p21-ras、p53和VEGF在甲状腺乳头状癌中的表达及意义

目的　研究原癌基因Ras、抑癌基因p5 3及血管内皮生长因子 (VEGF)在甲状腺乳头状癌中的表达及相关性。方法　应用免疫组织化学S P法对 4 0例甲状腺乳头状癌中p2 1 ras、p5 3及VEGF的表达进行研究。结果　甲状腺乳头状癌中存在p2 1 ras、p5 3及VEGF的过度表达 ;VEGF的表达与p2 1 ras、p5 3的表达显著相关 (P <0 .0 5 ) ;VEGF的表达与甲状腺乳头状癌淋巴结转移显著相关 (P <0 .0 5 )。结论　p2 1 ras、p5 3、VEGF在甲状腺乳头状癌的发生发展过程中起重要作用 ;VEGF的表达与p2 1 ras、p5 3表达显著相关 ,可能受其调控。     

栀子标准汤剂量值传递规律研究

目的 研究栀子饮片到标准汤剂的量值传递规律。方法 收集23批栀子饮片,制备标准汤剂,测定出膏率,建立饮片和标准汤剂的HPLC指纹图谱,采用三重四级杆飞行时间质谱（triple quadrupole time-of-flight mass spectrometry,Triple-Q-TOF/MS）技术对标定的共有峰进行成分鉴定,对采用对照品比对确认的成分进行含量测定,以出膏率、指纹图谱共有峰传递数及峰面积比值变化、成分转移率为指标,分析栀子饮片到标准汤剂的量值传递规律。结果 栀子饮片指纹图谱标定共有峰26个,其中25个传递到了标准汤剂,共有峰个数传递率96.15%,26个共有峰的成分均得到鉴定,其中7个环烯醚萜类成分栀子苷、京尼平龙胆双糖苷、羟异栀子苷、山栀苷、京尼平苷酸、去乙酰车叶草酸甲酯（DAAME）、鸡矢藤次苷甲酯（SME）,2个西红花苷类成分西红花苷I、Ⅱ,2个黄酮类成分芦丁和异槲皮苷,1个单环单萜类成分jasminoside B,1个有机酸类成分绿原酸共计13个成分采用照品比对确认,标准汤剂和饮片共有峰面积比值与成分转移率呈现较好的正向直线关系,7个环烯醚萜类成分合计平均转移率70.90%,其中主要成分栀子苷平均转移率77.16%,西红花苷I、Ⅱ、芦丁、异槲皮苷、jasminoside B、绿原酸平均转移率分别为47.09%、39.56%、63.25%、51.95%、61.42%、75.70%,标准汤剂平均出膏率为28.91%。结论 阐明了栀子标准汤剂量值传递规律,为栀子配方颗粒及含栀子经典名方制剂研究奠定了基础。     

Astrocytes in the damaged brain: Molecular and cellular insights into their reactive response and healing potential

Long considered merely a trophic and mechanical support to neurons, astrocytes have progressively taken the center stage as their ability to react to acute and chronic neurodegenerative situations became increasingly clear. Reactive astrogliosis starts when trigger molecules produced at the injury site drive astrocytes to leave their quiescent state and become activated. Distinctive morphological and biochemical features characterize this process (cell hypertrophy, upregulation of intermediate filaments, and increased cell proliferation). Moreover, reactive astrocytes migrate towards the injured area to constitute the glial scar, and release factors mediating the tissue inflammatory response and remodeling after lesion. A novel view of astrogliosis derives from the finding that subsets of reactive astrocytes can recapitulate stem cell/progenitor features after damage, fostering the concept of astroglia as a promising target for reparative therapies. But which biochemical/signaling pathways modulate astrogliosis with respect to both the time after injury and the type of damage? Are reactive astrocytes overall beneficial or detrimental for neuroprotection and tissue regeneration? This debate has been animating this research field for several years now, and an integrated view on the results obtained and the possible future perspectives is needed. With this Commentary article we have attempted to answer the above-mentioned questions by reviewing the current knowledge on the molecular mechanisms controlling and sustaining the reaction of astroglia to injury and its stem cell-like properties. Moreover, the cellular/molecular mechanisms supporting the detrimental or beneficial features of astrogliosis have been scrutinized to gain insights on possible pharmacological approaches to enhance astrocyte neuroprotective activities.     

