生存素在大肠癌中的表达及其与血管生成的关系

目的研究生存素(survivin)在大肠癌组织中的表达及其与血管生成的关系。方法应用RT-PCR方法检测52例大肠癌组织,48例癌旁正常粘膜组织中生存素mRNA的表达,序列分析验证PCR扩增的正确性;用免疫组织化学法检测52例大肠癌组织中生存素蛋白、凋亡指数(AI)、增殖指数(LI)和微血管密度(MVD)。结果大肠癌组织中生存素mRNA阳性表达率为67.3%,而癌旁正常组织阳性表达率为25.0%(P<0.01);生存素mRNA表达与大肠癌患者性别、肿瘤大小、病理类型、淋巴结转移、远处转移及临床分期无明显相关关系。序列分析结果:所扩增生存素与人生存素序列具有99%的同源性。免疫组化检测显示大肠癌组织中生存素蛋白阳性表达率为51.9%(27/52)。生存素表达阳性组的凋亡指数为(0.67±0.18)%,显著低于生存素表达阴性组(1.14±0.42)%,(P<0.01);生存素表达阳性组的LI(51±22)%,MVD(21.4±8.2),显著高于生存素表达阴性组的(27±18)%,(P<0.01)和(14.2±5.4)(P<0.05)。结论(1)生存素表达与大肠癌患者性别、肿瘤大小、病理类型、淋巴结转移、远处转移及临床分期无明显相关关系。生存素抑制凋亡和促进增殖可能是参与大肠癌发生的重要机制。(2)生存素与大肠癌血管生成关系密切。     

不稳定心绞痛患者的血浆可溶性选择素水平升高

Enver　Atalar等进行一项研究以确定不稳定心绞痛(UA)患者的可溶性E-选择素、P-选择素和L-选择素是否增高。 作者们在此项研究取23例UA患者、26例稳定心绞痛(SA)患者和15例冠状动脉造影正常的对照患者的外周血液,应用酶联免疫试验测定可溶性E-、P-和L-选择素 结果:UA患者的可溶性E-选择素水平[(45±11)ng/ml]明显高于对照者[(30±8)ng/ml,P<0.001],或SA患者[(34±8)ng/ml,P=0.001]。UA患者血浆P-和L-选择素水平[分别为(421±144)ng/ml和(772±160)ng/ml]同样明     

狼疮性肾炎患者外周血细胞间黏附分子-1和P-选择素的表达

目的 观察细胞间黏附分子-1(ICAM-1)和P-选择素在狼疮性肾炎(LN)患者外周血中的表达水平.方法 用ELISA方法分析了36例LN患者和11例正常人外周血ICAM-1和P-选择素表达情况.结果 LN患者外周血ICAM-1和P-选择素表达与正常对照组比较有明显差异(P＜0.05).结论 ICAM-1和P-选择素表达与LN的病变有一定相关性.     

血小板P-选择素与冠状动脉病变严重程度的相关性研究

目的探讨血小板P-选择素和冠心病患者冠状动脉病变严重程度的关系。方法选取2006年1月至12月在我院心内科因胸痛住院患者91例,其中急性心肌梗死(AMI)5例,稳定型心绞痛(SA)36例,不稳定型心绞痛(UA)50例。所有患者均行选择性冠状动脉造影,显示至少1支血管狭窄≥50%诊断为冠状动脉粥样硬化性心脏病。选取同期冠状动脉造影正常的住院患者17例作为对照。检测患者血小板P-选择素表达的阳性率。根据冠状动脉造影结果评价冠状动脉狭窄程度、范围并进行Gensini评分,评估冠状动脉病变严重程度。结果同对照组相比,冠心病患者的血小板P-选择素表达阳性率显著高于对照组[(3.5±2.2)%vs(2.4±1.0)%,P=0.046],并且同反映冠状动脉病变严重程度的Gensini积分有相关性(r=0.701,P<0.05)。结论冠心病患者血小板P选择素的表达同冠状动脉病变严重程度有相关性。     

