Open, Double-Blind and Long-Term Study of Vigabatrin in Chronic Epilepsy

We performed an open, double-blind, and long-term study of vigabatrin (gamma-vinyl-GABA, GVG) in patients with treatment-resistant epilepsy who were receiving only one or at most two standard antiepileptic drugs (AEDs). The novel design included a parallel, double-blind, placebo-controlled phase that minimized the number of patients receiving placebo and allowed determination of the optimum dose of GVG for each patient before initiation of the double-blind phase. The study was divided into four phases. The first phase was a 6-week period of baseline observation. In the second phase, GVG was added openly to previous AEDs for 8 weeks. During the first 2 weeks of this phase, the dose of GVG was increased weekly and then, in the absence of adverse effects, was held constant for the next 6 weeks. At the end of this open phase, seizure frequency during the 6 weeks of constant treatment was compared with the baseline seizure frequency for each patient. Patients who experienced reduction greater than 50% in the frequency of any seizure type during the open phase were defined as responders. These responders were then entered into the third and double-blind phase, in which they were randomly allocated wither to continue active GVG treatment or placebo for 8 weeks. Thirty-three patients entered the study; 31 of 33 patients completed the initial open phase. Twenty patients achieved a reduction greater than or equal to 50% in the frequency of one or more seizure types and were eligible for the double-blind phase; 10 were randomized to continue GVG and 10 were randomized to placebo.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of mattress characteristics on house dust mite allergen concentration

BACKGROUND: Exposure to a high level of house dust mite allergens (HDMAs) is considered as a risk factor for HDM sensitization and development of asthma in genetically disposed people. Mattresses are one of the most important sources of HDMA in people's living environment. OBJECTIVE: The aim of this study was to evaluate the association between mattress characteristics and HDMA concentrations on mattresses. METHODS: Dust samples of mattress surfaces were taken to evaluate the level of Der p 1 allergen. All participants filled in a questionnaire about the type of mattress, the type of covering (upper layer) of the mattress, dwelling characteristics and cleaning habits. Humidity and temperature of the bedroom were measured at the time of dust sampling. RESULTS: One hundred and sixty-eight questionnaires were filled in. Synthetic upper layer of the mattress was associated with a higher level of Der p 1 compared with cotton upper layer (2.6 vs. 0.8 microg/g Der p 1). Moreover, higher relative humidity (RH) was associated with significant higher concentrations and density of Der p 1. CONCLUSIONS: Two factors were associated with lower levels of Der p 1 found on mattresses, namely: a cotton upper layer of the mattress compared with a layer of synthetic material and lower RH at the time of sampling. As far as we know, the association between type of upper layer and concentration of Der p 1 has not been described before and could lead to the formulation of practical advices in order to reduce HDMA concentrations on mattresses.     

Expression of Anion Exchanger 1 Sequestrates p16 in the Cytoplasm in Gastric and Colonic Adenocarcinoma

p16^INK4A (p16) binds to cyclin-dependent kinase 4/6 and negatively regulates cell growth. Recent studies have led to an understanding of additional biologic functions for p16; however, the detailed mechanisms involved are still elusive. In this article, we show an unexpected expression of anion exchanger 1 (AE1) in the cytoplasm in poorly and moderately differentiated gastric and colonic adenocarcinoma cells and in its interaction with p16, thereby sequestrating the protein in the cytoplasm. Genetic alterations of p16 and AE1 were not detectable. Forced expression of AE1 in these cells sequestrated more p16 in the cytoplasm, whereas small interfering RNA-mediated silencing of AE1 in the cells induced the release of p16 from the cytoplasm to the nucleus, leading to cell death and growth inhibition of tumor cells. By analyzing tissue samples obtained from patients with gastric and colonic cancers, we found that 83.33% of gastric cancers and 56.52% of colonic cancers coexpressed AE1 and p16 in the cytoplasm. We conclude that AE1 plays a crucial role in the pathogenesis of gastric and colonic adenocarcinoma and that p16 dysfunction is a novel pathway of carcinogenesis.     

