肝细胞肝癌组织中促红细胞生成素受体的表达及其与微血管密度的相关性研究

目的探讨肝细胞肝癌（HCC）微血管密度（MVD）与促红细胞生成素受体（EPOR）表达之间的关系,以及此二者与临床病理学特征之间的关系。方法应用免疫组织化学法检测46例HCC、20例肝硬化和10例正常肝组织内EPOR的表达情况,观察与HCC病理学特点及MVD之间的关系。结果（1）EPOR及MVD值在HCC中的阳性表达率和强度显著高于肝硬化和正常肝脏组织（P〈0.05）;（2）EPOR在有包膜侵犯组、低分化组及有转移HCC中的阳性表达率及强度明显高于无包膜侵犯组（χ^2=6.40,P〈0.05;）、高中分化组（χ^2=12.03,P〈0.01）;以及无转移组（χ^2=5.62,P〈0.05）;（3）肝癌〉5cm、有包膜侵犯、有转移、低分化组的MVD值明显高于肝癌≤5cm（t=2.82,P〈0.05）、无包膜侵犯（t=3.91,P〈0.05）、无转移（t=4.10,P〈0.05）及高中分化组（t=5.12,P〈0.05）;（4）EPOR阳性表达HCC中的MVD值明显高于EPOR阴性表达HCC中的MVD值（t=5.43,P〈0.05）。结论EPOR在HCC组织中的表达上调与其血管生成和浸润转移有关。     

肝癌中血管生成素2和血管内皮生长因子的表达及其临床意义

目的观察血管生成素2（Ang-2）和血管内皮生长因子（VEGF）在肝癌组织中的表达,探讨它们与肿瘤的血管发生、入侵／转移能力和肝细胞性肝癌（HCC）预后之间的关系。方法采用免疫组织化学的方法检测肝癌组织中Ang-2和VEGF的表达,并通过对CD34的免疫组化染色检测肿瘤的微血管密度（MVD）。结果肝癌组织Ang-2表达和病理学分期、门静脉侵犯明显相关（P〈0．05）。VEGF和Ang-2均表达阳性时肝癌组织中MVD显著上调,且预后较差（P〈0.05）。结论肝癌Ang-2和VEGF的共同表达能诱导肿瘤血管发生,并和肝癌的入侵与恶性程度以及预后有关。     

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。     

胃癌组织PTEN蛋白、VEGF表达和血管形成的关系

目的研究胃癌组织中PTEN蛋白、血管内皮生长因子（VEGF）表达和血管形成的关系。方法采用免疫组织化学S-P法检测20例正常胃黏膜及80例胃癌组织中PTEN、VEGF、微血管密度（MVD）的表达。结果20例正常胃黏膜组织PTEN全部阳性表达，胃癌组织PTEN阳性率为52．5％（40／80）、PTEN蛋白表达水平与组织分化程度、淋巴结转移及TNM分期密切相关（P〈0．05），VEGF在正常胃黏膜阳性率为10％（2／20），胃癌组织阳性率为53．8％（43／80），二者差异有显著性（P〈0．01），VEGF表达与淋巴结转移及TNM分期密切相关（P〈0．05），胃癌组织MVD显著高于正常胃黏膜MVD（P〈0．01），MVD与胃癌组织浸润深度、分化程度、淋巴结转移及TNM分期密切相关（P〈0．01），胃癌组织中VEGF表达与MVD呈显著正相关（P〈0．01），PTEN蛋白表达水平与VEGF表达呈显著负相关（P〈0．01），PTEN蛋白表达水平与MVD呈显著负相关（P〈0．01）。结论PTEN蛋白表达与胃癌的临床病理特征密切相关，胃癌PTEN基因失活可能通过增加VEGF的表达来促进血管形成，导致肿瘤恶性进展。     

NF-kB p65、VEGF在肝细胞癌中的表达及临床意义

目的探讨核转录因子kB（NF-kB）p65蛋白和血管内皮生长因子（VEGF）在肝癌组织中的表达及临床意义。方法用免疫组化sP法研究HCC30例、肝硬化组织10例和正常肝组织6例中NF-kBp65、VEGF的表达。结果HCC组织中,VEGF的表达与包膜完整、肝内血管癌栓及淋巴结转移相关（P〈0．05）,而与年龄、性别、肿瘤大小、结果数目、组织病理学分级及肝硬化背景无关（P〉0．05）;NF-kBP65表达与肿瘤大小、组织病理学分级、肝内血管癌栓及淋巴结转移（P〈0．05）相关,而与年龄、性别、结果数目、包膜完整、肝硬化背景无关（P〉0．05）;NF-kBP65与VEGF表达呈正相关（r=0．962,P〈0．01）。VEGF在HCC癌旁组织中表达最高,而NF-kBp65以HCC组织表达最高。结论NF-kBp65介导的VEGF异常表达可能在肝癌发生、进展和转移中独立发挥作用。     