Impact of Critical Illness Polyneuromyopathy in Rehabilitation: A Prospective Observational Study

Background

Critical illness polyneuromyopathy (CIPNM) increasingly is recognized as a source of disability in patients requiring intensive care unit (ICU) admission. The prevalence and impact of CIPNM on patients in the rehabilitation setting has not been established.

联合检测胎儿血红蛋白、α1微球蛋白、sFlt-1及PIGF对子痫前期的诊断价值

目的探查孕妇外周血清胎儿血红蛋白（HBF）、α1-微球蛋白（A1M）、可溶性血管内皮生长因子受体-1（snt-1）、胎盘生长因子（P1GF）以及尿液中α1-微球蛋白（u—A1M）在正常妊娠组和子痫前期（PE）组的表达差异,探讨其在子痫前期发病机制中的作用。方法采用酶联免疫吸附法（ELISA）检测23例正常妊娠孕妇、50例子痫前期孕妇（N轻度=20例、N重度=30例）外周血清中HBF、A1M、sFlt-1、P1GF以及尿液A1M水平,计算sFlt—1／P1GF比值,应用logistic回归和接受者工作特征曲线（ROC曲线）评价指标单独及联合应用对子痫前期的诊断价值。结果子痫前期组血清HBF、AIM、sFlt-1、sFlt-1／P1GF比值以及尿液A1M水平均高于正常妊娠组（P〈0．05）,子痫前期组PlGF水平低于正常妊娠组（P〈0．05）。血清HBF、A1M、sFlt-1、P1GF、sFlt-1／P1GF比值以及尿液A1M的ROC曲线下面积（AUC）依次为：0．794,0．805,0．690,0．754,0．801,0．648。指标联合后AUC增大,敏感度和特异度更佳。结论HBF、A1M、sFlt—1、P1GF可能参与了子痈前期的发病机制,联合检测可以提高子痫前期的诊断价值。     

内瘤变创口愈合的影响

目的研究医用生物蛋白胶对子宫颈电热圈环切术（100pelectrosurgicalexcisionprocedure，LEEP）治疗宫颈上皮内瘤变，术后创口愈合的影响。方法选择符合诊断和手术条件的宫颈上皮内瘤变患者128例，分治疗组82例和对照组46例，均用LEEP治疗，术后创口分别敷用医用生物蛋白胶和无菌纱布，观察两组并发症（创面感染、肉芽生长、脱痂期出、宫颈管狭窄）发生率，阴道持续出血时间和出血量及创面愈合时间，术后2年疗效及复发率，并进行统计分析。结果两组的并发症发生率分别为2．44％和15．22％，阴道出血持续时间≤2周、〉2周而≤3周、〉3周而≤5周、≥5周的发生率分别为78．05％、23．91％、19．51％、50．00％和2．44％、17．39％、0．00％、8．70％，阴道出血量≤20ml、21～49ml、≥50ml的发生率分别为78．05％、34．78％、21．95％和52．17％、0．00％、13．04％，创面愈合平均时间分别为12．1±5．3天和18．4±4．8天，术后2年随访有效率分别为98．78％和86．96％，两组间比较均有显著差异（P〈0．05）。结论医用生物蛋白胶可促进LEEP治疗宫颈上皮内瘤变创口的愈合，减少并发症，提高治愈率。     

Efficacy of biperiden and atropine as anticonvulsant treatment for organophosphorus nerve agent intoxication

