大肠癌侵袭、转移螺旋CT征象与VEGF及iNOS表达间关系的研究

目的探讨大肠癌侵袭和转移螺旋CT征象与癌组织中VEGF及iNOS的表达以及两者之间的关系。方法对64例经手术病理证实且行螺旋CT平扫、动静脉期双期增强的大肠癌患者,观察每个病灶的浆膜侵犯和淋巴结转移情况。用免疫组化方法检测癌组织中VEGF及iNOS表达情况,并分析其与螺旋CT征象的关系。结果螺旋CT征象上肿瘤的浆膜侵犯、淋巴结转移与VEGF及iNOS蛋白表达有关（P〈0.05）。结论大肠癌侵袭和转移CT征象可以在一定程度上反映VEGF及iNOS的表达。     

血管内皮生长因子及受体FLT1在大肠癌中的表达及意义

目的探讨血管内皮细胞生长因子(VEGF)受体FLT1和血管生成及大肠癌发展的关系。方法应用免疫组织化学技术,检测102例大肠癌组织FLT1及VEGF蛋白表达和微血管密度(MVD),分析血管生成与大肠癌组织学分级、浸润深度、Dukes分期、淋巴结转移、肝转移和预后的关系。结果FLT1及VEGF阳性者MVD值显著高于阴性者(P<0.01)。FLT1、VEGF表达和MVD与大肠癌Dukes分期、淋巴结转移密切相关(P<0.01)。VEGF表达和MVD与肝转移相关(P<0.01),但FLT1与肝转移无关。FLT1及VEGF表达阳性或高MVD的大肠癌患者5年生存率较低(P<0.01)。VEGF表达与FLT1表达密切相关(P<0.01)。结论FLT1及VEGF与大肠癌的血管生成密切相关,对大肠癌的生长和浸润转移有促进作用。     

血管内皮生长因子受体KDR在大肠癌发展中的研究

目的探讨血管内皮细胞生长因子(vascularendothelialgrowthfactor,VEGF)受体KDR和大肠癌间质新生血管与大肠癌预后的关系。方法应用免疫组化方法监测86例大肠癌组织VEGF及KDR蛋白表达和微血管密度(Mi鄄crovesseldensity,MVD),分析VEGF、KDR和MVD及其与大肠癌Dukes分期、淋巴结转移的关系。结果VEGF及KDR阳性者MVD值显著高于阴性者(P<0.01),VEGF、KDR表达和MVD与大肠癌Dukes分期(P<0.01)、淋巴结转移(P<0.01)密切相关。结论KDR及VEGF与大肠癌的血管生成密切相关;对大肠癌的复发和转移有促进作用。KDR、VEGF和MVD可作为反映大肠癌生物学行为的客观指标。     

胃癌组织中HER-2表达及与血管生成的关系

目的探讨HER-2在胃腺癌组织中的表达及与血管生成的关系。方法采用免疫组化学法检测478例胃腺癌组织及49例癌旁组织中HER-2、VEGF和微血管密度(MVD)的表达。结果胃癌组织HER-2阳性表达率为10.9%(52/478),癌旁组织未见HER-2阳性表达,HER-2阳性表达与肿瘤部位、Lauren分型及分化程度显著相关(P0.05);VEGF在胃癌和癌旁组织中的阳性率分别为63.2%(302/478)和26.5%(13/49)(P0.01),VEGF表达与胃癌组织浸润深度、淋巴结转移、TNM分期、静脉侵犯显著相关(P0.05);MVD在胃癌组织与癌旁组织间有显著性差异[(51.44±19.24)vs(34.28±14.74),P0.01)],MVD与分化程度、浸润深度、淋巴结转移、TNM分期、静脉侵犯显著相关(P0.01)。胃癌组织中HER-2表达与VEGF、MVD均呈显著正相关(P0.01),VEGF表达与MVD呈显著正相关(P0.01)。结论 HER-2表达可能与胃癌血管生成有关,值得进一步研究。     

大肠癌增殖细胞核抗原及相关抗原表达的研究

目的探讨大肠癌增殖细胞核抗原(PCNA)表达、微血管密度(MVD)和血管内皮生长因子(VEGF)表达与肿瘤转移的关系。方法应用PCNA、CD34和VEGF抗体,采用免疫组化S-P法对38例大肠癌切片进行染色,并取10例正常组织对照。结果淋巴结转移组大肠癌PCNA、MVD、VEGF表达与非淋巴结转移组、正常对照组组间比较,差异均有显著性意义(P<0.01),且PCNA、MVD、VEGF表达两两呈正相关。结论PCNA、MVD、VEGF表达与淋巴结转移密切,三者均可作为预测大肠癌发生转移的指标。     