大肠癌中环氧化酶-2和生存素的表达与肿瘤血管生成的关系

目的：探讨大肠癌中环氧化酶-2（COX-2）、生存素（Survivin）的表达及二者与微血管密度（MVD）的关系。方法：应用免疫组织化学S—P法检测48例大肠癌中C0X-2、Survivin以及MVD（采用CD34标记）的表达情况，将其在大肠癌中的表达情况与临床病理指标的关系进行了统计分析。结果：（1）COX-2和Survivin在大肠癌中的表达与Dukes分期有关（P〈0．05）。（2）COX-2与Survivin在大肠癌中的表达呈正相关（r-0．318，P〈0．05）。（3）大肠癌中COX-2、Survivin表达阳性组的MVD值高于表达阴性组（P〈0．01）；Survivin，COX-2表达共同阳性组的MVD值高于共同阴性组（P〈0．01）。结论：COX-2和Survivin在大肠癌的发生和发展中起了重要作用，并可能协同促进了大肠癌血管的形成。     

神经母细胞瘤血管内皮细胞生长因子、Ki-67抗原表达及微血管密度研究

目的 探讨血管内皮细胞生长因子（VEGF）、瘤内微血管密度（MVD）与神经母细胞瘤（NB）细胞增殖及预后的关系。方法 采用S-P免疫组化法，检测VEGF、CD34和Ki-67抗原在21例NB中的表达及MVD计数。结果 VEGF及Ki-67表达与NB病理分型及核分裂指数有关（P〈0．05或P〈0．01），而与NB分化与否、肿瘤大小及性别无关。MVD值在临床各病理参数间差异无显著意义。VEGF表达与MVD值、VEGF与Ki-67表达呈明显正相关（P〈0．01）。结论 VEGF、Ki-67表达与NB细胞增殖及预后密切相关。     

促血管生成素-2（Ang-2）在非小细胞肺癌（NSCLC）中的表达与肿瘤血管生成的关系

目的检测促血管生成素-2（Ang-2）在非小细胞肺癌（NSCLC）中的表达，研究它与血管内皮生长因子（VEGF）表达及微血管密度（MVD）的关系，探讨其在非小细胞肺癌血管生成中的作用。方法用免疫组化法检测37例非小细胞肺癌组织及15例癌旁正常组织中Ang-2、VEGF及CD34相关抗原的蛋白表达情况，分析各个指标在各组表达的差异，研究各个指标的相互关系。结果非小细胞肺癌组织中Ang-2表达阳性率、VEGF记分和微血管密度计数（MVD）均明显高于癌旁正常组织；Ang-2表达与VEGF和MVD表达有明显相关性（r分别0．509和0．615，P〈0．05）；非小细胞肺癌中Ang-2表达阳性者与Ang-2表达阴性者相比，VEGF记分和MVD显著不同（P〈0．05）；Ang-2表达与非小细胞肺癌的淋巴结转移及肿瘤的分级有关（P〈0．05）。结论Ang-2与非小细胞肺癌的浸润、进展密切相关；其对非小细胞肺癌肿瘤血管生成有促进作用，这种作用具有明显的VEGF依赖性。     

环氧化酶-2在乳腺癌中的表达及其临床意义

目的研究环氧化酶-2（COX-2）在乳腺癌组织中的表达及其与微血管密度（MVD）、血管内皮生长因子（VEGF）之间的关系,初步探讨COX-2对乳腺癌发生发展的作用及临床意义。方法选择146例乳腺癌标本,应用免疫组织化学染色方法（SP法）检测标本中COX-2、VEGF的表达和CD34标记的MVD值。结果 146例中,COX-2表达阳性114例（78.1%）,高表达70例（47.9%）。COX-2表达程度与患者年龄、肿瘤直径及HER-2/neu表达程度无关（P〉0.05）,与腋淋巴结转移状况和肿瘤分期有关（P〈0.01）,与VEGF表达程度及MVD值明显相关。COX-2高表达组的MVD值高于低表达组,差异有统计学意义（P〈0.01）。结论 COX-2的高表达在乳腺癌的发生发展中起重要的作用,其能促进乳腺癌新生血管的形成,进而影响乳腺癌的发展和转归。     

血管内皮生长因子在恶性骨肿瘤中的表达及其与转移的关系

应用免疫组化方法对21例恶性骨肿瘤进行血管内皮细胞生长因子（VEGF）的免疫检测和血管计数。发现在10例有转移的恶性骨肿瘤中有7例为阳性，且多为强表达；11例无转移的恶性骨肿瘤中有4例为阳性，且多为弱表达（P＜0．05）。在5例强表达者中，有4例发生转移；而在3例弱表达者中只有1例发生转移。肿瘤的血管计数表明：转移组肿瘤微血管数高于无转移组（P＜0．05）。VEGF蛋白阳性组肿瘤血管数高于VEGF蛋白阴性组（P＜0．01）。     

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.