Mechanisms underlying the antidopaminergic effect of clonazepam and melatonin in striatum

Intrastriatal injection of the GABA_A antagonist, bicuculline, caused about a 75% decrease in the inhibitory effect of the central-type benzodiazepine (BZ) agonist, clonazepam or the indoleamine hormone, melatonin, on apomorphine-induced rotation in a 6-hydroxydopamine model of dopaminergic supersensitivity. Pretreatment with the peripheral-type BZ antagonist, PK 11195 (intrastriatally or intraperitoneally), also attenuated the antidopaminergic effect of these drugs but with much less potency than bicuculline. However, the combination of both bicuculline and PK 11195, injected directly into the striatum, completely blocked the antidopaminergic action of clonazepam or melatonin. These results indicate that the antidopaminergic action of clonazepam and melatonin in the striatum involves two distinct mechanisms: (1) a predominant GABAergic activation via the BZ/GABA_A receptor complex, and (2) a secondary mechanism linked to a PK 11195- sensitive BZ receptor pathway. Recent studies indicate that PK 11195 blocks BZ-induced inhibition of the adenylyl cyclase-cyclic AMP pathway in the striatum. Since cyclic AMP has been implicated in the rotational behaviour of 6-hydroxydopamine-lesioned animals, it is possible that the antidopaminergic action of clonazepam and melatonin also involves suppression of this second messenger. All rights reserved.     

Periodic alternating nystagmus and rebound nystagmus in spinocerebellar ataxia type 6.

We report on a family with ataxia type 6 (SCA6) showing peculiar oculomotor symptoms. The proband presented with periodic alternating nystagmus (PAN), and her 2 brothers had rebound nystagmus and gaze-evoked nystagmus. They carried the identical mutation (the number of expanded CAG repeat, 24) in the CACNA1A gene. The intrafamilial variability of oculomotor symptoms may be ascribed to factors other than CAG repeat expansion size in SCA6.     

D4S1647、D6S2414基因座在中国汉族、蒙古族、藏族的遗传多态性

目的 调查D4S1647、D6S2414基因座在中国汉族、蒙古族、藏族群体中的遗传分布规律。方法 采集308份血及唾液标本应用PCR技术，扩增产物用非变性聚丙酰胺凝胶电泳分离，银染显色分析。结果 两位点各群体基因型频率分布均符合Hardy-Weinberg平衡，每一位点等位基因频率分布在各群体间无显著差异；通过对10个汉族家系的遗传模式分析，证实了两位点等位基因传递遵循孟德尔遗传规律。结论 D4S1647、D6S2414基因座在中国汉族，蒙古族，藏族群体均具有高度遗传多态性。     

异丙酚对MPTP损伤的小鼠黑质多巴胺神经元的保护作用

目的　观察异丙酚对 1 甲基 4 苯基 1,2 ,3 ,6 四氢吡啶 (1 methyl 4 phenyl 1,2 ,3 ,6 tetrahydropyridineMPTP)损伤的小鼠纹状体多巴胺神经元的影响以及可能的作用机制。方法　给予Propofol 10 0mg/ (kg·d)后注射MPTP 2 0mg/ (kg·d) ,用药 6d。 12d后分离纹状体应用高效液相 -电化学方法检测纹状体多巴胺、二羟基苯乙酸及高香草酸的含量水平 ,应用12 5I- β-CIT放射性配基和免疫组化的方法检测多巴胺转运蛋白的活性和黑质神经元的损伤情况。结果　异丙酚可增加MPTP模型鼠多巴胺及其代谢产物的含量 ,异丙酚处理组DA ,DOPAC ,HVA的含量分别为 (8.2 417± 1.692 ) μg/ g、(1.3 81± 0 .486) μg/g和 (1.63 3 9± 0 .5 73 ) μg/ g ,与MPTP损伤组比较 ,明显增加。异丙酚亦可抑制黑质酪氨酸羟化酶 (TH)阳性神经元的减少。MPTP组注射MPTP 6d后 ,纹状体DAT为 (5 .3 13± 0 .64 2 )与正常组 (6.992± 0 .5 48) μg/ g比较显著下降 (P <0 .0 1) ,P +M组纹状体DAT为 (6.5 65± 0 .40 5 ) ,明显高于MPTP组 (P <0 .0 1) ,即减轻纹状体内多巴胺转运蛋白密度下降。结论　异丙酚对MPTP损伤的DA神经元具有一定的保护作用 ,其保护作用可能与抑制多巴胺转运蛋白活性有关     

