白细胞介素8和血管内皮细胞生长因子在肝癌组织中的表达及意义

目的 探讨白细胞介素8(1L-8)和血管内皮生长因子(VEGF)在原发性肝癌(PHC)的表达及临床病理意义.方法 采用免疫组织化学技术检测40例PHC、癌旁组织和10例正常肝组织中IL-8和VEGF蛋白的表达,RQ-PCR法检测IL-8和VFGF mRNA的表达.结果 IL-8在PHC、癌旁组织及正常肝组织中的阳性表达率分别为62.50%、82.50%和30.00%(P＜0.05),VEGF分别为67.50%、87.50%和20.00%(P＜0.01);IL-8 mRNA在PHC组织和癌旁组织表达量分别是正常肝组织的3.39和5.62倍,VEGF mRNA分别是3.78和4.64倍.IL-8 mRNA表达水平与VEGF mRNA表达水平呈正相关(P＜0.05).结论 IL-8和VEGF是一种促血管生成因子,与PHC的发生、发展及侵袭转移密切相关.     

食管癌组织血管内皮生长因子的表达与血管生成的关系

目的 探讨血管内皮生长因子(VEGF)对食管癌血管生成的影响.方法 应用SP法对90例食管鳞癌组织和34例癌旁正常黏膜进行VEGF和CD34免疫组化染色,检测VEGF表达和微血管密度(MVD),分析VEGF的表达、MVD以及食管癌临床病理特征之间的关系.结果 食管癌组织中VEGF的阳性表达率和MVD分别为71.1%和29.70±3.82,显著高于癌旁正常黏膜的11,76%和15.10±2.38(P＜0.01).VEGF表达及MVD均值与淋巴结转移、肿瘤TNM分期有关(P＜0.05和P＜0.01),与患者年龄、性别、分化程度、以及肿瘤组织学类型、肿瘤部位均无关(P＞0.05);VEGF表达与MVD均值呈显著正相关(P＜0.01).结论 VEGF异常表达在食管癌的血管生成中起重要作用,VEGF及其诱导的血管生成与食管癌的侵袭和转移密切相关.     

Maspin在原发性肝癌中的表达及其与Caspase-3、MVD的关系

目的 分析原发性肝癌(PHC)中抑癌基因maspin的表达及其与半胱天冬氨酸蛋白酶3(Caspase-3)、微血管密度(MVD)的关系.方法 采用免疫组织化学方法分别检测50例PHC组织及癌旁肝组织中maspin及Caspase-3、CD34的表达.结果 PHC组织中maspin的阳性率为28％(14/50),Caspase-3的阳性率为36％(18/50),均低于癌旁肝组织的66％(33/50)和76％(38/50),两者呈正相关(r=0.553,P＜0.01).PHC组织中的MVD为30.83±14.30,明显高于癌旁肝组织的14.47±4.00,maspin的表达与MVD呈负相关(r=-0.780,P＜0.01).结论 Maspin可能通过调节细胞凋亡蛋白酶的活性以及抑制血管生成来抑制肝细胞癌的发生发展、侵袭转移.     

ICAM-1和VEGF在原发性肝细胞癌中的表达及其临床意义

目的探讨血管内皮生长因子（Vascular endothelial growth factor，VEGF）和细胞间粘附分子-1（Intercellular adhesion molecule，ICAM-1）的表达与原发性肝细胞癌侵袭和转移的关系。方法采用免疫组织化学LSAB法对36例原发性肝癌和其癌旁组织手术切除后的石蜡标本组织中的VEGF和ICAM-1的表达及微血管密度（MVD）进行检测。结果①VEGF、ICAM-1在原发性肝癌组织中的表达明显高于癌旁组织。②在原发性肝癌中，有转移者及包膜不完整者VEGF、ICAM-1和MVD明显高于无转移者及包膜完整者。③VEGF的表达与MVD呈正相关。结论原发性肝细胞癌组织中的VEGF、ICAM-1表达与肿瘤的侵袭和转移密切相关，可作为判断转移及预后的指标     

