Time-dependent changes in sensitivity to apomorphine and monoamine receptors following withdrawal from continuous cocaine administration in rats

The effects of withdrawal from continuous administration of cocaine on behavioral sensitivity to apomorphine and monoamine receptor density were examined in rats. Subdermal minipumps that delivered either saline or 20 mg/kg/day cocaine hydrochloride were implanted for 2 weeks. Apomorphine-induced stereotypy (0.5 mg/kg, SC) was examined in separate groups of rats either 4 hr or 7, 28, or 60 days after removal of the minipumps. Transient enhanced sensitivity to apomorphine-induced stereotypy occurred during the course of withdrawal. Animals withdrawn from cocaine for 4 hours did not differ from controls in their sensitivity to apomorphine, whereas animals withdrawn from cocaine for 7 days exhibited an increase in apomorphine-induced oral stereotypy relative to controls. However, the enhanced stereotypy response was no longer evident in animals withdrawn for 28–60 days. The animals were sacrificed after behavioral testing, and their brains were assayed for changes in monoamine receptor density in the frontal cortex, caudate-putamen, and nucleus accumbens. The density of ³H-SCH-23390-labeled D1 receptors was altered in all three regions examined in a time-dependent manner that paralleled the changes in behavioral sensitivity to apomorphine. There was a transient decrease in D1 receptor density that was evident by 7 days following withdrawal from continuous cocaine administration and was no longer evident 28 or 60 days posttreatment. There were no changes in ³H-spiroperidol-labeled D2 receptors, ¹²⁵-pindolol-labeled β-adrenergic receptors, or ³H-ketanserin-labeled 5-HT₂ receptors in any of the regions examined at both 4 hr and 7 days after termination of the cocaine infusion. These findings are discussed in terms of their relevance to developing pharmacologic treatments for withdrawal from cocaine. © 1994 Wiley-Liss, Inc.     

TBX5基因在心脏发育中的作用

近年来 ,国内外学者对控制心脏发育的相关基因做了大量的研究工作 ,其中转录因子在心脏发育中的作用成为研究热点。 TBX5转录因子在早期心脏发育 ,尤其是在心房和左心室的发育中起着关键的不可替代的作用。本文从结构特征、在心脏发育中的作用及可能的作用机制几方面对 TBX5近几年的研究进展作一综述     

Evaluating podiatry services: Testing a treatment specific measure of health status

This study reports on the preliminary testing of a new measure designed for use alongside EQ-5D in evaluating outcomes in podiatry: the Podiatry Health Questionnaire (PHQ). Individuals aged 18 years or more, receiving podiatry services in clinic or domicilliary locations across four NHS Trusts in Yorkshire and Humberside UK took part in a questionnaire survey. Respondents reported high levels of problems on all six PHQ dimensions. Correlations suggested that the PHQ and EQ-5D were measuring distinct constructs. The levels on each dimension were well defined in terms of self-rated morbidity on the PHQ visual analogue scale (PHQ_vas) and the EQ-5D_vas, although PHQ_vas appeared to be slightly more sensitive to changes in health on the dimensions. There was a strong relationship between clinicians' Podiatry Clinical Score rating and reported symptoms for four out of six PHQ dimensions and PHQ_vas. The PHQ was able to distinguish respondents in terms of their self-reported morbidity in EQ-5D and in terms of their morbidity as assessed by clinicians. It is suggested that the respondent completed PHQ appears to be a useful new measure for assessing foot-related health. However, further investigation of the psychometric properties of the measure is required.     

硒缺乏降低大鼠组织中5′-脱碘酶活性

用不同硒含量的半合成饲料(试验组饲料含硒0.005ppm,对照组饲料含硒0.105ppm),饲喂断奶的Hooded Lister大鼠6周,研究了在不同硒营养状态下,大鼠肝、肾、脑、垂体及褐脂中5′-脱碘酶活性的变化。试验进行2、4、6周后,试验组大鼠组织中GSH-Px及5′-脱碘酶活性比对照组显著降低。按组织中GSH-Px及5′-脱碘酶活性下降幅度的大小,可把各组织分别排序为:肝>肾>褐脂>垂体>脑和肝>肾>褐脂>脑>垂体。硒耗竭2、4、6周后,肝脏GSH-Px活性下降94％、99％、及99.2％,肝脏5′-脱碘酶活性下降的幅度分别为62％80％及90％。硒调节5′-脱碘酶活性可能因为硒是Ⅰ型脱碘酶的辅助因子;而Ⅱ型脱碘酶活性的变化则可能是缺硒导致组织局部T_4水平升高的间接作用。硒缺乏降低5′-脱碘酶活性会导致大鼠循环T_4水平升高,而循环T_3水平降低。     

