骨形成蛋白（BMP—5）与IA型BMP受体在口腔鳞癌中的表达及意义

目的：认识和分析BMP及其受体BMPR-IA与口腔鳞癌发生、发展的可能关系。方法：用免疫组织化学方法分析BMP-5、BMP受体BMPR-IA在口号颊部粘膜正常上皮、慢性炎症和癌变中的表达，标本为18例正常上皮（normal buccal mucosa,NB)，24例慢性炎症（nonspecofic chronic inflammation.NCI)，58例鳞癌（squamous cell carcinoma,SCC)。结果：BMP-5、BMPR-IA在口腔粘膜的正常与慢性炎症上皮中有弱表达，NB与NCI明显差别；在鳞癌上皮中除2例BMP-5表达为阴性外，其余均有阳性或强阳性表达，明显高于NB、NCI两组；鳞癌中高分化、中分化、低分化三组间的表达无明显差别。结论：BMP-5、BMPR-IA可能参与对口腔鳞癌发生、发展的调控。     

全反式维甲酸对糖尿病大鼠肾脏组织BMP-7表达及细胞外基质代谢的影响

目的探讨全反式维甲酸（atRA）对糖尿病大鼠肾脏组织骨形成蛋白-7（BMP-7）、转化生长因子-β1（TGF-β1）表达和细胞外基质（E（M）Ⅳ、Ⅲ型胶原代谢的影响。方法随机选择24只舍SD大鼠制作糖尿病模型,其中12只入糖尿病模型（DM）组,另12只入糖尿病模型＋atRA（DM＋atRA）组,此外再随机选择12只正常大鼠作为空白对照（NC）组。分别于第8、12周末各组处死6只大鼠,通过光镜、电镜观察各组大鼠肾脏病理结果;通过免疫组织化学方法观察BMP-7,TGF-β1,Ⅳ、Ⅲ型胶原表达,并进行半定量分析;通过实时荧光定量PCR方法对TGF-β1 mRNA、BMP-7mRNA,进行相对定量分析。结果DM＋atRA组大鼠肾组织BMP-7表达较同时期DM组增加（P〈0.01）,主要表达于大鼠肾小管上皮细胞,而TGF-β1表达较同时期DM组减少（P〈0．01）：且DM＋atRA组大鼠肾组织ECM重要成分Ⅳ、Ⅲ型胶原表达与DM组相比较显著减少（P〈0．01）。同时观察到BMP-7蛋白与Ⅳ型胶原蛋白表达呈负相关（r=-0．75,P〈0．01）,与Ⅲ型胶原蛋白表达呈负相关（r=-0．71,P〈0．01）,与TGF-β1蛋白表达呈负相关（r=-0．86,P〈O．01）。荧光定量PCR结果表明,DM＋atRA组BMP-7mRNA水平升高,TGF-β1 mRNA水平下降,且两者星显著负相关（r=-0．83,P〈0．01）。结论atRA能减轻糖尿病大鼠肾脏病理损伤,延缓肾脏纤维化,这一防治作用可能与其增加BMP-7表达,下调TGF-β1表达从而减少肾组织ECM沉积有关。     

跟骨骨折不同分型治疗方案的选择

目的评价跟骨骨折根据不同分型选择不同治疗方案的临床效果。方法采用非手术治疗Ⅰ型跟骨骨折7例,闭合复位空心螺钉内固定术治疗Ⅱ型跟骨骨折7例,切开复位跟骨解剖型钛板内固定术治疗Ⅱ型跟骨骨折8例、Ⅲ型跟骨骨折16例、Ⅳ型跟骨骨折2例,距下关节融合术治疗Ⅳ型跟骨骨折2例。结果所收录病例治疗后均随访12个月以上,按照Mayland足部评分标准评价治疗效果：Ⅰ型优良率为100．0％,Ⅱ型优良率为93．3％,Ⅲ型优良率为83-3％,IV型优良率为16．7％。结论（1）跟骨骨折应根据不同分型选择相应治疗方案;（2）骨折分型越严重,治疗越复杂,疗效越差。     