外源性p53对不同LET辐射诱导人黑色素瘤细胞系A375死亡途径的影响

目的 观察外源性P53蛋白对不同传能线密度(LET)射线辐照诱导肿瘤细胞凋亡和坏死的影响,并探讨其可能的机制。方法 人黑色素瘤细胞系A375(wild-type p53)经携带人野生型p53基因的腺病毒载体(AdCMV-p53)感染后分别给予X射线和碳离子束照射,采用克隆形成法测定细胞辐射敏感性,Hoechst 33258和吖啶橙-溴化乙锭双染荧光显微镜下观察细胞凋亡和坏死。结果1高LET辐照时,A375细胞和转导人野生型p53基因的A375细胞(A375/p53)的辐射敏感性没有明显差异;2虽然辐射诱导细胞凋亡比例的增加依赖于LET升高,但是无论高LET或低LET,外源性P53蛋白均可有效诱导细胞凋亡。3高LET辐照时,A375细胞的坏死细胞明显高于A375/p53细胞。结论 尽管高LET辐射对A375和A375/p53细胞的存活无明显影响,但是对细胞凋亡的诱导却部分依赖于P53蛋白的功能,P53蛋白可能在调节细胞死亡类型中发挥重要作用。这对临床应用高LET辐射联合p53基因治疗恶性黑色素瘤有一定参考意义。     

17 β雌二醇通过丝裂原活化蛋白激酶抑制前列腺癌细胞系PC3增殖

目的探讨丝裂原活化蛋白激酶在17β雌二醇(E2)抑制前列腺癌PC3细胞生长中的作用。方法检测不同浓度E2作用不同时间后PC3细胞生长抑制率。流式细胞仪分析细胞周期分布,TUNEL染色检测凋亡。Western blot检测ERK1/2,JNK和p38活性。RT-PCR法检测雌激素受体(ER)α、ERβ、P21WAF1和cyclinD1的表达。结果E2抑制PC3细胞增殖,并且可以激活ERK1/2、JNK和p38。处理因素作用48h后,对照组、E2、E2 PD98059、E2 SP600125、E2 SB203580组细胞的凋亡率分别为(0.9±0.1)%;(23.0±1.4)%;(30.0±1.2)%;(10.6±0.8)%和(14.6±0.7)%,(P<0.05)。E2使细胞阻滞在G1期,PD98059、SP600125、SB203580分别预处理1h后细胞分别进一步阻滞在G1期;轻度阻滞在G1期和进入S期。RT-PCR发现PC3细胞表达ERα和ERβ,E2、E2 PD98059、E2 SP600125、E2 SB203580组中cyclinD1、P21WAF1基因表达分别为对照组的(0.42±0.03)、(3.13±0.02)倍;(0.21±0.03)、(3.08±0.05)倍;(0.43±0.01)、(1.31±0.04)倍;(2.81±0.02)、(3.14±0.02)倍(P<0.05)。结论E2激活JNK增加P21WAF1基因表达,并激活p38抑制cyclinD1表达,使细胞阻滞在G1期,JNK和p38通路还介导E2引起PC3细胞凋亡。同时E2又可激活ERK1/2,轻度拮抗上述作用。     

胰腺癌中p16基因甲基化改变及其蛋白表达分析

目的:探讨胰腺癌与癌旁组织中p16基因启动子区异常甲基化的改变及其蛋白表达的特点,以及其与胰腺癌发生发展的关系。方法:分别采用免疫组化SP法及甲基化特异PCR(MSP)检测46例人胰腺癌和癌旁组织中p16基因表达及其甲基化的水平,并结合临床资料进行分析。结果:胰腺癌中p16蛋白表达率为41.3%(19/46),而癌旁组织表达率为95.7%(44/46),两者有差异显著性(P<0.01)。p16蛋白阳性的19例胰腺癌标本中均未检出基因甲基化;p16蛋白缺失的27例标本中有18例检出基因甲基化,甲基化率为39.1%。p16基因甲基化与蛋白缺失有明显关系(P<0.05)。p16基因表达及其启动子区甲基化的发生率与胰腺癌的大小,患者性别﹑年龄的差异无显著意义(P>0.05),但与组织分化程度﹑淋巴结转移﹑PTNM分期有显著意义(P<0.05)。结论:p16基因启动子的异常甲基化可影响p16蛋白的表达,它们与胰腺癌的发生发展有关;p16甲基化和蛋白表达可能成为胰腺癌诊断及预后的候选标志物之一。     

