CIK治疗恶性肿瘤的研究进展及临床应用现状

用免疫活性细胞输注的过继免疫是肿瘤生物治疗的研究热点之一。此疗法不仅是常规抗肿瘤治疗的补充,更是为晚期不宜手术或无法承受放疗化疗所带来的副作用的患者开辟了一个新的治疗途径,成为人类抗击肿瘤最有希望的战略措施之一。CIK(Cytokine Induced Killer)是继LAK,TIL及CD3AK细胞之后,具有细胞增殖倍数高、肿瘤杀伤能力强等特点的新一代过继免疫抗肿瘤细胞。本文就CIK的特点,抗肿瘤机制,及临床应用现状等作一综述。     

Identification of molecular mechanism for actions of existing medicines and its application for drug development

As a new strategy for drug discovery and development, we propose here the establishment of drug re-profiling strategy. In this strategy, the actions of existing medicines, whose safety and pharmacokinetic effects in humans have been confirmed already, are examined comprehensively at the molecular level and the results are used for the development of new medicines. For example, identification of the mechanisms underlying the side effects of medicines enables us to develop safer drugs. The results can also be used for developing existing drugs for use as medicines in treatment of other diseases. Promoting this research strategy could provide breakthroughs in drug discovery and development by pharmaceutical companies.     

紫檀芪延缓糖尿病肾病发展的作用及机制

目的研究紫檀芪对链脲佐菌素(STZ)诱导的糖尿病肾病(DN)进展的延缓作用及可能机制。方法将C57BL/6J小鼠(n=50)随机分为对照组、模型组、低剂量药物组(20 mg·kg^-1)、中剂量药物组(40 mg·kg^-1)和高剂量药物组(80 mg·kg^-1),每组10只。对照组和模型组灌胃5 g·L^-1羧甲基纤维素钠,高、中、低剂量药物组小鼠灌胃相应剂量的紫檀芪12周。测定24 h蛋白尿,检测血液中血糖、血肌酐和血尿素氮水平,检测肾脏组织中炎症因子白介素-6(IL-6)和单核细胞趋化蛋白-1(MCP-1)的表达,HE染色和PAS染色检测肾脏组织的病理改变情况,Western blot法测定肾脏组织中沉默信息调节因子1(SIRT1)蛋白的表达。结果紫檀芪可延缓STZ诱导的1型DN的进展,降低血肌酐和血尿素氮的水平。紫檀芪对血糖及24 h尿蛋白无影响。紫檀芪可降低肾脏组织中炎症因子IL-6和MCP-1的表达。HE染色和PAS染色发现,紫檀芪能降低糖尿病小鼠肾小球体积和基底膜厚度,还能增加糖尿病小鼠肾脏组织中SIRT1蛋白的表达。结论紫檀芪可延缓1型DN的发展,其机制与其调节SIRT1的表达有关。     

医院制剂皮肤刺激性的试验

目的：考查18种医院外用非标准制剂对皮肤的刺激性,进行医院制剂芗的安全性评价,为合理用药提供资料。方法：制剂在短期接触家兔皮肤后,在规定的时间内研究其对家兔皮肤所产生的刺激反应及其他不良反应。结果：中度刺激的受试药2种,轻度刺激的8种,无刺激反应的8种。结论：提示临床应用对皮肤有中度刺激,且刺激分值较高者,应改善制剂以减轻不良反应;对破损皮肤有刺激反应者,应尽量避免或慎用于患者的皮肤破损处。     

Midkine在肿瘤发生发展中的作用和作为生物标志物的应用

中期因子（MK）是一种新的肝素结合生长因子,因起初在孕中期小鼠胚胎肾脏发现其大量表达而得名。 MK在多种恶性肿瘤组织中高表达,且在肿瘤的发生、发展及转移中发挥着重要作用,可促进肿瘤细胞增殖、迁移和 肿瘤血管生成等过程,并影响肿瘤患者的预后,而在正常组织或癌旁组织中低表达甚至不可测。值得注意的是,MK 是一种可溶性细胞因子,在血液和其他体液,如尿液和脑脊液中升高非常明显,这使得其成为一种相对方便、可获 得、非侵入性和廉价的生物标志物,可用于人群筛查和早期疾病检测。目前MK已被证明是一种能够显著提高癌症 检测、管理和治疗水平的生物标志物。本文就MK与肿瘤发生发展、预后及在生物标志物中的应用的研究现状进行 综述。     