大骨瓣减压治疗重型高血压基底节出血32例分析

目的 探讨大骨瓣减压清除血肿治疗重型高血压基底节出血的疗效。方法 32例基底节区出血，小于24小时，采用去骨瓣开颅经侧裂或颞叶皮层入路清除脑内血肿。结果 按ADL分级Ⅰ级2例，Ⅱ级6例。Ⅲ级12例，Ⅳ3例，Ⅴ级2例，死亡7例，生存率79．12％，良好率（Ⅰ～Ⅲ）62．5％。超早期良好率79．45％。结论 大骨瓣减压清除血肿治疗早期重型高血压基底节脑出血是行之有效的方法之一，超早期治疗能进一步提高患者的生存和生活质量。     

p14ARF和p53蛋白表达与脑胶质瘤发生发展的相关性研究

目的：探讨脑胶质瘤中p14^ARF和p53蛋白表达与不同病理级别脑胶质瘤的相关性及两者之间的相互作用。方法：应用免疫组织化学技术检测31例不同病理分级脑胶质瘤中的上述遗传学改变,5例脑挫裂伤脑组织为正常对照。结果：p14^ARF和p53蛋白在低级别（Ⅰ,Ⅱ级）和高级别（Ⅲ,Ⅳ级）脑胶质瘤中的表达阳性率分别为75．00％和30．43％,12．50％和69．57％。两蛋白在低级别和高级别中的表达差异均有显著性（P〈0.05）。p14^ARF表达水平与脑胶质瘤病理分级之间呈显著负相关性（r=0．571,P〈0．01）,即随着肿瘤恶性度的升高而降低。而突变型p53蛋白正相反,与病理分级呈显著正相关性（r=0．472,P≤0．01）,即随着肿瘤恶性度增高而增高。p14^ARF和p53蛋白之间在肿瘤中存在明显的相互作用（P〈0．05）。结论：p14^ARF和p53蛋白表达异常可导致细胞周期调控失常和细胞异常增殖,并且二者之间存在协同作用,可加速脑胶质瘤恶性演进。     

高压氧对人重组骨形成蛋白诱导骨形成的影响

目的：探讨高压氧疗法(HBOT)对人重组骨形成蛋白-2(rhBMP-2)诱导骨形成的活性的影响。方法：I型胶原作为rhBMP-2的载体，将1mg的rhBMP-2植入Wistar鼠小腿的肌袋内，30只鼠被随机分成HBO组和对照组。在材料植入3，7，21d时对新骨形成分别进行X线、生化分析及组织学检查。结果：21d时两组中均有新骨形成，但HBO组新骨形成明显高于对照组。7d时在HBO组植入材料的周边有软骨组织出现；同时，在7d和21d时HBO组碱性磷酸酶(ALP)活性和钙(Ca)含量明显高于对照组。结论：HBO加快了人重组骨形成蛋白-2(rhBMP-2)诱导骨形成的活性和速度。     

p14ARF蛋白与脑胶质瘤发生发展的相关性研究

目的探讨p14ARF蛋白与脑胶质瘤发生、发展及细胞生物学特性的关系,试图为脑胶质瘤发病机制的阐明及基因治疗提供新的理论依据和思路。方法选取68例不同级别的脑胶质瘤标本,用免疫组织化学法检测p14ARF蛋白表达的改变。结果p14ARF蛋白缺失率在Ⅰ～Ⅱ级为10.0%,Ⅲ级为25.0%,Ⅳ级为43.3%,p14ARF蛋白缺失率随脑胶质瘤恶性程度增高呈上升趋势(P<0.05)。结论p14ARF蛋白异常可导致细胞周期调控失常及细胞增殖活性升高,促进脑胶质瘤的恶性演进。     

