肝细胞癌组织中 IL-18BPc 和 VEGF 的表达及与肿瘤血管形成的关系

目的 探讨IL-18BPc和VEGF在原发性肝细胞癌组织中的表达及其与肿瘤血管形成之间的关系。方法 应用免疫组织化学SP法检测IL-18BPc和VEGF在34例肝细胞癌组织、34例癌旁肝组织及12例正常肝组织的表达,通过CD34免疫组织化学染色评价肿瘤组织MVD值,分析IL-18BPc表达与VEGF表达及MVD的关系。结果 IL-18BPc在肝癌组织中的表达阳性率高于癌旁肝组织(P＜0.01)及正常肝组织(P＜0.01),且肝癌出现侵袭转移者较未出现侵袭转移者其IL-18BPc表达阳性率高(P＜0.01);VEGF在肝癌组织中的表达高于癌旁肝组织(P＜0.01)及正常肝组织(P＜0.01);IL-18BPc和VEGF在肝细胞癌中表达呈正相关(r=0.357, P=0.037);肝癌组织MVD值与高于癌旁肝组织(P＜0.01)及正常肝组织(P＜0.01);肝癌组织中, IL-18BPc阳性表达者MVD值高于阴性表达者(P=0.004)。结论 IL-18BPc可能通过上调VEGF的表达促进肝细胞癌血管形成。     

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.     

HIF-1α在不同肝脏组织中的表达状态研究

目的研究乏氧诱导因子-1α在原发性肝细胞癌组织、癌旁肝硬化组织、非癌肝硬化组织及正常肝组织中的表达状态。方法收集2009年3月～2010年9月在笔者所在医院诊断原发性肝细胞癌而行手术治疗的56例肝癌组织标本,同时收集合并有肝硬化背景的癌旁肝组织27例,因乙肝肝硬化门脉高压症而行门奇断流术的非癌肝硬化组织23例及11例取自肝血管瘤周围或肝外伤后切除的肝组织作为对照。通过免疫组织化学技术SP染色方法检测HIF-lα在4种肝脏组织中的蛋白表达情况。结果在肝细胞癌组织中HIF-lα蛋白的阳性表达率为71.4%,明显强于癌旁肝硬化组织中(48.1%)的表达,两者比较,差异有统计学意义(P<0.05);癌旁肝硬化组织中的阳性表达率又强于非癌肝硬化组织中的表达(17.4%),两者比较,差异有统计学意义(P<0.05);但非癌肝硬化组织与正常肝组织(9.1%)比较,HIF-lα的表达则差异无统计学意义(P>0.05)。结论 HCC中存在着乏氧现象,并以其为始动因素诱导了调控因子HIF-lα基因的过度表达。     

Ezrin在小鼠肝癌组织中的表达及临床研究

目的 探讨细胞骨架连接蛋白Ezrin在肝癌组织、肝硬化、正常肝组织中的表达及其与肿瘤转移的关系.方法 选择昆明雄性小鼠75只,体重18～22 g.随机分为3组,正常对照组15只,肝硬化组25只,用10%四氯化碳橄榄油灌胃,每只灌服0.2 ml,每周4次,共16周,直至病理显示假小叶形成.肝癌组35只,从传代昆明雄性小鼠腹腔抽取癌性腹水5 ml,离心,应用下层较浓稠呈稀糊样的半液态物,调整肝癌细胞的浓度为106个/ml,将H22肝癌细胞株沿肝脏长轴与水平面成30°角注入0.02 ml,于术后第7、14、20天开腹观察肝脏肿瘤并取肿瘤组织,用免疫组化方法检测小鼠肝脏组织中Ezrin的表达情况.结果 移植性肝癌组织中Ezrin的阳性表达率显著强于正常肝组织和肝硬化组织,3组织中Ezrin的强阳性表达率差异均有统计学意义(P＜0.01),造模第20天小鼠肝癌Ezrin强阳性表达明显强于造模第7、14天小鼠肝癌Ezrin强阳性表达,差异有统计学意义(P＜0.01).3组AFP水平检测差异无统计学意义(P＞0.05).结论 Ezrin的高表达与肝癌细胞的恶性演进有关.     

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.     

