Ethyl-EPA in Huntington disease—Potentially relevant mechanism of action

The pathomechanisms involved in the neuronal dysfunction in Huntington disease (HD) are still unresolved and may be heterogeneous. One potential mechanism might be related to the induction of mitochondrial dysfunction in the CNS. This might lead firstly to neuronal dysfunction and finally to the activation of apoptotic pathways. Several compounds, which should alleviate mitochondrial dysfunction, have been tested in preclinical models as well as in clinical trials of different scale. Recently we reported the efficacy of Ethyl-eicosapentaenoic acid (Ethyl-EPA) in patients with HD. Ethyl-EPA is a polyunsaturated fatty acid from the n − 3 group, which is in clinical development for HD and melancholic depression. In our trial with Ethyl-EPA in HD responding patients could be characterized by either a lower CAG repeat number or a chorea-predominant clinical expression of the disease. Here we would like to describe some evidence on the potential mechanism of action of Ethyl-EPA in HD. We specifically focus on pathways, which are known to be influenced in HD and are modified by Ethyl-EPA and which points to an involvement of mitochondrial function as a common target. Some attention is given to the NF-kappa B pathway and the c-Jun amino-terminal kinases (JNK) pathway, which both may lead to an activation of the antiproliferative factor p53 and consequently mitochondrial dysfunction. Further the effects of EPA or Ethyl-EPA in preclinical models of HD are described. The evidence from these studies led to the design of phase III clinical trials, which are ongoing.     

外消旋聚乳酸复合神经生长因子缓释导管促周围神经再生的形态学研究

目的 建立外消旋聚乳酸复合神经生长因子（poly-D，L-lactic acid／nerve growth factor，PDLLA／NGF）可吸收性缓释导管桥接修复大鼠坐骨神经缺损的动物模型，观察复合导管对大鼠坐骨神经缺损再生的促进作用。方法利用溶剂挥发法制备PDLLA单纯导管和PDLLA／NGF缓释导管，每根缓释导管含NGF450U。SD大鼠40只随机分成4组，每组10只，切除中段坐骨神经10mm之后分别行自体神经移植（A组）、单纯导管桥接（B组）、单纯导管加一次性给药（C组）、PDLLA／NGF缓释导管桥接（D组）修复坐骨神经，除A组外，均保留10mm缺损。术后3个月观察神经再生情况，比较各组光镜、电镜及图像分析等指标。结果术后3个月导管与周围组织粘连松，并开始降解，但外形仍保持完整。再生神经均顺利通过导管腔，组织学观察A组和D组内神经纤维数目多，大小均匀，成熟良好；B组和C组纤维结缔组织多，神经纤维细小，髓鞘薄。图像分析显示除神经纤维计数D组高于A组外，A组和D组在纤维直径、轴突直径和髓鞘厚度方面差异均无统计学意义（P〉0．05），并明显优于B组和C组（P〈0．05）。结论 PDLLA／NGF缓释导管能够有效促进大鼠坐骨神经缺损再生，组织学观察指标接近自体神经移植。     

高果糖诱导IR大鼠模型血清脂质代谢的改变及意义

目的: 评估高果糖膳食对机体胰岛素敏感性及血清脂质代谢的影响及意义.方法:以高果糖膳食(果糖占总热量34.5%)诱导并经钳夹技术证实建立胰岛素抵抗(IR)大鼠模型,生化比色法测定血清游离脂肪酸(FFA),生化酶法测定血清甘油三酯(TG)及总胆固醇(TC).结果:高果糖膳食喂养4周后,实验组大鼠葡萄糖输注率由(11.5±0.6)mg/kg·min-1下降至(6.6±0.4)mg/kg·min-1(P<0.01);血清FFA由(0.45±0.09)mmol/L增至(0.78±0.19)mmol/L(P<0.01);TG由(0.54±0.10)mmol/L增至(0.96±0.22)mmol/L(P<0.01);TC由(1.96±0.32)mmol/L增至(2.42±0.21)mmol/L(P<0.01).结论:高果糖膳食可导致机体严重IR,是建立IR大鼠模型的有效手段;该模型同时伴有血清脂代谢各相关指标的明显异常,血脂的变化既是IR的结果,也是IR向纵深发展的原因和必要条件.     