p38丝裂原活化蛋白激酶信号级联在炎症反应中的作用

在急、慢性疾病中，细胞释放的炎症介质可以活化多种信号转导级联反应，丝裂原活化蛋白激酶(MAPK)信号转导通道在招募白细胞于炎症部位聚集起着重要的作用。同时，p38MAPK异构体的活化可以激活致炎细胞因子，而后刺激白细胞活化。然而，p38MAPK引起的白细胞招募这一系列的功能过程包括：粘附、游走和效应器的功能如氧化爆发以及p38MAPK介导的复杂细胞因子网络在炎症中的作用仍有待研究。针对减少炎症介质产生和以p38MAPK为治疗靶点的研究正在进行中，不远的将来可能会成为治疗炎症疾病的新策略。     

Autotransfusion after open heart surgery: the oxygen delivery capacity of shed mediastinal blood is maintained

Autotransfusion of mediastinal shed blood after open heart surgery has become a common and accepted procedure in reducing the need for homologous transfusion during the last 15 years. The objectives of the present study were to investigate the oxygen delivery capacity of autotransfused shed mediastinal blood, compared to patient-blood, during cardiopulmonary bypass and in the postoperative period.
Ten consecutive patients undergoing elective cardiac surgery were studied. Mediastinal shed blood was collected in the cardiotomy reservoir and retransfused during the first 18 postoperative hours. The oxygen delivery capacity of the blood to the tissues was calculated by use of the oxygen status algorithm (OSA 2.0) programme and measurement of the 2,3-diphosphoglycerate (2,3-DPG) concentration.
Autotransfusion volume ranged from 450–1530 ml per patient (median 824 ml). Shed blood had a mean haemoglobin level of 8.8 g/dl and 7.4 g/dl at 1 h and 6 h of autotransfusion, respectively. There were no significant changes of 2,3-DPG concentration in the patient-blood during cardiopulmonary bypass or after autotransfusion compared to preoperative values. P50 for oxygen (3.6 and 3.6 kPa) and 2,3-DPG concentrations (5.3 and 5.1 mikromol/ml erythrocyte) in shed mediastinal blood (1h and 6h postoperatively) were not significantly different compared to patient-blood.
The results demonstrate that the oxygen delivery capacity of shed mediastinal blood is maintained and that the oxygen affinity of patient-blood is not influenced by autotransfusion.     

Genomic Localization and Nucleotide Sequence of a lef-8 Gene of the Spodoptera Littoralis Nucleopolyhedrovirus

A gene similar to lef-8 of the Autographa californica (Ac) nucleopolyhedrovirus (MNPV) was identified in the Spodoptera littoralis (Spli) MNPV. The SpliMNPV lef-8-like gene was localized on the genomic map between 26.9 and 29 map units and is flanked by a chitinase gene and p47 gene. This gene arrangement differs from that of similar genes in the AcMNPV genome, where the lef-8 gene is located about 62 kbp from the chitinase gene and about 7 kbp from the p47 gene. Sequence analyses of the lef-8 gene revealed an ORF of 2730 nucleotides, predicted to encode a protein with M _r 104876. The putative protein is 60.9% identical to the AcMNPV LEF-8 and contains an identical sequence of a conserved motif of DNA-dependent RNA polymerases. Sequences downstream of the lef-8 gene contain two sequence repeats which resemble a repeated motif of the SpliMNPV enhancer element and other repetitive sequences from the viral genome. This revised version was published online in July 2006 with corrections to the Cover Date.