卡介菌多糖核酸对生殖器疱疹病人血CD4~+T细胞细胞因子表达影响

目的:研究卡介菌多糖核酸(BCG-PSN)对复发性生殖器疱疹(RGH)病人外周血CD4+T细胞内白细胞介素12(CD4+T-IL-12),干扰素γ(IFN-γ),白细胞介素4(IL-4)表达的影响。方法:用流式细胞仪检测30例经BCG-PSN治疗、15例未予BCG-PSN治疗的RGH病人与15名正常人外周血CD4+T-IL-12,IFN-γ和IL-4表达。结果:治疗前RGH病人外周血CD4+T-IL-12,IFN-γ表达较正常组下降[(1.8±s0.5)%vs(3.3±1.9)%,(3.5±2.6)%vs(5.3±1.5)%;P<0.01],IL-4表达上升[(3.0±0.5)%vs(2.2±0.8)%,P<0.01]。治疗后BCG-PSN组外周血CD4+T-IL-12和IFN-γ水平升高[(3.1±1.6)%vs(1.8±0.5)%,P<0.01;(5.0±2.6)%vs(3.6±2.6)%,P<0.05],IL-4表达下降[(2.4±0.5)%vs(3.0±0.5)%,P<0.01],Th1/Th2恢复正常。结论:RGH病人存在Th1/Th2失衡和IL-12表达低下;BCG-PSN通过诱导外周血CD4+T-IFN-γ,IL-12表达,下调IL-4表达,纠正病人免疫紊乱而提高临床疗效和预防复发。     

血尿酸检测在妊娠期高血压疾病中的意义

目的探讨妊娠高血压患者血清尿酸(UA)水平测定的意义及临床价值。方法随机抽取2010年1月至2011年4月在我院产检和分娩的妊娠高血压孕妇80例作为观察组,其中轻度32例,中度27例,重度21例;另抽取同期我院正常妊娠妇女50例作为对照组;分别对两组血清尿酸(UA)水平进行测定。结果观察组UA水平为(364.7±96.5)μmol/L,对照组为(230.6±53.8)μmol/L,两组比较,差异有统计学意义(P<0.01);轻度妊娠高血压患者UA水平为(296.5±59.2)μmol/L,中度妊娠高血压为(356.0±69.9)μmol/L,重度妊娠高血压为(473.8±93.3)μmol/L。中度妊娠高血压患者UA水平明显高于轻度妊娠高血压,差异有统计学意义(P<0.01);重度妊娠高血压UA水平明显高于中度及轻度妊娠高血压,差异有统计学意义(P<0.01)。结论妊娠高血压病情严重程度与UA水平密切相关,动态监测血清UA水平的变化,对妊娠高血压的诊断和预后有十分重要的临床意义。     

IL-6与P-选择素在非小细胞肺癌中的表达及临床意义

目的 探讨IL-6与P-选择素在非小细胞肺癌中的表达及其临床意义.方法 ELISA和免疫组化检测50例术前、术后3周内非小细胞肺癌患者外周血中IL-6与P-选择素的水平以及术后癌组织中和癌旁组织中的表达.结果 (1)肺组织中的IL-6表达明显高于癌旁组织(P<0.05)与吸烟指数和病情严重程度有关(P<0.05),与肿瘤大小和组织分型无关(P>0.05),免疫组化阳性表达者血清IL-6水平明显高于阴性患者;术后外周血IL-6与P-选择素的浓度明显低于术前,差异具有统计学意义(P<0.05).(2)肺组织中的P-选择素表达明显高于癌旁组织(P<0.05),只与病理分期和组织类型有关(P<0.05),免疫组化阳性表达者血清P-选择素水平高于阴性患者,但差异无统计学意义(P>0.05).(3)非小细胞肺癌患者外周血中IL-6与P-选择素的水平没有明显的相关性(r=0.424,P>0.05).结论 非小细胞肺癌患者体内存在的IL-6,P-选择素的高表达与肿瘤的发生发展有关;血清中升高的IL-6可能来源于肺癌肿瘤组织中IL-6的高表达.     

