基质金属蛋白酶-9与卵巢上皮性癌血管生成关系的研究

目的探讨基质金属蛋白酶-9（MMP-9）在卵巢上皮性癌血管生成中的作用。方法采用免疫组织化学法（S-P法）检测75例卵巢上皮性癌组织中MMP-9的表达，并检测其中微血管密度（MVD）。结果卵巢癌组织和卵巢良性肿瘤中MMP-9阳性表达率明显高于正常卵巢组织（P〈0．01）。MMP-9在卵巢癌组织中表达与MVD显著正相关（r=0．286，P〈0．05）。结论MMP-9可能在卵巢上皮性癌血管生成中起重要作用，MMP-9表达增强，其血管生成能力可能显著增强，但并非唯一决定因素。检测卵巢上皮性癌中MMP-9表达对进一步了解卵巢上皮性癌局部血管生成情况有一定应用价值。     

基质金属蛋白酶-9及基质金属蛋白酶-2与卵巢上皮性癌血管生成的关系

目的探讨基质金属蛋白酶-9（MMP-9）及基质金属蛋白酶-2（MMP-2）在卵巢上皮性癌血管生成中的作用。方法采用免疫组织化学（SP法）检测75例卵巢上皮性癌组织中MMP-9及MMP-2的表达,并检测其中微血管密度（MVD）。结果卵巢癌组织和卵巢良性肿瘤中MMP-9及MMP-2阳性表达率明显高于正常卵巢组织（P〈0．01）。MMP-9及MMP-2在卵巢癌组织中表达与MVD显著正相关（r=0．286,P〈0．05）。结论MMP-9及MMP-2可能在卵巢上皮性癌血管生成中起重要作用,MMP-9及MMP-2表达增强,其血管生成能力可能显著增强,但并非唯一决定因素。检测卵巢上皮性癌中MMP-9表达对进一步了解卵巢上皮性癌局部血管生成情况有一定应用价值。     

卵巢肿瘤血清VEGF水平和肿瘤组织中MVD的检测

目的:探讨卵巢肿瘤血清血管内皮生长因子(VEGF)水平和肿瘤组织中微血管密度(MVD)的表达与其临床病理的关系.方法:对45例卵巢恶性肿瘤、18例卵巢良性肿瘤及12例正常卵巢对照采用ELISA法检测血清VEGF的水平以及LAB免疫组织化学法测定其MVD.结果:①恶性肿瘤患者血清VEGF水平明显高于良性肿瘤和正常卵巢组织(P＜0.05);上皮性癌中晚期癌(Ⅲ期、Ⅳ期)的血清VEGF水平明显高于早期癌(Ⅰ期、Ⅱ期);②恶性肿瘤卵巢组织中MVD明显高于良性肿瘤和正常卵巢组织(P＜0.05).结论:VEGF和MVD可能参与卵巢恶性肿瘤的演化过程,对判断卵巢肿瘤良恶性程度有一定临床意义;血清VEGF可能成为上皮性卵巢癌一种新的肿瘤标记物.     

Expression and significance of AQP1 and AQP3 in ovarian cancer

目的 探讨水通道蛋白1、3(AQP1、AQP3)在上皮性卵巢癌中的表达及其意义.方法 采用免疫组织化学方法检测上皮性卵巢良性、交界性、恶性肿瘤中肿瘤及腹膜组织中AQP1和AQP3的表达,同时检测血管内皮生长因子(VEGF)表达并以CD105标记各组织微血管内皮细胞测定微血管密度(MVD).结果 卵巢癌患者腹膜中AQP1、AQP3表达明显高于良性肿瘤者(P＜0.05).与卵巢肿瘤性质有关;卵巢癌患者中,有腹水(尤其是腹水量≥1000 ml)和淋巴结转移者AQP1、AQP3的表达明显高于无腹水者(P＜0.05).AQP3的表达与卵巢癌病理分期分级有关.结论 AQP1、AQP3参与卵巢癌发生发展、侵袭转移和腹水形成.腹膜组织上AQP1、AQP3的高表达与肿瘤盆腔扩散和腹水生成有密切关系.     

卵巢上皮性癌患者血清和腹水中血管上皮因子测定的临床价值

目的 测定卵巢上皮性癌患者血清和腹水中血管上皮生长因子(VEGF)的含量,探讨VEGF在卵巢上皮性癌的诊断、病情监测、预测复发中的价值.方法 采用酶联免疫吸附试验测定卵巢上皮性良性肿瘤(良性组)30例、交界性肿瘤(交界性组)7例、恶性肿瘤(恶性组)33例患者血清和腹水(或腹腔冲洗液)中VEGF的含量.结果 恶性组术前血清和腹水中VEGF的量明显高于交界性组和良性组(P＜0.05);交界性组、恶性组术后血清VEGF的量较术前明显下降(P＜0.05);恶性组Ⅲ～Ⅳ期术前血清VEGF的含量明显高于Ⅰ～Ⅱ期(P＜0.05),病理分级G2-G3的明显高于G1(P＜0.01);10例复发患者血清VEGF的含量明显高于23例未复发者(P＜0.05).结论 血清VEGF水平与卵巢上皮性癌的生长、预后有关,具有肿瘤标记物特性,可作为卵巢上皮性癌的诊断和病情监测指标.     