血管紧张肽Ⅱ受体拮抗剂氯沙坦钾的临床应用及其发展现状

氯沙坦钾属于非肽类血管紧张肽Ⅱ的Ⅰ型受体(AT1)拮抗剂,临床用于治疗高血压。文章阐明了氯沙坦钾的临床应用,而且与ACE抑制剂相比,氯沙坦钾不抑制缓激肽降解,不引起咳嗽和血管性水肿,治疗高血压的疗效与目前各一线降压药物相同,并具有耐受性好、不良反应低的优点。近年此类药物的发展较快,逐渐成为临床治疗高血压的一线药物。     

前列地尔脂质体的制备及刺激性考察

目的 :制备前列地尔脂质体以减少其静脉注射的刺激性。方法 :采用逆相蒸发法制备前列地尔脂质体 ,用超滤膜测定脂质体的包封率及其释放、马尔文粒径仪测定平均粒径 ;并通过动物实验比较静脉注射的刺激性。结果 :前列地尔脂质体的包封率可达到 94 % ,超声后和高压匀质后的粒径为(732±s 35 )nm和 (6 7± 7)nm ,刺激性得到显著改善。结论 :前列地尔脂质体可以显著降低静脉注射引起的刺激性。     

Review on skin and mucous-membrane irritation tests and their application

The history and present state of routine testing for skin and eye irritation are reviewed. Various changes to the traditional Draize test have been proposed by a number of workers, and it is concluded that the adoption of the modified Draize test should be the first decisive step to be taken in the search for new methods in irritation testing. Other new methods, such as testing using organ and cell cultures, and determination of the relationship between physico-chemical properties and irritative potential, have been reported. Although at present these techniques require further validation, some of them show considerable promise of reliably predicting the irritative effects of substances on humans.     

Quantitative component analysis of mixtures for risk assessment: application to eye irritation

A methodology called quantitative component analysis of mixtures (QCAM) was used to analyze an existing set of product formulation data to determine if the irritating ingredients in the mixtures could be identified. Eye irritation scores, based on a rat model, for 18 mixtures having a composite total of 37 components, were analyzed by QCAM. QCAM relates a net toxicity measure of a mixture to the toxicities of the individual components of the mixture through linear, quadratic, and pairwise cross-component concentration-dependent interactions. A correlation model is established using a particular genetic algorithm employing either multidimensional linear regression or partial least-squares regression fitting. Cornea eye irritation and average eye irritation are well-explained in terms of a linear model of, at most, three components over the set of mixtures. Moreover, extensive cornea and average eye irritations are due to only one of these three components of the mixtures. Also, one of the three significant components was predicted to decrease the extent of eye irritation, and subsequently identified as an "anti-irritant" in contact lens solutions. A reasonable linear correlation model could also be developed for conjunctiva irritation, but no significant iris irritation model could be constructed. The addition of quadratic and/or cross-component concentration terms to a linear correlation model did not statistically improve the overall resultant model. The QCAM models permit estimation of the intrinsic (self) toxicity of each of the components of a mixture, and may aid in the reduction, and ultimate elimination, of the need for animal eye irritation studies.     

The vulva is relatively insensitive to menses-induced irritation

Skin patch testing of menses and venous blood on the vulva (labia majora) and the upper arm was performed to assess the potential contribution of these biological fluids to vulvar irritation during menstruation. After 24 and 48 hours of occlusive exposure, the skin of the labia majora was relatively unaffected by these fluids compared to the skin of the upper arm: no significant irritation was observed on the labia at either exposure time, but discernible irritation was elicited on the upper arm after 48 hours of exposure. Pre-treatment of the upper arm with a petrolatum-based emollient attenuated the upper arm response. Semi-occlusive conditions also reduced the degree of upper-arm irritation elicited test materials and an irritant control, sodium lauryl sulfate. The relative insensitivity of the vulva to irritation by menses or blood was not predictable a priori because some irritants elicit heightened responses on the vulva relative to the arm (3). These results suggest that the vulva (labia majora) may be adapted to be less sensitive to menses-induced skin irritation than other anatomical sites.     

