健康对照者(healthy controls,HCs)外周血CD4+CD25+Tregs及FoxP3+CD4+CD25+Tregs含量,实时荧光定量聚合酶链反应(RT-FQ-PCR)分析MG患者与HCs外周血CD4+CD25+Tregs中FoxP3 mRNA的表达.结果 MG患者外周血CD4+CD25+ Tregs占CD4+T细胞含量与HCs比较无统计学差异(P＞0.05).MG患者外周血FoxP3+CD4+CD25+ Tregs含量及FoxP3 mRNA表达量与HCs比较均显著性降低(P＜0.05);胸腺切除的MG患者与未经胸腺切除的MG患者外周血FoxP3+CD4+CD25+ Tregs含量及FoxP3mRNA表达量无统计学差异(P＞0.05).结论 MG患者外周血CD4+CD25+ Tregs数量正常,但其表面分子FoxP3的表达下调,这种CD4+CD25+ Tregs亚群的异常发现有助于深入阐明MG的免疫发病机制.     

AUTOANTIBODIES IN MULTIPLE SCLEROSIS, AND THEIR ASSOCIATION WITH THERAPY

Background: Humoral autoimmunity, in patients with hepatitis and Multiple Sclerosis, during interferon therapy , is often asymptomatic and transient. This suggested that it was a finding present in MS patients independently from therapy. Objective: In our paper we analyze the positivity to any antibody, to clarify whether it is modified by immunomodulating therapy. Design: It is an observational study, in which the frequency of positivity was calculated in the patients grouped for sex, multiple sclerosis clinical parameters, MRI features, and disease modifying therapy. Setting: The study took place in the Neurology Unit where our Multiple Sclerosis Center is located. Our MS patients, mostly outpatients, are usually tested yearly for several autoantibodies: against Cell Nuclei (ANA), dsDNA, Cardiolipin (ACL, IgM and IgG), Thyroid Antigens (antiperoxydase, TPO), Mithocondria (AMA), Smooth Muscle (ASMA), Parietal Cells (APCA) , Rheumatoid Factor. Participants: 169 MS patients were included, 57 males, 112 females, age between 11-59 yrs, mean 29.39; 136 of them suffered from relapsing-remitting disease; 33 were in secondary progressive stage. Patients with previous immunological diseases were excluded from statistical evaluation. In this paper 2005, 2006 and 2007 data are collected. The study, though planned prospectically, is retrospective. Interventions: 113 patients treated with beta Interferons (IFNs), 18 copolimer (COP): 8 mitoxantrone (MIX): 5 azathioprine (AZA): 3 interferon and AZA in association; 18 not treated. Outcomes: Frequency of positivity to any autoantibody (at least one test). Prevalences and incidences were calculated. Crosstabulations with odds ratios and chi-square were used to test frequencies, for more variables multiple regression was used. Also “person-year” data, for a crude total of 466 “person-years”, are calculated. Results: 3395 tests were performed. The overall prevalence in the 3 years was 47,3% (79/167, c.i. 40,2-55,2). In patients untreated or treated with drugs different from IFNs (COP, MIX, AZA), the prevalence is 23,2% (10 on 43). With interferons it is 55.6% (69/124). Annual incidence (patients already treated), is 6,3% (7/111) significantly higher in females. Greater differences are seen comparing the groups treated with IFNs (104/205) versus different drugs, or no treatment (15/85) (OR= 2,87 (95%CI=1,5-5,2); p=0.0001). Multiple regression show significant association of the autoantibodies with IFN 1a, either im (p=0.002) or sc (p=0.03). Similar results are seen for antithyroid antibodies, significantly associated with interferons (p=0,0004), and more prevalent in females (33,3% vs 18,9%). Nevertheless, multiple regression for the main variables (sex, IFN therapy, relapses, MRI), is significant only for the therapy. Conclusions: Interferon therapy is associated with significantly increased frequency of autoantibodies in patients with multiple sclerosis.The differences among the therapies are not influenced by other variables as sex or clinical pattern. However, in most patients no autoimmune disease is diagnosed, except for thyroiditis, as already reported in previous literature.     

