T淋巴细胞上Fas抗原的表达与系统性红斑狼疮活动的相关性研究

目的　观察T淋巴细胞亚群上Fas抗原的表达与系统性红斑狼疮 (SLE)抗体的产生及疾病活动的相关性。方法　通过流式细胞仪 ,采用微量全血直接双标记免疫荧光染色方法 ,对 30例活动期SLE患者及 15名正常人外周血CD3+ 、CD4+ 、CD8+ 淋巴细胞亚群上Fas抗原进行检测。结果　活动期SLE患者外周血CD3+ 、CD4+ 、CD8+ 淋巴细胞亚群上Fas抗原的表达较正常人明显上调 (P <0 0 1) ;Fas抗原的表达与SLE的活动性呈正相关 (r =0 815 ,P <0 0 0 1) ;全部患者中有 19例抗dsDNA抗体阳性 ,抗dsDNA抗体 (+)患者组T淋巴细胞上Fas抗原的表达较抗dsDNA抗体 (- )组高 (P <0 0 5 )。结论　SLE患者T淋巴细胞表面Fas抗原表达上调 ,由Fas介导的淋巴细胞凋亡加快 ,刺激机体产生抗dsDNA等多种自身抗体。Fas抗原表达异常是引起SLE免疫功能紊乱的原因之一。Fas抗原的表达与SLE的活动性呈正相关 ,可为判断狼疮的活动提供参考     

胸腺五肽对严重烧伤小儿的免疫调节作用

目的　调查胸腺五肽 (thymopentin ,TP 5 )对严重烧伤小儿T淋巴细胞亚群及NK细胞的影响。 方法　分别检测治疗组 (2 0例 )和对照组 (2 0例 )病人伤后 2、5、10、17d外周血T淋巴细胞亚群及NK细胞 ,治疗组病人从伤后第 2天起接受TP 5治疗 ,1mg/d ,肌肉注射 ,疗程 15d ;对照组不给予TP 5。 结果　烧伤后第 2天二组病人T淋巴细胞及NK细胞差异无显著性 ;烧伤后 5、10、17d二组病人T淋巴细胞总数差异无显著性 ,对照组CD8+细胞显著高于治疗组 (P <0 0 1) ,对照组CD4 + /CD8+ 比值显著低于治疗组 (P <0 0 1) ;治疗组NK细胞在伤后 5、10、17d均高于对照组 (P <0 0 5 )。结论　胸腺五肽能明显提高和改善严重烧伤小儿T淋巴细胞及NK细胞功能 ,可作为一种良好的免疫调节剂     

术后硬膜外镇痛对机体免疫功能的影响

目的　测定围术期外周血T淋巴细胞亚群的变化 ,旨在探讨术中及术后连续硬膜外镇痛对免疫功能的影响。方法　 3 2例病人随机分为 4组 ,每组 8例。Ⅰ组在全麻下、Ⅱ组在全麻复合硬膜外麻醉下行上腹部胃癌根治术 ,Ⅲ组在全麻下、Ⅳ组在全麻复合硬膜外麻醉下行下腹部全子宫切除术 ,Ⅱ、Ⅳ组术后连续硬膜外镇痛 4 8h。分别于手术日晨 ,手术切皮后 1h ,术后第 1、3、7d晨抽取患者肘部静脉血 ,测定T淋巴细胞亚群CD3+(总T淋巴细胞 )、CD4+(辅助性 /诱导性T淋巴细胞 )和CD8+(抑制性 /杀伤性T淋巴细胞 )及C 反应蛋白 (CRP)浓度。结果　Ⅰ组术后第 1d、第 3dCD4+、CD8+比术前显著下降(P <0 .0 1) ;Ⅱ组、Ⅲ组各时间点T淋巴细胞亚群无显著改变 (P >0 .0 5 ) ;Ⅳ组术后第 1dCD4+表达受抑 (P <0 .0 1)。上腹部手术 (Ⅰ、Ⅱ组 )较下腹部手术 (Ⅲ、Ⅳ组 )CRP显著升高 (P <0 .0 5 )。结论　上腹部手术应激反应明显 ,术中、术后硬膜外镇痛可减轻应激反应 ,有利于细胞免疫功能的稳定 ;下腹部手术应激反应轻 ,细胞免疫功能无显著改变 ,术后硬膜外镇痛无助于机体免疫功能的维护。     