Further studies of the mechanism of counter irritation by turpentine

Summary The influence of counter irritation by turpentine (0.2 ml) on zymosan-and carrageenan-oedemas was investigated in the rat. Zymosan-oedema was inhibited by mepyramine and methysergide and by leucopenia. It was not modified by captopril and developed normally in kininogendeficient Brown Norway rats. Leucocytes and mast cell amines but not kinins are thus involved in zymosan-oedema. The last phase of this reaction was inhibited by counter irritation alone, but the odema was largely depressed by counter irritation in rats pretreated with mepyramine and methysergide.Carrageenan-oedema was increased by kininase inhibitors and inhibited by leucopenia in normal rats. This inflammatory reaction had a small developement and was not increased by kininase inhibitors in kininogen-deficient BN rats. Leucocytes and kinins participate in the developement of this inflammatory reaction in normal rats while kinins are lacking in deficient rats. Counter irritation depressed carrageenan-oedema in deficient Brown Norway rats and suppressed the potentiating effect of kininase inhibitors in normal rats. Carrageenan oedema was nearly abolished in turpentine-treated leucopenic rats.These results suggest that the anti-inflammatory effect of counter irritation by turpentine could depend on a reduction of leucocyte accumulation into zymosan-oedema and on a reduction of both kinin formation and of leucocyte accumulation into carrageenan-oedema. The significance of T-kininogen as acute phase reactant is discussed.     

咪达普利、缬沙坦抑制动脉粥样硬化的作用及机制

目的研究咪达普利，缬沙坦抑制动脉粥样硬化的作用及其机制。方法40只纯种大白兔随机分为4组。喂养8周后测定各组血清中总胴固醇（TC）、甘油三酯（TG）及低密度脂蛋白胆固醇（LDL），免疫组化观察粥样硬化斑块中STAT3、P21、CDK4的表达情况。结果高脂组、药物干预组血清TC、TG、LDL—C水平较对照组显著升高。STAT3、CDK4在药物干预组中表达较高脂组明显减少．而P21在药物干预组的表达较高脂组则明显升高。结论咪达普利、缬沙坦可明显抑制动脉粥样硬化的发生，其机制可能与抑制STAT3的信号传导和平滑肌增值有关。     

依达拉奉清除自由基机制及临床应用

研究证实,多种人类疾病的发生与机体过量自由基的产生相关,过量自由基损伤脂质,蛋白质和DNA等生物大分子,导致对机体的有害作用。依达拉奉(edaravone)为强效自由基清除剂,于2001年在日本上市,临床上主要用于治疗急性缺血性脑中风。本文对依达拉奉清除自由基的机制和治疗多种人类疾病的研究进展作简要概述,主要介绍了依达拉奉在治疗脑、心脏等多器官的缺血/再灌注损伤,肌萎缩侧索硬化症(ALS)、帕金森病(PD)、阿尔茨海默病(AD)、多发性硬化症等神经性疾病,癫痫,动脉粥样硬化,肝、肺纤维化病变,类风湿性关节炎和突发性耳聋等多种人类疾病中的应用,为进一步开发依达拉奉在临床上的新用途提供参考。     

蓖麻毒素的毒性作用机制及其在肿瘤治疗中的应用

蓖麻毒素对哺乳动物细胞具有很强的毒性,属于Ⅱ型核糖体失活蛋白。其A链是活性链,可使核糖体失活,从而使蛋白质合成受阻,细胞死亡。基于蓖麻毒素的细胞毒性,人们将蓖麻毒素及其A链应用于肿瘤治疗领域,目的在于特异性杀伤肿瘤细胞,并减小对正常细胞的毒性。本文就蓖麻毒素的分子结构、毒性机制以及近年来在肿瘤治疗领域的研究进展作一综述。     

利拉鲁肽的临床应用及其作用机制的研究进展

胰高血糖素样肽-1(GLP-1)是小肠消化食物时L细胞分泌的一种促胰岛素激素,可以促进胰岛素分泌,从而维持葡萄糖稳态,其受体广泛分布于胰岛、心脏、肺、皮肤等器官中.利拉鲁肽是一种长效的GLP-1类似物,目前被广泛用于治疗2型糖尿病.近年来研究发现,利拉鲁肽在肥胖症、神经系统疾病、心血管系统疾病中均发挥有益作用.对利拉鲁...     