CD4+CD25+ T细胞的扩增及其功能分析*☆

背景：CD4+CD25+ T细胞增殖能力低,且在人外周血中仅占单个核细胞的4%左右。若能在体外高效扩增CD4+CD25+ T细胞,并保持其免疫调节特性,将会对临床移植产生积极的影响。 目的：观察C57BL/6小鼠来源的CD4+CD25+ T细胞体外增殖情况及其扩增后的功能变化。 设计、时间及地点：细胞学体外观察,于2007-10/2008-05在南方医科大学珠江医院血液科完成。 材料：SPF级C57BL/6及BALB/C雄性小鼠购自南方医科大学动物所。小鼠白血病细胞EL9611由珠江医院血液科惠赠。 方法：利用免疫磁珠法分选小鼠CD4+CD25+ T细胞;以抗鼠 CD3ε单抗、抗鼠CD28单抗、鼠重组白细胞介素2及辐射过的BALB/C小鼠脾细胞为共刺激因子,通过实时定量RT-PCR检测扩增后CD4+CD25+ T细胞FoxP3基因mRNA表达变化,以确定增殖效率;3H-TdR掺入法检测扩增后的CD4+CD25+ T细胞对CD4+CD25-T细胞增殖的影响;LDH释放法检测扩增后的CD4+CD25+ T细胞对CD4+CD25-T细胞杀伤小鼠白血病细胞EL9611的影响,以CD4+CD25-T细胞为效应细胞,以EL9611细胞为靶细胞。 结果：经免疫磁珠分选可获得高纯度及较强活性的CD4+CD25+ T细胞。扩增后CD4+CD25+T细胞FoxP3基因mRNA的表达平均为扩增前的5.46倍,最高可达14.39倍。扩增后CD4+CD25+T细胞可明显抑制CD4+CD25-T细胞的增殖,且随着CD4+CD25+T细胞数的增加,这种抑制增殖的能力也逐渐增强,当两者比例为1:1时抑制率最大,达62.05%。与单纯CD4+CD25- T细胞对EL9611细胞杀伤率比较,效靶比为10:1时扩增后的CD4+CD25+ T细胞联合CD4+CD25- T细胞的杀伤率无明显变化（t=2.199,P > 0.05）;效靶比为5:1时扩增后的CD4+CD25+ T细胞联合CD4+CD25- T细胞的杀伤率则明显降低（t=5.839,P < 0.05）。 结论：单抗加异源性抗原能有效扩增CD4+CD25+T细胞;扩增后的CD4+CD25+T细胞比新鲜分离的CD4+CD25+T细胞能更有效地抑制CD4+CD25-T细胞的增殖,其对CD4+CD25-T细胞杀伤白血病细胞的作用则取决于其与CD4+CD25-T细胞的相对比例。     

IMPACT OF DIFFERENT INJURY SITES IN S-D RATS’ OCULOMOTOR NERVES

目的：研究不同部位损伤对Sprague-Dawley(以下简称S-D)大鼠动眼神经功能修复的影响及可能机制。方法：经幕下和眶上裂切断和修复动眼神经，术后通过前庭眼反射评估眼外肌在垂直、水平方向的恢复程度，经右侧上直肌注射HRP逆行追踪中脑动眼神经核团内神经元分布，动眼神经组织学、解剖学研究。结果：经眶上裂干预动眼神经的实验组大鼠新生神经纤维对眼外肌支配的特异性较高，其眼外肌功能恢复程度明显优于经幕下干预动眼神经的实验组大鼠。结论：动眼神经损伤部位距离眼外肌越近，最终的神经功能恢复水平就越好，其机理可能与再生神经纤维通过损伤部位时的迷行程度有关。     