Proline reduces brain cytochrome c oxidase: prevention by antioxidants

In the present study, we initially investigated the in vivo (acute and chronic) and in vitro effects of proline on cytochrome c oxidase (complex IV) activity in rat cerebral cortex to test the hypothesis that proline might alter energy metabolism and that this alteration could be provoked by oxidative stress. The action of alpha-tocopherol and ascorbic acid on the effects produced by proline was also evaluated. For acute administration, 29- and 60-day-old rats received one subcutaneous injection of proline (18.2 micromol/g body weight) or an equivalent volume of 0.9% saline solution (control) and were sacrificed 1h later. For chronic treatment, proline was injected subcutaneously twice a day at 10h intervals from the 6(th) to the 28(th) day of age. Rats were sacrificed 12h (29(th)) or 31 days (60(th)) after the last injection. Results showed that acute administration of proline significantly diminished the activity of cytochrome c oxidase in the cerebral cortex of 29- and 60-day-old rats. On the other hand, chronic hyperprolinemia reduced this complex activity only on day 29, but not on the 60(th) day of life. In another set of experiments, 22-day-old rats or 53-day-old rats were pretreated for 1 week with daily intraperitoneal administration of alpha-tocopherol (40 mg/kg) and ascorbic acid (100mg/kg) or saline. Twelve hours after the last antioxidant injection, rats received a single injection of proline or saline and were killed 1h later. In parallel to chronic treatment, rats received a daily intraperitoneal injection of alpha-tocopherol and ascorbic acid from the 6(th) to the 28(th) day of life and were killed 12h after the last injection. Results showed that the pretreatment with alpha-tocopherol and ascorbic acid before acute proline administration or concomitant to chronic proline administration significantly prevented these effects. We also observed that proline (3.0 microM-1.0 mM) when added to the incubation medium (in vitro studies) did not alter cytochrome c oxidase activity. Data suggest that the inhibitory effect of proline on cytochrome c oxidase activity is possibly associated with oxidative stress and that this parameter may be involved in the brain dysfunction observed in hyperprolinemia.     

人抵抗素基因cDNA的克隆

目的克隆人抵抗素基因(hRETN)cDNA,为进一步研究RETN的结构和功能提供实验基础.方法应用RT-PCR方法从中国人网膜脂肪垫总RNA中扩增出RETN 基因cDNA,克隆入载体pMD18-T中,形成重组载体pMD18-T/hRETN.通过蓝白斑筛选出阳性克隆,限制性内切酶酶切鉴定后对其进行测序.结果从脂肪组织总RNA中扩增得到363 bp片段hRETN基因,其cDNA序列与Genbank hRETN基因序列基本相同.结论成功地克隆中国人hRETN cDNA.     

参麦注射液治疗心绞痛的临床观察

目的　探讨参麦注射液对冠心病 (CHD)心绞痛的治疗作用。方法　 80例患者分为两组 ,每组 4 0例 ,在常规治疗的基础上 ,对照组应用丹参注射液进行治疗 ,治疗组应用参麦注射液进行治疗。结果　治疗组有效 39例 (97.5 % ) ,心电图改善 38例 (95 .0 % ) ,对照组分别为 31例 (77.5 % )和 2 9例 (72 .5 % ) ,组间比较具有显著性差异 (P <0 .0 1)。结论　参麦注射液对冠心病心绞痛疗效显著 ,且安全、无明显副作用     