脑胶质瘤中单酰甘油脂肪酶的表达及意义

目的 研究内源性大麻素代谢酶单酰甘油脂肪酶（monoacylglycerol lipase,MAGL）在脑胶质瘤组织中的表达情况及其与胶质瘤病理级别的关系,探讨其临床意义。方法 选取脑胶质瘤标本23例,其中WHO Ⅰ级1例,WHO Ⅱ级7例,WHO Ⅲ级5例,WHO Ⅳ级10例。对照组8例,均为脑挫裂伤后行内减压术切除的正常脑组织。应用实时荧光定量PCR（qRT-PCR）、LC-MS分别检测各组织标本中MAGL mRNA、MAGL活性的表达。结果 MAGL mRNA、MAGL活性在低级别（WHOⅠ~Ⅱ级）和高级别（WHOⅢ~Ⅳ级）脑胶质瘤组织中的表达水平较正常脑组织明显降低（P<0.01）,且随着肿瘤病理级别的增高而降低,与肿瘤的病理分级呈负相关（均P<0.01）。MAGL mRNA的表达水平与MAGL活性呈正相关。结论 MAGL可能参与了脑胶质瘤的发生、发展过程,检测MAGL的表达可评价脑胶质瘤的恶性程度。     

VEGF、bFGF、PCNA、p53在脑胶质瘤中的表达及临床意义

为探讨血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）、增殖性细胞核抗原（PCNA）和抑癌基因蛋白（p53）在脑胶质瘤中的表达及临床意义，采用免疫组织化学（S-P）法，检测120例标本中这4种蛋白因子的表达。结果表明，VEGF、bFGF、PCNA、p53在胶质瘤中的阳性率分别为70％、66．7％、77．5％和50％，并且随着胶质瘤病理分级递增，高级别组（Ⅲ～Ⅳ级）与低级别组（Ⅰ～Ⅱ级）相比差异有非常显著意义（P〈0．05）。结论：VEGF、bFGF、PCNA、p53的表达与胶质瘤的恶性进展有密切关系。     

脑胶质细胞瘤cyclin D1和Rb基因蛋白表达及临床意义

目的 通过检测脑胶质瘤中细胞周期调节蛋白 D1(cyclin D1)、视网膜母细胞瘤 ( Rb )基因蛋白表达,探讨 其在脑胶质瘤发生、生长和转移过程中,以及由低恶性度肿瘤向高恶性度肿瘤转化中的作用,为临床诊治和预后判断提供依据。方法 选用 54例Ⅰ～Ⅳ级星形细胞瘤手术后存档蜡块标本为实验标本,选用 6例正常脑组织为对照。应用流式细胞术( FCM 分别定量检测 cyclin D1、 基因蛋白表达量。结果 ① Cyclin D1蛋白在各级星形细胞瘤中表达均增强,且 ) Rb阳性率均为 100%,但 cyclin D1蛋白的表达量( 值) FI随肿瘤恶性度的升高而明显增加。Cyclin D1蛋白表达量 FI值与病理组织学分级有明显相关性(P <0.01)② Rb 蛋白表达量( 值)在Ⅰ级和Ⅱ级星形细胞瘤中表达增强,但随肿瘤恶性度 ; FI的升高而降低,且与病理组织学分级无显著相关性。Ⅰ级和Ⅱ级 Rb 蛋白表达量与Ⅲ级和Ⅳ级相比,则有显著性差异 (P<0.01) 。结论 ① Cyclin D1蛋白在各级星形细胞瘤中均为阳性表达,且表达量随肿瘤恶性度的升高而显著增加,说明cyclin D1可能通过加快细胞增殖周期和增强肿瘤细胞的侵袭性,参与了肿瘤的形成和恶性度的演化;② Rb 蛋白在高恶性度星形细胞瘤均有不同程度的表达缺失,说明 R b 表达缺失导致 cycl     

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.