特异性环氧化酶2与肾细胞癌血管增生的相关性研究

目的 探讨特异性环氧化酶2(COX-2)在肾细胞癌的表达及其与肾细胞癌血管增生的关系.方法 免疫组化检测肾细胞癌组织标本(85例)以及癌旁正常组织标本(48例)COX-2、血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)的表达,CD34单克隆抗体标记血管内皮细胞进行微血管密度(MVD)计数.结果 COX-2、VEGF和bFGF在癌旁正常组织中阳性表达率分别为16.7％,20.8％和22.9％,在肾细胞癌组织阳性表达率分别为77.6％、80.0％和74.1％,两组差异均有统计学意义(均P＜0.01).肾癌组织MVD为(55.47±18.47),高于癌旁正常组织的(20.42±8.72)(P＜0.01).COX-2、VEGF、bFGF表达阳性的肾细胞癌其MVD均大于表达阴性的肾细胞癌MVD(P＜0.05或P＜0.01).肾细胞癌组织COX-2表达与VEGF、bFGF表达呈显著正相关(P＜0.01).结论 COX-2在肾细胞癌组织中表达升高,与肾细胞癌血管增生密切相关.     

CD34表达与肝癌侵袭转移的关系

目的探讨CD34在人肝细胞肝癌(HCC)组织中的表达及临床意义。方法对54例HCC及相应的癌旁肝组织标本进行了CD34免疫组织化学EnVisionTM法检测;对CD34标记的阳性血管进行肿瘤微血管密度(MVD)计数,分析临床病理特征。结果 CD34呈棕黄色染色定位于血管内皮细胞膜上,在HCC组织内显示弥漫的阳性表达;而癌旁肝组织多为阴性。HCC组织MVD值(46.23±16.12),明显高于癌旁肝组织的(18.15±5.92)(P<0.01)。HCC中CD34表达与EdmonsongradeⅢ+Ⅳ、静脉浸润、肝内外转移、肝硬化有关(P<0.05)。结论 HCC中CD34异常高表达,且与部分侵袭转移指标相关。     

IL-18BP与肝脏肿瘤血管异常形成相关性的初步研究

目的 探讨IL-18BP在慢性乙型肝炎(慢乙肝)、肝炎后肝硬化(肝硬化)、原发性肝癌(肝癌)和肝血管瘤发病过程中的作用.方法 IL-18BP-N端多肽与福氏佐剂常规反复免疫新西兰白兔,制备IL-18BP抗体.应用IL-18BP抗体采用二步法免疫组化检测肝癌的癌组织及癌周组织各41例;肝硬化组织11例、慢乙肝组织9例、肝血管瘤组织4例和正常肝组织5例中的IL-18BP表达.结果 成功制备了高效价(1∶50000)的IL-18BP抗体;肝血管瘤和肝癌的癌周组织大量表达IL-18BP (100%和97.56%);两者均显著高于肝癌的癌组织、肝硬化组织和慢乙肝组织(34.15%、36.36%和22.22%)(P＜0.01);肝硬化组织中的表达也显著高于慢乙肝组织(P＜0.05);而正常肝组织表达量极少.肝血管瘤组织、癌周组织免疫组化评分值分别与癌组织、乙肝组织、肝硬化组织和正常肝组织比较均有显著统计学意义(P＜0.01).结论 IL-18BP高表达可能与肝肿瘤的局部血管异常生成相关.     

高尔基体蛋白73、AFP、VEGF在原发性肝癌组织中的表达及临床意义

目的分析评价高尔基体蛋白73（GP73）、AFP、VEGF在原发性肝癌、癌旁组织以及正常肝脏组织中的表达及临床意义。方法取原发性肝癌组织、癌旁组织及正常肝组织,分别检测GP73、AFP、VEGF的含量。结果肝癌组织中GP73、VEGF和AFP表达最强,其次为癌旁组织,正常组织中表达最弱,三者比较,差异有统计学意义（P〈0.01）。肝癌组织中,GP73和VEGF的表达均显著高于AFP（P〈0.01）。经Pearson相关分析显示GP73和VEGF在肝癌组织中的表达水平具有相关性（r=0.271,P〈0.01）。结论 GP73、VEGF和AFP在肝癌组织中呈高表达,联合检测三者有助于原发性肝癌的诊断。     