血管内皮生长因子与大肠癌淋巴转移关系的研究

目的探索大肠癌组织中血管内皮生长因子（VEGF）与大肠癌淋巴转移的关系。方法采用免疫组化方法检测40例大肠癌组织中VEGF的表达,采用CD34标记计数肿瘤组织微血管密度（MVD）,分析VEGF与大肠癌淋巴转移病理因素的关系,采用χ2检验、t检验和Spearman等级相关对应资料进行分析,显著性标准α=0.05。结果在合并有淋巴结转移的大肠癌组织中,VEGF阳性表达率、MVD值均高于无转移的大肠癌组织（P〈0.05）;在VEGF阳性表达的大肠癌组织中,MVD值明显高于VEGF阴性表达组织,且MVD值与VEGF的表达呈正相关（P〈0.05）。结论 VEGF可能促进大肠癌的血管生成,进而促进大肠癌的转移。     

血管内皮生长因子和环氧合酶在大肠癌中的表达及其意义

目的探讨血管内皮生长因子(VEGF)和环氧合酶-2(COX-2)在大肠癌患者中的表达及其临床意义。方法采用免疫组化SP法检测56例大肠癌组织和20例癌旁组织以及20例正常黏膜中VEGF和COX-2表达及微血管密度(MVD),结合病理及临床资料进行统计学分析。结果大肠癌组织中的VEGF和COX-2的表达阳性率明显高于癌旁组织和正常黏膜组织,与正常黏膜组织中阳性表达率存在显著差异性(P<0.05)。VEGF和COX-2阳性者MVD值显著高于阴性者(P<0.05),VEGF和COX表达和MVD与有无淋巴结转移、有无肝转移及Dukes分期密切相关。结论VEGF和COX-2在大肠癌组织中呈共同表达,COX-2、VEGF高表达可能通过促进血管形成对大肠癌的发生、发展起重要作用,VEGF、COX-2和MVD可作为大肠癌判断预后和指导治疗的有效指标。     

血管内皮生长因子在胃癌中的表达及其意义

目的　探讨血管内皮生长因子 (VEGF)在胃癌中的表达及其与血管生成、细胞增殖关系。方法　应用免疫组织化学法检测 4 2例胃癌组织VEGF的表达、增殖细胞核抗原 (PCNA)表达和微血管密度 (MVD)。结果　VEGF表达和MVD与肿瘤大小、浸润深度、淋巴结转移有关 (P <0 0 5 ) ,PCNA表达与肿瘤分化、淋巴结转移有关 (P <0 0 5 )。VEGF阳性组MVD显著高于VEGF阴性组 (P <0 0 1) ,VEGF阳性组PCNA表达显著高于VEGF阴性组 (P <0 0 5 )。结论　VEGF与胃癌的血管生成密切相关 ,对胃癌的增殖、浸润和转移起促进作用 ,检测VEGF表达可作为胃癌的预后指标之一。     

血管内皮生长因子及受体FLTl在大肠癌中的表达及意义

目的探讨血管内皮细胞生长因子（VEGF）受体FLTl和血管生成及大肠癌发展的关系。方法应用免疫组织化学技术，检测102例大肠癌组织FLTl及VEGF蛋白表达和微血管密度（MVD），分析血管生成与大肠癌组织学分级、浸润深度、Dukes分期、淋巴结转移、肝转移和预后的关系。结果FLTl及VEGF阳性者MVD值显著高于阴性者（P〈O．01）。FLT1、VEGF表达和MVD与大肠癌Dukes分期、淋巴结转移密切相关（P〈0．01）。VEGF表达和MVD与肝转移相关（P〈0．01），但FLTl与肝转移无关。FLTl及VEGF表达阳性或高MVD的大肠癌患者5年生存率较低（P〈O．01）。VEGF表达与FLTl表达密切相关（P〈O．01）。结论FLTl及VEGF与大肠癌的血管生成密切相关，对大肠癌的生长和浸润转移有促进作用。     

VEGF在甲状腺肿瘤中的表达及与肿瘤血管生成的关系

目的探讨VEGF在甲状腺肿瘤组织中的表达及其与肿瘤血管生成的关系。方法应用免疫组织化学Envision法检测140例甲状腺癌组织、50例甲状腺腺瘤及30例正常甲状腺组织中VEGF的表达,并检测肿瘤微血管计数(MVD),分析VEGF蛋白的表达与肿瘤血管生成的关系。结果甲状腺癌组织中VEGF阳性表达和MVD计数均明显高于正常甲状腺和甲状腺腺瘤组织(P0.05)。在甲状腺癌组织中有颈部淋巴结转移、AJCC分期Ⅲ～Ⅳ及浸润达包膜或包膜外者的VEGF表达及MVD计数明显高于无颈部淋巴结转移、AJCC分期I～Ⅱ及未突破包膜者(P0.05)。甲状腺癌组织中VEGF表达及MVD值之间呈显著正相关(r=0.564,P0.05)。结论 VEGF和MVD计数可作为辅助甲状腺肿瘤早期鉴别诊断和预测甲状腺癌浸润、转移和预后的参考指标。     

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.     

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.     

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.     

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.