指数富集的配体系统进化技术的发展及其在临床治疗中的应用

基于作为配基的寡核苷酸的三维立体结构,指数富集的配体系统进化（SELEX）技术能够筛选获得高效、特异结合靶分子的寡核苷酸适体。该配基由于其亲和力高、特异性强、免疫原性低、筛选周期短及适用范围广等特性,在临床诊断和疾病治疗中拥有多项优势,具有被研制成新型适体药物应用于临床的巨大潜力。本文从SELEX技术的发展、配基的修饰改造、临床治疗的优势、配基作为靶蛋白功能阻断剂和药物分子靶向载体进行的临床应用等几个方面,对寡核苷酸适体在临床疾病治疗中的应用进行综述。     

硝酸咪康唑乳浊液和环包物的药效及刺激性比较

目的:比较硝酸咪康唑乳浊液和环包物的药效和刺激性.方法:运用试管稀释法进行体外抗真菌试验,阴道内接种白色念珠菌进行体内抗真菌试验; 制备宫颈炎模型,观察硝酸咪康唑乳浊液和环包物对黏膜的刺激性.结果:体外抗真菌试验的结果显示乳浊液的抑菌浓度小于环包物;体内抗真菌试验显示用药组白色念珠菌数与对照组相比均明显减少,但环包物组的抑菌效果略差于乳浊液组(P> 0.05 );刺激性试验显示环包物组显著小于乳浊液组.结论:硝酸咪康唑乳浊液的抑菌作用较强,而环包物的刺激性较小.     

A modified HET-CAM assay approach to the assessment of anti-irritant properties of plant extracts.

Hen's egg--chorioallantoic membranes were used to screen for and assess anti-irritant properties among aqueous extracts of plants (HET-CAM tests), in connection with searches for plant-derived substances with topical anti-irritant action. The main question to be answered was whether CAM-assay screening of plant extracts could provide a useful route to identifying promising anti-irritant extracts for follow-up clinical testing. To be useful, the method would have to flag materials with strong anti-irritant properties, and would have to avoid registering false negatives. The tests conducted provided positive indications. We measured the delays in onset of three manifestations of membrane irritation-vascular hemorrhaging, membrane lysis and membrane coagulation-observed with test substances relative to positive controls. Aqueous 15% lactic acid, a commonly used irritant in direct tests on human skin, was employed as the test irritant in this study. The ratio [irritation onset times after test substance pre-treatment]:[onset times without test substance pretreatment] was used to measure the anti-irritant power of test substances. A scoring notation was devised for this which treats the delay parameters as independent effects. Most tested plant extracts showed no significant irritant or anti-irritant effects. Among the apparently anti-irritant plant extracts (approx. 10% of all those tested), most showed their greatest effect against hemorrhaging. Lesser but still readily measurable effects against membrane lysis and coagulation were also observed in nearly all the apparently anti-irritant extracts. Two of the tested extracts proved to be membrane irritants. Some key CAM assay results were compared with results obtained in direct tests on human skin using the same test irritant (15% lactic acid). In these comparative tests on skin, an essentially similar pattern of efficacy was obtained, with the plant extract deemed best in the CAM screenings, outperforming the benchmark anti-irritant hydrocortisone. From these initial results it appears that physiological CAM assays may prove useful in screening natural materials for anti-irritant properties, as alternatives to mechanism-dependent biochemical assays, or expensive direct screening tests on human subjects. Further work remains to extend the CAM screening approach to irritants other than lactic acid, and to assess its quantitative powers of prediction of topical anti-irritancy.