乙肝及原发性肝癌患者中抗核抗体的检测

目的 探讨慢性乙型肝炎(简称乙肝)及原发性肝癌患者血液中抗核抗体的表达特点及临床意义。方法 采用金标免疫斑点法对526份血液标本进行抗核抗体(ANA)检测，其中乙型肝炎组295例、乙肝后肝硬化组80例、乙肝后原发性肝癌31例及对照组120例。结果对照组ANA阳性者2．50％(3例)；与对照组比，乙型肝炎组ANA阳性为10．51％(31例)，P＜0．01，肝硬化组ANA阳性37．50％(30例)，P＜0．01，原发性肝癌组ANA阳性29．03％(9例)，P＜0．01，均有显著差异；肝硬化组与乙肝组对比，P＜0．01，原发性肝癌组与乙肝组对比，P＜0．01；肝硬化组与原发性肝癌组之间差异无显著性，P＞0．05。结论 乙肝患者抗核抗体阳性率明显增高，肝硬化组与原发性肝癌组抗核抗体的阳性牢更高，抗核抗体阳性时可能提示着预后不良，抗核抗体在慢性乙型肝炎的发展和转归中有一定意义。     

Hiwi基因在肝癌组织中的表达

目的 研究Hiwi基因mRNA及Hiwi蛋白在肝癌组织中的表达.方法 92例肝癌及癌旁组织标本,应用RT-PCR、Western blot及免疫组化方法分别检测肝癌和癌旁组织中Hiwi基因mRNA及蛋白的表达.结果 肝癌组织Hiwi基因mRNA和Hiwi蛋白表达量显著高于癌旁组织(P＜0.05).Hiwi蛋白主要在肿瘤和癌旁组织细胞胞浆中呈阳性表达.肝癌组织中Hiwi阳性表达率为65.2%(60/92),显著高于癌旁组织的27.2%(25/92)(P＜0.05).结论 Hiwi基因mRNA及蛋白在肝癌组织中均呈高表达,可能在肝癌的发生、发展过程中起重要作用.     

原发性肝癌患者血清IL-18、VEGF和sVCAM-1水平变化及临床意义

目的 研究原发性肝癌( PHC)患者血清白细胞介素-18 (IL-18)、血管内皮生长因子(VEGF)与可溶性血管细胞粘附分子-1 (sVCAM-1)水平及临床意义.方法 采用双抗体夹心酶联免疫吸附法( ELISA)检测15例原发性肝癌患者治疗前后血清IL-18、VEGF、sVCAM-1水平,并与正常对照组比较.结果 PHC患者治疗前血清IL-18、VEGF、sVCAM-1较正常对照组明显升高(P均＜ 0.05); PHC患者治疗两周后血清IL-18、VEGF、sVCAM-1较治疗前降低(P均＜0.05),且较正常对照组仍有升高趋势(P均＜0.05).结论 原发性肝癌患者血清IL-18、VEGF、sVCAM-1水平增高,可能与原发性肝癌的发生、发展及侵袭有关.     

p27^kip1及CyclinD1在肝细胞癌中的表达及意义

目的研究p27kipl和CyclinD1蛋白表达在肝细胞肝癌(HCC)中发生、发展中的作用.方法免疫组化S-P法检测40例HCC、15例肝硬化组织和5例正常肝组织石蜡标本p27kipl和CyclinD1蛋白表达.结果 p27kipl蛋白在HCC、肝硬化、正常肝组织表达阳性率分别为32.5%(13/40)、60%(9/15)、80%(4/5),p27kipl蛋白在HCC中表达与肝硬化和正常肝组织中表达比较有显著性差异(P＜0.05),p27kipl表达且与HCC的组织学分级、类型、淋巴结转移和生存期有统计学差异;CyclinD1蛋白在HCC、肝硬化、正常肝组织表达阳性率分别为57.5%(23/40)、46.67%(7/40)、40%(2/5),CyclinD1蛋白在HCC中表达与肝硬化和正常肝组织中表达比较无显著差异(P＞0.05),CyclinD1表达仅与HCC的组织学分级有统计学差异;p27kipl和 CyclinD1蛋白表达两者之间无相关性.结论 p27kipl和CyclinD1与HCC的发生、发展有着密切联系,两者独立地起作用;p27kipl蛋白在判断患者病情预后方面有较重要的价值.     

Chk2在原发性肝癌和肝非肿瘤组织中的表达

目的 探讨Chk2蛋白在肝非肿瘤组织和原发性肝癌组织中的表达差异,以及它在原发性肝癌组织中的表达与临床病理特征之间可能存在的关系.方法 应用免疫组化法检测15例肝非肿瘤组织(其中正常肝组织7例、肝硬化组织8例)和41例原发性肝癌组织Chk2蛋白的表达情况.结果 Chk2蛋白在原发性肝癌组织中表达阳性率为22.0％,在肝非肿瘤组织中表达阳性率为60％;Chk2在原发性肝癌组织中的表达低于肝非肿瘤组织中的表达,差异具有显著性(P＜0.05).Chk2蛋白在不同分化程度的原发性肝癌患者中的表达有差异,且差异有显著性(P＜0.05).结论 Chk2在肝非肿瘤组织中高表达,在原发性肝癌组织中为低表达;Chk2在原发性肝癌中的表达情况与分化程度相关.Chk2可能与原发性肝癌的发生、发展有关.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.