慢活肝患者外周血T淋巴细胞亚群和循环免疫复合物测定的临床意义

目的 :为探讨T淋巴细胞亚群和CiC在慢性活动性乙型肝炎患者中免疫功能的变化。方法 :采用红细胞玫瑰花环法和聚乙二醇沉淀法 ,对 32例CAH患者、18例健康献血者的外周血T淋巴细胞亚群及CiC进行检测。结果 :CAH患者CD4+ 细胞、CD4+ /CD8+ 比值明显低于对照组 (P <0 0 1) ,CD8+ 细胞、CiC值明显高于对照组 (P <0 0 1)。结论 :外周血T淋巴细胞亚群及CiC的检测对CAH患者的肝细胞损伤及细胞免疫功能的监测有一定参考价值     

恶性胸腔积液患者T淋巴细胞亚群的检测及临床意义

目的　观察恶性胸腔积液患者胸腔内注射顺铂 (DDP)前、后T淋巴细胞亚群的变化。方法　 30例确诊的恶性胸腔积液患者 ,尽量排尽胸腔积液后 ,胸腔内注入生理盐水 2 0ml +顺铂 4 0mg ,每周给药 1次 ,连用 1～ 3次 ,治疗前及其后 1个月分别查血T淋巴细胞亚群 ,并与正常对照组比较。结果　恶性胸腔积液患者治疗前、后CD+ 3 、CD+ 4 、及CD+ 4 /CD+ 8明显低于正常 (P<0 0 5～ 0 0 1 ) ,CD+ 8明显升高 (P <0 0 1 ) ,而治疗后 ,除CD+ 8降低显著外 (P <0 0 5 ) ,其余指标与治疗前比较差异无显著性 (P>0 0 5 )。结论　T淋巴细胞亚群测定对恶性胸腔积液的诊断、治疗及预后估计有一定价值     

杂色曲霉素对小鼠胸腺和脾脏转录因子Foxp3~+调节性T淋巴细胞的影响

目的探讨杂色曲霉素(ST)对机体免疫调节功能的影响。方法BALB/c小鼠随机分为正常对照组、溶剂对照组、ST3,30,300和3000μg·kg-1组。小鼠ip给药24h后,处死取胸腺和脾脏,采用流式细胞术测定胸腺和脾脏细胞中CD4+和CD8+T淋巴细胞及转录因子Foxp3阳性(Foxp3+)调节性T淋巴细胞的百分率,免疫组织化学法检测胸腺和脾脏组织中Foxp3+调节性T淋巴细胞数量,Western蛋白印迹法和RT-PCR分别测定胸腺和脾脏组织中Foxp3蛋白和mRNA的表达。结果溶剂对照组与正常对照组比较,小鼠胸腺和脾脏CD4+,CD8+和Foxp3+T淋巴细胞百分率均无明显差异。与溶剂对照组比较,ST3μg·kg-1组胸腺CD8+T淋巴细胞百分率降低,ST3和30μg·kg-1组脾脏CD4+和CD8+T淋巴细胞百分率明显升高,ST300和3000μg·kg-1组胸腺和脾脏CD4+和CD8+T淋巴细胞百分率无明显变化。在ST3～3000μg·kg-1内,胸腺和脾脏细胞中Foxp3+调节性T淋巴细胞百分率、胸腺和脾脏组织内Foxp3+调节性T淋巴细胞数量、Foxp3蛋白和mRNA表达均随ST浓度的增高而增加。结论ST可诱导小鼠淋巴器官内Foxp3+调节性T淋巴细胞数量增加,从而影响机体免疫耐受功能。     

胸腺五肽对肺结核合并糖尿病免疫状态影响的研究

目的探讨胸腺五肽联合抗结核药物治疗糖尿病合并肺结核患者对外周血中T淋巴细胞亚群(CD+4、CD+8及其比值)的影响及其临床意义。方法对60例肺结核合并糖尿病的患者,在应用抗结核药物治疗的同时,加用胸腺五肽调节机体免疫力治疗,观察T淋巴细胞亚群(CD+4、CD+8及其比值)的变化,并以60例未应用胸腺五肽的肺结核合并糖尿病患者为对照组。结果经胸腺五肽治疗1、2个月后,患者外周血中T淋巴细胞亚群中CD+4明显升高、CD+8降低,CD+4/CD+8比值升高(P<0.01)。结论胸腺五肽可显著提高肺结核合并糖尿病患者的细胞免疫功能。     