近红外光谱仪对妊娠高血压母亲之新生儿脑损伤的早期预测价值

目的:探讨母体妊娠高血压对新生儿脑组织氧饱和度的影响,及近红外光谱仪(NIRS)在妊娠高血压母亲的新生儿脑损伤的早期预测价值。方法:对2005年3月￣2006年3月间在我院NICU住院的38例产自妊娠高血压母亲的新生儿和30例正常新生儿(对照组)在出生后12小时内,应用NIRS监测其脑组织氧饱和度,并将监测结果与脑损伤程度进行相关性分析。结果:妊娠高血压母亲组新生儿脑组织氧饱和度(64.3±4.3)%和正常对照组新生儿脑组织氧饱和度(71.2±5.9)%,差异有显著性(P<0.01);有脑损伤组新生儿与无脑损伤组新生儿脑组织氧饱和度分别为(61.7±2.3)%和(67.5±5.9)%,P<0.01。结论:母亲妊娠高血压可导致新生儿脑组织氧饱和度的异常,及早应用NIRS监测脑组织氧饱和度能早期预测脑损伤的发生。     

系统性红斑狼疮患者外周血V_α24-V_βⅡ自然杀伤T细胞致病性的研究

目的研究系统性红斑狼疮(SLE)患者外周血Vα24-Vβll自然杀伤T细胞(NKT)细胞数量变化和功能状态在致病中的作用。方法采用流式细胞仪检测32例SLE患者和30名正常对照组Vα24-Vβ11NKT细胞数量以及体外活化前后表达血细胞分化抗原(CD)69和白细胞介素-4(IL—4)、Ⅱ型干扰素(IFN-γ)的水平。结果SLE患者外周血Vα24-Vβ11NKT细胞数量(0.4%±0.25%)低于正常对照组(1.07%±0.23%,P<0.01),NKT细胞体外活化前CD69表达为5.26%±2.12%,正常对照组为11.47%±2.86%(P<0.05);活化后表达CD69为56.61%±0.47%,正常对照组为96.71%±0.33%(P<0.01)。SLE患者NKT细胞活化前其胞浆内IL-4含量为32.46±5.49pg/ml,正常对照组为12.21±3.31pg/ml,活化后其胞浆内IL-4含量为48.38±8.53pg/ml,正常对照为26.93±6.84pg/ml(均P<0.05),而IFN-γ,含量活化后为19.32±6.45pg/ml,正常对照组为33.65±11.91pg/m1(P<0.05)。结论SLE发病可能与NKT细胞数量的低下及功能严重失调相关。     

妊娠高血压综合征患者内皮素含量与脐血管内皮细胞损伤的关系

为探明妊娠高血压综合征时血管内皮细胞损伤与内皮素释放的定量关系 ,对 39例妊娠高血压综合征和 1 7例正常妊娠胎儿脐动脉内皮细胞损伤程度进行定量观察 ,并结合免疫组化和放射免疫法对内皮细胞内内皮素及母血、胎儿脐动脉血内皮素水平进行定量分析。结果 ,妊娠高血压综合征组母血及胎儿脐动脉血内皮素水平分别为 ( 3.36± 0 .62 )ng/L和 ( 8.1 4± 1 .58)ng/L ,均显著高于正常妊娠组的( 2 .68± 0 .51 )ng/L和 ( 6.1 4± 1 .37)ng/L( P <0 .0 1 ) ;妊娠高血压综合征组内皮细胞内IgG和内皮素阳性率分别为 ( 2 .69± 0 .35) %和 ( 3.2 6± 0 .2 9) % ,也均显著高于正常妊娠组的 ( 2 .0 1± 0 .2 4 ) %和 ( 2 .38±0 .2 6) % (P <0 .0 5)。提示妊娠高血压综合征者血管内皮细胞损伤加重 ,内皮细胞合成、释放内皮素增多 ,导致血压进一步升高。     

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.     

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.     

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.