PERIFASCICULAR EXPRESSION OF THE NEURAL CELL ADHESION MOLECULE IN INTERSTITIAL MYOSITIS

（１）目的：突发性多发性肌炎（ＩＰＭ）、皮肌炎（ＤＭ）和包含体肌炎（ＩＢＭ）在形态学上定义明确，但仅有间质性肌炎的诊断标准不够明确。为了确定ＩＢＭ形态学上的特征，作者用光镜试图探索肌纤维束周Ｌｅｕ１９抗原表达对ＩＢＭ的诊断意义。（２）方法：１５例无肌无力的正常对照，１２例ＩＰＭ，１４例ＤＭ，２６例ＩＢＭ，８例坏死性血管炎（ＮＶ），１５例神经性肌萎缩（ＮＭ），作肌肉活检。除作常规光镜检查外，还作免疫组化研究，用小鼠抗Ｌｅｕ１９、Ｌｅｕ２ａ、ＣＤ４、ＣＤ１６、ＣＤ２２、ＣＤ６８、Ｃ５ｂ－９单克隆抗体作一抗，再用碱性磷酸酶抗碱性磷酸酶法显色。（３）结果：肌纤维束周Ｌｅｕ１９抗原表达阳性率：ＩＢＤ、ＤＭ和ＮＶ依次为８５％、１００％和１００％，而正常对照、ＮＭ均为０％。（４）结论：在其它方面正常而有肌纤维束周Ｌｅｕ１９抗原表达是ＩＢＭ的病理学特征，所以可能有诊断价值。     

COMPUTED TOMOGRAPHIC GUIDANCE STEREOTAXIS IN THE MANAGEMENT OF INTRACRANIAL MASS LESIONS

The stereotactic neurosurgical resection,which was named by the greek word(?),began with the pioneering publica-tion of Horsley and Clarke in 1908.The ad-vent of computed axial tomography has notonly provided new insights into intracranialdisease,but has also investigated in applying     

供体凋亡淋巴细胞预输注对猪肝移植受体CD4+T、CD8+T、CD4+CD25+调节性T细胞的影响

背景：凋亡细胞能够主动调节机体的免疫功能,并能通过调节机体细胞免疫和体液免疫的途径诱导免疫耐受,但这些结果只在大鼠肝脏移植模型中证实。 目的：探讨通过60Co γ射线体外处理后的供体淋巴细胞预输注诱导猪肝移植特异性免疫耐受的作用中,对淋巴细胞亚群的影响。 方法：建立非转流小型猪原位肝移植模型。将受体猪随机摸球法均分为2组：空白对照组,受体猪无特殊处理,行肝移植;淋巴细胞组：受体猪在肝移植前7 d经耳静脉注射60Co γ射线处理过的5×108个供体淋巴细胞。观察两组受体猪移植后的存活时间,移植后T淋巴细胞亚型CD4+T、CD8+T、CD4+CD25+Tr变化及病理。 结果与结论：移植后3 d,两组病理活检均呈急性中、重度排斥反应;移植后6 d,两组均呈急性重度排斥反应。移植后1,3,6 d CD4+T、CD8+T、CD4+CD25+Tr升降趋势,两组间差异无显著意义(P > 0.05)。提示,60Co γ射线体外处理过的淋巴细胞预输注未能够诱导猪同种异体肝移植特异性免疫耐受,未能引起T淋巴细胞亚群变化有关。     