小细胞肺癌中RECK基因的表达及与VEGF和MVD的关系

目的 探讨RECK基因与血管内皮生长因子(VEGF)表达、微血管密度(MVD)在小细胞肺癌(SCLC)的表达和相关性,及其与临床病理特征的联系.方法 采用免疫组化SP法检测43例肺癌组织和10例癌旁正常肺组织中RECK和VEGF、MVD的表达水平.结果 SCLC癌组织中RECK蛋白表达低于癌旁正常组织(P值为0.003),VEGF蛋白表达和MVD值高于癌旁正常组织(P值分别为0.011和0.001).三个指标在临床病理特征分析中数据差异未见统计学意义.RECK与VEGF表达无相关,RECK与MVD呈现负相关,且当VEGF表达高时两者负相关更加显著.结论 RECK基因与SCLC的侵袭和转移可能有一定关系.RECK、VEGF、MVD与患者的临床病理特征未见明显相关性.     

生存素在肝细胞癌中的表达及其与Akt磷酸化的相关性

目的 研究抗凋亡基因生存素(survivin)在肝细胞癌中的表达及其与磷酸化蛋白激酶B(Akt)的相关性.方法 从30例肝细胞癌组织、11例癌旁组织、11例正常肝组织中提取总RNA及蛋白,利用RT-PCR、蛋白印迹,检测生存素在3种组织中的表达水平;并分析肝癌组织中生存素表达与Akt磷酸化水平的关系.结果 肝癌组织中生存素的表达水平明显高于癌旁和正常肝组织(P＜0.01);同时低分化、有肿瘤转移的肝癌其生存素表达强度明显高于高分化、无转移的肝癌(P＜0.05);相关分析表明,肝细胞癌组织中生存素的表达与Akt磷酸化的表达呈正相关(r= 0.8086,P＜0.05).结论 Akt磷酸化水平的增高可导致生存素蛋白表达水平的明显增高,生存素、磷酸化 Akt异常高表达与肝细胞癌具有密切关系,它们在肝癌的发生、发展中起着重要的作用.     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

Self-stimulation and amphetamine: Tolerance to d and l isomers and cross tolerance to cocaine and methylphenidate

The effects of the d and l isomers of amphetamine on self-stimulation responding were tested following acute and chronic administration. Tolerance and post-drug depression of responding occurred in tests with both isomers, indicating no role for p-hydroxynorephedrine (PHN) which is one of the metabolites of d-amphetamine. In the second experiment, d-amphetamine, methylphenidate and cocaine all produced quantitatively and qualitatively similar effects on self-stimulation responding following acute administration. Following chronic administration of d-amphetamine, animals showed tolerance to all three drugs, indicating cross-tolerance among them. These data are consistent with an hypothesis that tolerance and post-drug depression following chronic amphetamine treatment are the result of decreases in postsynaptic receptor sensitivity, which would lead to a decreased effectiveness of all three drugs, regardless of their pre-synaptic mechanisms.     

益生菌与肿瘤防治

益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.     

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Rationale  Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans. Objectives  The present experiments utilized a “reinforcer blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats. Materials and methods  In “nondependent” experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For “dependent” experiments, rats were made dependent in vapor/inhalation chambers. Results  Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate’s effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats. Conclusions  The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The “nondependent” paradigm may model early stages of “problem drinking” in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.     

Alprazolam and lorazepam single and multiple-dose effects on psychomotor skills and sleep

Summary The effects of alprazolam 0.5 mg and lorazepam 2 mg on cognitive and psychomotor skills were assessed in twelve normal volunteer subjects in a randomised, double-blind, crossover design. Single and multiple dose effects were monitored using a battery of tests comprising critical flicker fusion threshold (CFFT), choice reaction time (CRT), simulated car tracking, and subjective ratings of perceived sedation (LARS) and of sleep behaviour (LSEQ). Compared with placebo baseline scores, treatment with lorazepam 2 mg (both single and multiple doses) resulted in a widespread impairment of CRT, tracking accuracy, and CFFT. Single doses of alprazolam 0.5 mg reduced CFFT with respect to the placebo baseline. Single and multiple dose treatment with both drugs resulted in subjective reports of sedation, a reduction of sleep onset latency, and improved sleep quality. Only lorazepam 2 mg significantly disrupted the integrity of behaviour on waking from sleep. These results suggest important pharmacodynamic differences between the two drugs in the doses used.