胃癌组织中KAI1、nm23及P53的表达及其临床意义

目的:探讨正常胃黏膜、不典型增生胃黏膜及癌组织中KAI1、nm23及P53蛋白的表达．方法:应用SP法免疫组化检测22例正常胃黏膜,65例不典型增生胃黏膜及74N胃癌组织中的KAI1、nm23及P53蛋白的表达．结果:正常胃黏膜、不典型增生胃黏膜及胃癌组织中,KAI1和nm23阳性率呈降低趋势,组间差异性有统计学意义(x2=20．885, P<0．001;x2=29．133,P<0．05):P53蛋白阳性表达率呈增加趋势,组间差异性有统计学意义(x2=21．954,P<0．001)．Fisher精确概率检验显示:在胃癌组中不同的浸润深度、有无淋巴结转移和脉管侵犯组内KAI1、nm23及 P53组阳性表达率的差异性有统计学意义(x2 =20．885,P<0．001;x2=29．133,P<0．05;x2= 21．954,P<0．001);而在年龄、性别组间的差异性无统计学意义．Spearman等级相关分析显示 KAI1与nm23表达呈正相关(r=0．859,P<0．05); KAI1与P53表达呈负相关(r=-0．859,P<0．05), nm23与P53表达呈负相关(r=-0．874,P<0．05) 结论:抑癌基因KAI1与nm23的缺失以及P53 蛋白的过表达可能是胃癌发生、发展及浸润和转移的重要原因之一．     

原发性胆囊癌CD44v5、CD44v6表达及其临床病理意义的研究

目的 检测胆囊癌组织中CD44v5、CD44v6的表达,并探讨其在胆囊癌发生发展过程中的临床病理意义.方法 采用SP免疫组织化学方法,检测49例胆囊癌、10例胆囊结石伴慢性胆囊炎组织和10例正常胆囊组织中CD44v5、CD44v6蛋白表达情况.结果 CD44v5、CD44v6阳性表达率在胆囊癌组织明显高于良性组织.在胆囊癌中,CD44v5基因表达阳性率与组织学分级无关,CD4 4v6基因表达阳性率与组织学分级有关.有淋巴结转移的胆囊癌组织中,CD44v5、CD44v6阳性表达率明显高于无淋巴结转移者.结论 CD44v5、CD44v6可能在胆囊癌的淋巴结转移中起着重要的作用,CD44v5、CD4 4v6可能是了解胆囊癌病变发生发展生物学行为,淋巴结转移的重要生物学指标.     

Novel pore mutation in SCN5A manifests as a spectrum of phenotypes ranging from atrial flutter, conduction disease, and Brugada syndrome to sudden cardiac death

OBJECTIVES: The purpose of this study was to determine the clinical and biophysical characteristics of a novel SCN5A mutation. BACKGROUND: Brugada syndrome and isolated cardiac conduction defect have been linked to SCN5A mutations. METHODS: Eleven members of a western European family underwent electrophysiologic investigations and mutation analysis of the SCN5A gene. Wild-type and mutant SCN5A channels were expressed in HEK293 cells, and whole cell currents were studied using patch clamp procedures. RESULTS: A novel mutation, R376H, in the first pore segment of SCN5A variably causes Brugada syndrome and/or conduction disease in a single family. Biophysical analysis demonstrated a significant current reduction for the mutant, a pathophysiologic profile consistent with Brugada syndrome and isolated cardiac conduction defect. Among 11 family members, 9 were carriers of the mutation. The proband's initial presentation was a saddleback Brugada ECG, atrial flutter, and diffuse conduction disturbances. He had no inducible ventricular arrhythmias but experienced sudden cardiac death. His brother was affected by atrial flutter and had a clear conduction disorder, but he did not display baseline or evocable ECG signs of Brugada syndrome. He received an implantable cardioverter-defibrillator that delivered one appropriate shock after 1 year of follow-up. The phenotype in the family members was highly variable and ranged from noninducible and inducible asymptomatic carriers of the mutations to isolated conduction disease and to symptomatic Brugada syndrome. CONCLUSIONS: We describe the functional characterization of a novel SCN5A pore mutation, R376H, with variable clinical expression in the same family. Differentiating between electrophysiologic entities (Brugada syndrome-isolated cardiac conduction defect) is more challenging. Recognition of factors modifying the clinical presentation may be important for clinical decision making.     

聚对苯撑乙炔的合成及光谱性能-共轭主链被间位苯环阻隔

报道了一种阻隔型聚对幕撑乙炔((PPE)的合成与电致发光特性，合成的模型小分子证明，在聚对苯撑乙炔(PPV)主链引入间位幕环，可阻隔PPV的有效共轭长度，改变其发光颜色，研究了电致发光暑件ITO／m-PPE／Al的电致发光特性。     

微泵输注氟尿嘧啶结合生长抑素治疗壶腹部周围癌

目的 :生长抑素 (SS)结合氟尿嘧啶 (5 - Fu)治疗晚期壶腹部周围癌的疗效评价。方法 :2 8例晚期壶腹部周围癌患者均采用静脉插管及随身携带微型输注泵 ,SS/ 5 - Fu持续静脉滴注 (civ法 )。结果 :经 2周期治疗后 ,临床症状缓解 (DRSI)为 89.3% (2 5 / 2 8) ;肿瘤完全缓解 (CR)占 3.7% ,部分缓解 (PR) ,占 2 8.6 % ,稳定 (NC)占 4 6 .4 % ,有效率为 32 .1%。结论 :SS/ 5 - Fu化学治疗效果稳定 ,毒副作用轻微 ,是治疗晚期壶腹部周围癌的有效手段之一。