骨骼肌肌浆网Na+，K+-ATP酶和Ca2+-ATP酶活性在不同训练条件下的变化

背景：Na+,K+-ATP酶和Ca2+-ATP酶在物质运送、能量转换以及信息传递方面具有重要作用。肌浆网在肌肉兴奋-收缩耦联过程中起关键作用,与运动性骨骼肌疲劳的发生密切关。 目的：通过建立SD大鼠有氧和无氧训练模型,观察不同训练负荷条件对大鼠骨骼肌肌浆网Na+,K+-ATP酶和Ca2+-ATP酶活性的影响。 方法：参照Bedford TG标准,建立有氧和无氧运动大鼠跑台训练模型,有氧运动组采用递增负荷训练,无氧运动组采用高速间歇训练,正常对照组大鼠正常笼内生活,不运动。各组动物训练结束后用超速离心法提取大鼠骨骼肌肌浆网,紫外分光光度计检测大鼠骨骼肌肌浆网Na+,K+-ATP酶和Ca2+-ATP酶的活性。 结果与结论：训练4周后,两个运动组大鼠骨骼肌肌浆网Na+,K+-ATP酶和Ca2+-ATP酶的活性逐渐升高(P < 0.05);训练6周,仅有氧运动组升高(P < 0.05),无氧运动组则活性降低(P < 0.05)。结果提示有氧训练更有利于保护大鼠骨骼肌肌浆网Na+,K+-ATP酶和Ca2+-ATP酶的活性,但需要一定的时间累积。     

Reduced circulating CD4+CD25+ cell populations in Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is a monophasic inflammatory disease considered to be due to autoimmunity. In order to test the hypothesis that the disease is associated with a perturbation of the circulating lymphoid cell population, we tested the mononuclear cells from the venous blood of 21 patients with Guillain-Barré syndrome (GBS) and 20 healthy controls by flow cytometry. The proportions and numbers of B and T lymphocytes, and CD4, CD8, double negative and gammadelta T cell subsets and numbers of monocytes were not significantly different in the patients compared with the controls. However, the number and proportion of CD4+CD25+ cells were reduced in acute GBS (mean number 61.7 cells/microl, 95% CI 42.9-80.4 and mean percentage 4.6%, 95% CI 3.8-5.4) compared with controls (mean number 99.8 cells/microl, 95% CI 74.7-124.9, p=0.02, and mean percentage 6.0%, 95% CI 4.9-7.1%, p=0.037). In addition, in GBS patients, the number and proportion of CD4+ T cells expressing CD25+ and HLA-DP, DQ, DR (mean number 11.9 cells/microl, 95% CI 7.6-16.1 and mean percentage 0.8%, 95% CI 0.5-1.1%) was lower than in healthy controls (23.5 cells/microl, 95% CI 16.4-30.6, p=0.01, and mean percentage 1.4%, 95% CI 1.1-1.8%, p=0.005. Since CD4+CD25+ cells include cells with special immunoregulatory functions, further investigation of this phenomenon and its relation to possible loss of regulatory T cell function in GBS is warranted.     

有氧运动对大鼠骨骼肌线粒体Na+，K+-ATP酶和Ca2+-ATP酶及线粒体肿胀的影响

背景：研究表明有氧运动可提高线粒体功能,但在不同时期的作用特点还不明确。 目的：观察不同周期有氧运动对大鼠骨骼肌线粒体Na+,K+-ATP酶和Ca2+-ATP酶以及线粒体肿胀的影响。 方法：将SD大鼠随机分为正常对照组,有氧运动2,4和6周组。正常对照组不进行有氧运动,其余3组则参照BedfordTG标准,采用跑台运动方式,建立有氧运动模型进行相应的运动周期锻炼。测定各组大鼠骨骼肌线粒体Na+,K+-ATP酶和Ca2+-ATP酶的活性以及线粒体肿胀程度。 结果与结论：有氧运动2周组各指标与对照组比较无差异。有氧运动4和6周组线粒体Na+,K+-ATP酶、Ca2+-ATP酶活性均增高(P < 0.05),线粒体肿胀程度降低(P < 0.05)。实验结果表明,有氧运动可保护线粒体Na+,K+-ATP酶、Ca2+-ATP酶的活性,提高线粒体功能,但需要一定的时间积累。