血清人附睾蛋白4对卵巢上皮性肿瘤的诊断价值

目的探讨卵巢上皮性肿瘤患者血清人附睾蛋白4(HE4)水平的变化,及联合检测血清中CA125和人附睾蛋白4(HE4)对卵巢上皮性肿瘤的临床价值。方法测定我院103例卵巢上皮性癌患者、47例交界性卵巢上皮性肿瘤患者、145例卵巢良性上皮性肿瘤患者血清HE4、CA125水平,分析联合HE4和CA125检测对卵巢上皮性癌的诊断价值。结果 HE4和CA125水平在卵巢良性上皮性肿瘤、交界性卵巢上皮性肿瘤、卵巢上皮性癌中平行升高,且组间差异均有统计学意义(P<0.05)。联合HE4和CA125检测较单项检测提高了对卵巢癌的灵敏度、特异性和临床符合率。结论 HE4可作为卵巢肿瘤新的标志物,与CA125联合检测来提高卵巢癌的诊断率。     

卵巢上皮性肿瘤中Galectin-3、VEGF的表达及意义

目的检测卵巢上皮性肿瘤中半乳糖凝集素-3(Galectin-3)与血管内皮生长因子(VEGF)的表达情况,探讨二者在卵巢上皮性肿瘤的发生发展中的作用及相关性。方法采用免疫组化SP法检测良性卵巢上皮性肿瘤组45例,交界性卵巢上皮性肿瘤组50例及恶性卵巢上皮性肿瘤组61例中Galectin-3、VEGF的表达情况。结果恶性卵巢上皮性肿瘤组中Galectin-3、VEGF的阳性表达率为67.2.%和70.5%,明显高于良性组及交界性卵巢上皮性肿瘤组,差异有统计学意义(P<0.05)。在恶性卵巢上皮性肿瘤中Galectin-3、VEGF的表达与肿瘤分期、组织分化程度及转移密切相关(P<0.05)。而与肿瘤的类型及肿瘤患者患病年龄状况无关(P>0.05)。Galectin-3与VEGF在恶性卵巢上皮性肿瘤组织中的表达呈正相关(r=0.739,P<0.05)。结论卵巢上皮性肿瘤中Galectin-3及VEGF的表达情况,在一定程度上反映卵巢肿瘤的恶性程度,与肿瘤的分期及预后密切相关,可能成为判断卵巢上皮性肿瘤性质及预后的参考指标。     

水通道蛋白在卵巢上皮癌中的表达及意义

目的探讨水通道蛋白1、3(AQP1、AQP3)在上皮性卵巢癌中的表达及其意义。方法采用免疫组织化学方法检测上皮性卵巢良性、交界性、恶性肿瘤中肿瘤及腹膜组织中AQP1和AQP3的表达,同时检测血管内皮生长因子(VEGF)表达并以CD105标记各组织微血管内皮细胞测定微血管密度(MVD)。结果卵巢癌患者腹膜中AQP1、AQP3表达明显高于良性肿瘤者(P<0.05)。与卵巢肿瘤性质有关;卵巢癌患者中,有腹水(尤其是腹水量≥1000ml)和淋巴结转移者AQP1、AQP3的表达明显高于无腹水者(P<0.05)。AQP3的表达与卵巢癌病理分期分级有关。结论 AQP1、AQP3参与卵巢癌发生发展、侵袭转移和腹水形成。腹膜组织上AQP1、AQP3的高表达与肿瘤盆腔扩散和腹水生成有密切关系。     

上皮性卵巢癌血管内皮生长因子表达及微血管密度

血管生成是影响实体瘤生长和转移的重要因素.我们采用免疫组织化学方法检测上皮性卵巢癌中血管内皮生长因子(VEGF)的表达及微血管密度(MVD),以了解上皮性卵巢癌血管生成情况,并探讨其与上皮性卵巢癌生物学行为之间的关系.     

p57KTP2与PCNA在卵巢上皮性肿瘤中表达及意义的研究

目的:研究细胞周期蛋白依赖性激酶抑制因子p57KIP2、增殖细胞核抗原(PCNA)在卵巢上皮性肿瘤中的表达及其相关性,以探讨其在卵巢上皮性肿瘤的发生、发展中所起的作用.方法:运用免疫组化S-P方法检测标本中p57KIP2、PCNA的表达情况,综合分析两者在卵巢上皮性肿瘤中的表达情况及其相关性.结果:恶性卵巢上皮性肿瘤中p57KIP2蛋白阳性表达率为13.75%,明显低于正常卵巢组织100%、良性卵巢上皮性肿瘤93.75%,其差别具有显著性(P＜0.05),057KIP2阳性表达率在恶性卵巢癌细胞临床Ⅰ期、Ⅱ期、Ⅲ期中分别为27.78%、5.88%、6.25%,其差别没有显著性;恶性卵巢上皮性肿瘤中PCNA蛋白阳性表达率为76.47%,明显高于正常卵巢组织10.00%、良性卵巢上皮性肿瘤18.75%,其差别具有显著性(P＜0.05).PCNA阳件表达率在恶性卵巢性肿瘤临床Ⅰ期、Ⅱ期、Ⅲ期中分别为55.56%、76.47%、100%,其差别具有显著性(P＜0.05);p5KIP2与PCNA表达具有明显相关性(P=0.0235＜0.05).结论:p57KIP2低表达和PCNA过度表达,可能参与恶性卵巢上皮性肿瘤的诱发;两者在卵巢上皮性肿瘤的发生及发展中可能有协同作用,同时在卵巢上皮性肿瘤的进展过程中两者有一定互馈关系.     

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.     

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.