复方麝香注射液联合脑血肿引流术治疗中老年高血压脑出血疗效观察及费用对比

目的:探讨复方麝香注射液联合微创手术治疗中老年高血压脑出血的临床疗效.方法:将78例接受微创治疗的患者随机分组,两组均采用内科综合治疗.手术对照组在综合治疗基础上加用微创手术进行脑血肿引流;中西医结合组在微创手术治疗后加用复方麝香注射液(10～20 ml/d)静脉滴注1周.结果:中西医结合组显效率(66.67%)、有效率(82.05%)均明显高于手术对照组(46.15%和69.23%,P均<0.05),存活患者日常生活能力也明显优于手术对照组(P<0.05),意识恢复时间明显短于手术对照组(P<0.05),并发症的发生率(15.38%)明显低于手术对照组(38.46%,P<0.01),病死率(5.13%)明显低于手术对照组(10.26%,P<0.01),平均住院天数[(18.29±4.93)d]明显少于手术对照组[(26.23±5.82)d,P<0.05],平均住院费用[(5 916.23±826.39)元]明显少于手术对照组[(8 168.35±1 021.21)元,P<0.05].结论:脑血肿引流术后加用复方麝香注射液治疗中老年高血压脑出血,可降低病死率,减少并发症,降低病残程度,提高生存患者的生活质量,缩短住院时间,降低治疗费用.     

ATP下鼻甲注射治疗药物性鼻炎的价值

目的 探讨ATP下鼻甲注射治疗药物性鼻炎的价值,并对ATP治疗药物性鼻炎的机理进行分析。方法 对80例采用ATP下鼻甲注射治疗(ATP组)与40例采用激光治疗(激光组)作疗效比较。结果 ATP组有效率(95％),与激光组(100％),疗效相当,无显著性差异(P>0.05)。结论ATP下鼻甲注射治疗药物性鼻炎疗效佳,起效快,痛苦小,简便易行,费用低廉,且无毒、副作用,值得推广。     

A prospective study of the association of cerebrospinal fluid monoamine metabolite levels with lethality of suicide attempts in patients with bipolar disorder

Objectives:  Bipolar disorder is a severe illness that is associated with suicidal behavior. A biological predictor of highly lethal suicide attempts in patients with bipolar disorder would be valuable. We hypothesized that cerebrospinal fluid (CSF) monoamine metabolite levels are related to lethality of suicide attempts in bipolar patients and examined the relation between CSF 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and maximum lethality of suicide attempts at baseline and during a 2-year follow up.
Methods:  Twenty-seven bipolar depressed patients participated in the study. Demographic and clinical parameters were examined and recorded. Lumbar punctures were performed and CSF 5-HIAA, HVA, and MHPG were assayed by high-performance liquid chromatography with electrochemical detection. Following discharge, patients were evaluated after 3 months, 1 year, and 2 years. Each follow-up interview included an in-depth assessment of suicidal behavior during the intervening time period.
Results:  Six subjects made suicide attempts during the 2-year follow-up. Bipolar patients who attempted suicide during the follow-up period had higher aggression and hostility scale scores compared to bipolar subjects who did not make a suicide attempt during the follow-up period. CSF 5-HIAA, HVA, and MHPG levels were negatively correlated with the maximum lethality of suicide attempts during the 2-year follow-up period.
Conclusions:  Our finding is the first observation that CSF monoamine metabolite levels may be predictors of lethality of suicide attempts in patients with bipolar disorder. Further studies are necessary to answer the question whether CSF monoamine metabolite levels are clinically useful biochemical predictors of highly lethal suicide attempts or completed suicides.     

齐墩果酸免疫治疗恶性肿瘤病人的临床Ⅱ期研究

前瞻性双盲法临床研究,可评价的恶性肿瘤病人28例,口服齐墩果酸40mg,每日3次,1个月后测定吞噬细胞百分比,由54.1％提高至67.42％。吞噬指数由0.69提高至0.81。迟发超敏反应1:1000浓度转阳性率52.6％(10/19)。E-玫瑰花结试验在本组试验前后无显著变化。同期服用安慰剂的9例对照病人则无变化。治疗后齐墩果酸对骨髓、肝、肾功能均无影响,故可做为比较理想的生物反应调节剂应用于临床,以促进病人的免疫功能。