利培酮治疗与细胞色素P4502D6/C188T酶基因多态性的关联分析

目的　研究利培酮临床效应的个体差异与其代谢酶细胞色素P4 5 0 2D6 (cytochromeP4 5 02D6 ,CYP2D6 )酶基因多态性的相关性。方法　对 88例符合CCMD 3精神分裂症诊断标准的患者和 96例健康对照者作病例 -对照分析。精神分裂症患者给予利培酮治疗 8周 ,用阳性和阴性症状量表 (posi tiveandnegativesymptomscale ,PANSS)评分评价利培酮疗效。采用聚合酶链反应扩增及限制性片段长度多态性 (PCR RFLP)技术对CYP2D6exonⅠ的C188T位点突变进行检测 ,分析利培酮临床效应与其主要代谢酶CYP2D6 /C188T酶基因多态性的相关性。结果　中国上海地区人群的CYP2D6 /C188T突变率(弱代谢型 )为 36 .3% ,病例组和正常对照组间基因型频率总体分布比较无显著差异 (χ2 =1.15 ,df=2 ,P >0 .0 5 ) ,两组间的等位基因频率之间比较也无显著性差异 (χ2 =0 .78,df=1,P >0 .0 5 )。进行性别及有否家族史分组后分析 ,亦无差异存在 ,且CYP2D6 /C188T突变与利培酮临床效应之间并无相关性 (χ2 =1.12 ,df=2 ;χ2 =0 .0 3,df=1,P >0 .0 5 )。结论　未发现中国人CYP2D6 /C188T多态性与利培酮临床效应的个体差异有相关性。     

Interactions Between Cytomegalovirus, Human Herpesvirus-6, and the Recurrence of Hepatitis C After Liver Transplantation

Recurrence of hepatitis C (HCV) following liver transplantation is common. Herpesvirus reactivation following transplant may have an immunomodulatory effect resulting in increased HCV replication. We studied whether cytomegalovirus (CMV) and human herpesvirus-6 (HHV-6) may be associated with HCV recurrence and viral load after transplant. We prospectively followed 66 HCV liver-transplant recipients with serial viral load testing for CMV and HHV-6. Infection and viral load were correlated with the development of biopsy-proven HCV recurrence and HCV viral loads. Histologic recurrence of HCV occurred in 41/66 (62.1%) patients. In the primary analysis, CMV infection and disease, and HHV-6 infection were not associated with HCV recurrence. Peak CMV and HHV-6 viral loads were not significantly different in patients with and without recurrence. No correlation was observed between HCV viral loads at 1 and 3 months post-transplant and peak HHV-6 or CMV viral loads. In a subgroup analysis, HHV-6 infection was associated with the development of more severe recurrence (hepatitis and/or fibrosis score > or = 2) (p = 0.01). Also, fibrosis scores at last follow up were higher in patients with CMV disease (1.67 vs. 0.56; p = 0.016) and in patients with HHV-6 infection (1.18 vs. 0.55; p = 0.031). In conclusion, HHV-6 and CMV infection and viral load were not associated with increased overall rates of HCV recurrence or HCV viral load after liver transplantation but may be associated with more severe forms of recurrence.     

骨感染病人TNF-α、IL-6和C反应蛋白的检测及临床意义

①目的　探讨骨感染病人肿瘤坏死因子α(TNF α)、白细胞介素 6 (IL 6 )和C反应蛋白 (CRP)水平的变化及意义。②方法　采用双抗体夹心ELISA法测定 30例骨感染病人及 2 5例正常人的血清TNF α、IL 6水平 ,采用散射比浊法测定CRP水平。③结果　骨感染病人血清中TNF α、IL 6及CRP含量均处于高水平状态 ,与健康人比较 ,差异有显著性 (t=2 .2 6～ 10 .6 7,P <0 .0 5、0 .0 1)。④结论　TNF α、IL 6及CRP是预测骨感染病人病情危重的重要指标之一 ,对临床有一定指导意义     

脉动真空灭菌器内室气体流向监测报警装置的研制

本文针对XGI型脉动真空灭菌柜出现的蒸汽倒流故障设计出一种内室气体流向监测报警装置，对管道中的蒸汽流向和空气流向进行监测。当出现倒流现象时，报警装置发出报警信号，提醒工作人员采取措施排除故障。经在两台灭菌柜上使用，证明此方案是一种行之有效的方法。     

Treatment of scleromyxoedema with hydroxychloroquine

Background: Scleromyxoedema is a rare disease of unknown aetiology that is characterized by deposition of mucin and sclerotic induration of the skin; it is associated with paraproteinaemia. Patients suffer from progressive disability due to immobilization and cosmetic disfigurement. Treatment of scleromyxoedema is a therapeutic challenge. The antimalarial hydroxychloroquine has a rapid and reliable effect in reticular erythematous mucinosis. Patients and methods: Four consecutive patients (two women, two men; median age: 50 years) with scleromyxoedema, three of them with IgG λ paraprotein, were treated with hydroxychloroquine. Treatment was initiated with 600 mg p. o. for 10 days, followed by 400 mg for at least 4 weeks, and 200 mg thereafter. Results: Complete remission of skin manifestations was achieved in one patient, whereas three patients achieved a partial remission of 61+, 5 and 25 months' duration. Notably, three patients felt increased mobility and reduced firmness of skin during the first week of treatment, which was reflected in a rapid reduction in dermal thickness. In one patient, dysphagia was reverted as evidenced by normalization of oesophageal clearance. Paraproteinaemia was not influenced at all. Side effects included one case of electroretinogram abnormalities after 19 months of therapy and one case of leucopenia after 3 months. Conclusion: Hydroxychloroquine is an effective form of therapy for scleromyxoedema, leading to rapid and prolonged alleviation of symptoms.