The ability of the nerve agents tabun, sarin, soman, GF, VR, and VX to produce brain seizures and the effectiveness of the anticholinergics biperiden HCl or atropine SO₄ as an anticonvulsant treatment were studied in a guinea-pig model. All animals were implanted a week prior to the experiment with cortical electrodes for electroencephalogram (EEG) recordings. On the day of exposure, the animals were pretreated with pyridostigmine (0.026 mg/kg, i.m.) 30 min prior to challenge with a 2 × LD₅₀ dose (s.c.) of a given agent. In separate experiments, animals were challenged with 5 × LD₅₀ (sc) of soman. One minute after agent challenge, the animals were treated intramuscularly (i.m.) with 2 mg/kg atropine SO₄ admixed with 25 mg/kg 2-PAM Cl and then observed for the onset of seizure activity. Five minutes after the start of nerve agent-induced EEG seizures, animals were treated i.m. with different doses of biperiden HCl or atropine SO₄ and observed for seizure termination. The anticonvulsant ED₅₀ of biperiden HCl and atropine SO₄ for termination of seizures induced by each nerve agent was calculated and compared. With equally toxic doses (2 × LD₅₀) of these agents, continuous EEG seizures (status epilepticus) developed in all animals challenged with soman, tabun, or VR, and in more than 90% of the animals challenged with GF or sarin. In contrast, only 50% of the animals developed seizures when challenged with VX. The times to onset of seizures for soman, tabun, GF, and sarin were very similar (5–8 min) while for VR, it was about 10 min. In the case of VX, not only was the time to seizure development longer (20.7 min), but the seizure activity in 19% of the animals terminated spontaneously within 5 min after onset and did not return. Under these conditions, the anticonvulsant ED₅₀s of biperiden HCl for soman, GF, VR, tabun, sarin, and VX were 0.57, 0.51, 0.41, 0.2, 0.1, and 0.09 mg/kg, respectively, while those of atropine SO₄ for soman, VR, tabun, GF, sarin, and VX were 12.2, 11.9, 10.4, 10.3, 5.1, and 4.1 mg/kg, respectively. In separate experiments, the anticonvulsant ED₅₀ doses of biperiden for animals challenged with 2 or 5 × LD₅₀ of soman were 0.48 (95% confidence limits 0.25–0.73) or 0.57 (95% CI 0.38–0.84) mg/kg, respectively, while the anticonvulsant ED₅₀s for atropine (12.2 mg/kg, i.m.) were identical under these same two challenge conditions. The present study demonstrates that all nerve agents can produce status epilepticus and that the therapeutic effectiveness of atropine and biperiden roughly paralleled the seizurogenic potential of these agents. Received: 16 November 1999 / Accepted: 9 February 2000     

Transport Characteristics of Fexofenadine in the Caco-2 Cell Model

PURPOSE: To investigate the membrane transport mechanisms of fexofenadine in the Caco-2 model. METHODS: Transport studies were performed in Caco-2 cell monolayers 21-25 days after seeding. The apparent permeability (Papp) of fexofenadine was determined in the concentration range 10-1000 microM in the basolateral-to-apical (b-a) and 50-1000 microM in the apical-to-basolateral (a-b) direction. The concentration-dependent effects of various inhibitors of P-glycoprotein (P-gp) (GF120918, ketoconazole, verapamil, erythromycin), multidrug resistant associated protein (MRP) (indomethacin, probenecid), and organic anion transporting polypeptide (OATP) (rifamycin SV) on the bidirectional transport of 150 microM fexofenadine were also examined. RESULTS: Fexofenadine displayed polarized transport, with the Pappb-a being 28- to 85-fold higher than the Papp(a-b). The Papp(a-b) was independent of the concentration applied, whereas Pappb-a decreased with increasing concentration (Vmax = 5.21 nmol cm(-2)s(-1) and K(M) = 150 microM), suggesting saturation of an apical efflux transporter. All four P-gp inhibitors had a strong, concentration-dependent effect on the Papp of fexofenadine in both directions, with GF 120918 being the most specific among them. The IC50 of verapamil was 8.44 microM on the P-gp-mediated secretion of fexofenadine. The inhibitors of OATP or MRP appeared not to affect the Papp(a-b) of fexofenadine in the Caco-2 model. CONCLUSIONS: This study clearly indicates that P-gp was the main transport protein of fexofenadine in the Caco-2 model. Even though P-gp was completely inhibited, fexofenadine was predicted to have a low fraction dose absorbed in humans due to poor intestinal permeability, and low passive diffusion seems to be the major absorption mechanism.