特发性血小板减少性紫癜患者外周血T淋巴细胞亚群变化及临床意义

目的探讨应用流式细胞检测技术测定特发性血小板减少性紫癜患者外周血中血小板相关免疫球蛋白水平及T淋巴细胞亚群变化情况。方法采用流式细胞仪检测我院25例特发性血小板减少性紫癜患者(观察组),对照组(正常健康者)25例,对两组患者外周血中血小板相关免疫球蛋白水平及T淋巴细胞亚群变化比较分析。结果观察组患者外周血中血小板相关免疫球蛋白水平均明显高于对照组(P0.05);观察组患者的CD3+,CD3+CD4+亚群明显较对照组降低(P0.05),而其CD3+CD8+亚群明显较对照组升高(P0.05),且CD3+CD4+/CD3+CD8+比值显著降低(P0.05)。结论特发性血小板减少性紫癜患者外周血中血小板相关免疫球蛋白水平明显增高,T淋巴细胞亚群变化明显,与该病免疫机制有关。     

传染性单核细胞增多症患者T细胞亚群检测分析

目的应用流式细胞术检测传染性单核细胞增多症(IM)患者与正常儿童T淋巴细胞及其亚群的百分比;比较IMEB病毒(EBV)阳性组与IMEBV阴性组患者T淋巴细胞及其亚群的百分比的变化,探讨IM患者急性期免疫功能状态。方法选取资料完整的IM患者39例,同期正常儿童40例作为对照,比较两组患者外周血T淋巴细胞亚群CD4+细胞、CD8+细胞及CD4+/CD8+的变化。另IM组39例分为EBV阳性组32例,IMEBV阴性组7例,比较两组患者T淋巴细胞亚群CD4+细胞、CD8+细胞及CD4+/CD8+的变化。结果IM组患者与对照组相比CD4+细胞百分比明显下降,CD8+细胞百分比明显升高,CD4+/CD8+明显下降。IMEBV阳性组与IMEBV阴性组比较,CD4+细胞百分比明显下降,CD8+细胞百分比明显升高,CD4+/CD8+明显下降。结论传染性单核细胞增多症患者存在免疫功能紊乱,其免疫功能的紊乱程度与EB病毒感染有关。     

支原体肺炎儿童外周血CD4+CD25+调节性T细胞水平的变化及维生素A的调节作用

目的 探讨肺炎支原体肺炎(MPP)患儿外周血淋巴细胞中CD4+ CD25+调节性T细胞(Treg)、T细胞亚群CD3+、CD4+、CD4+/CDs水平的变化及临床意义;探讨体外实验时维生素A体内活性代谢产物视黄酸对MPP患儿外周血淋巴细胞CD4+ CD25+ Treg细胞、T细胞亚群CD3+、CD4+表达及CD4+/CD8+比率的调节干预作用.方法 选择2012年10-12月在空军总医院儿科确诊为MPP的20例住院患儿作为研究对象,其中10例患儿作为病例试验组,另10例患儿作为病例对照组(即未与视黄酸孵育),同期10例同龄健康儿童作为正常对照组.收集患儿及正常对照儿童外周血标本,分离单个核细胞,用流式细胞仪检测外周血淋巴细胞中CD4+ CD25+ Treg细胞、T细胞亚群CD3+、CD4+、CD4+/CD8+水平,病例试验组提取其淋巴细胞在体外培养基中加入一定量视黄酸共同培养孵育,再次测定CD4+ CD25+ Treg细胞、T细胞亚群CD3+、CD4+、CD4+/CD8+水平,将上述指标进行比较分析.结果 病例组患儿外周血淋巴细胞中CD4+ CD25+ Treg细胞、CD4+/CD8+、CD3+百分比分别为(4.5±1.9)％、(1.3±0.9)％、(38.9±11.4)％,正常对照组儿童分别为(13.2±2.5)％、(7.9±3.0)％、(65.1±8.8)％,病例对照组明显低于正常对照组,差异有统计学意义(P＜0.05),而与视黄酸共同孵育后病例试验组以上指标明显升高,分别上升至(9.2±3.8)％、(5.9±2.5)％、(81.3±11.6)％,与病例对照组比较差异有统计学意义(P＜0.05),与正常对照组比较差异无统计学意义(P＞0.05).结论 MPP患儿外周血淋巴细胞中CD4+ CD25+ Treg细胞、CD3+T细胞表达明显受抑,CD4+/CD8+亚群比例异常,T细胞亚群数量及功能明显紊乱,而体外试验时维生素A体内活性代谢产物视黄酸干预后能增强淋巴细胞CD4+ CD25+ Treg细胞、CD3+ T细胞表达,恢复CD4+/CD8+亚群比例,纠正T细胞亚群功能失衡,从而增强、协调机体免疫、抗感染能力,为维生素A辅助治疗MPP提高参考.     

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.     

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.