白细胞介素2及其受体单克隆抗体的应用

白细胞介素２（ＩＬ－２）有其受体（ＩＬ－２Ｒ）在机体免疫应答中起重要作用，抗ＩＬ－２单克隆抗体（ＭｃＡｂ）及抗ＩＬ－２ＲＭｃＡｂ已在实验室及临床研究中得到广泛应用，利用抗ＩＬ－２ＭｃＡｂ作亲和层析提纯ＩＬ－２操作简便，纯度高且保持较高的生物学活性；酶免疫法测定了ＩＬ－２敏感度高，稳定性强，而且有希望试制成试剂盒，抗ＩＬ－２ＭｃＡｂ还可用于移植物排斥反应的监测及一些疾病的治疗。抗ＩＬ－２ＲＭｃＡｂ是     

关注雷公藤制剂的用药安全

近期,国家食品药品监督管理局(SFDA)发布了雷公藤制剂引起的安全性问题。雷公藤是常用中药,是卫矛科雷公藤属植物雷公藤Tripterygium wilfordii Hook.f.的根,具有祛风除湿、活血通络、消肿止痛的功效,临床用于类风湿性关节炎等免疫系统疾病。雷公藤制剂作为疗效确切的免疫抑制剂广泛用于临床,如类风湿性关节炎、肾病综合征等。已上市的雷公藤制剂包括:雷公藤多     

43例支气管哮喘患儿T淋巴细胞及亚群的测定

采用人Ｔ细胞单克隆抗体（ＭＣＡｂ）间接荧光法,用ＭＣＡｂ及ＦＩＦＣ标记羊抗鼠ＩｇＧ抗体测定４３例３个月至１２岁哮喘患儿及同年龄组的２９例健康儿,分别检测外周静脉血ＣＤ３＋、ＣＤ４＋、ＣＤ８＋及Ｂ细胞的百分率,ＣＤ４＋／ＣＤ８＋的细胞比值。结果显示,哮喘患儿的发病可能主要与免疫紊乱有关。     

43例支气管哮喘患儿TI林巴细胞及亚群的测定

采用人Ｔ细胞单克隆抗体（ＣＭＡｂ）间接荧光法，用ＭＣＡｂ及ＦＩＦＣ标记羊抗鼠ＩｇＧ抗体测定４３例３个月至１２岁哮喘患儿及年龄组的２９例健康儿，分别检测外周静脉血ＣＤ３、ＣＤ４、ＣＤ８及Ｂ细胞的百分率，ＣＤ４／ＣＤ８的细胞比值。结果显示，哮喘患儿的发病可能主要与免疫紊乱无关。     

抗人CD3单抗在体外诱导LAK和TIL增殖的实验研究

目的 观察抗人ＣＤ３单抗（ａＣＤ３ＭｃＡｂ）对单核细胞（ＰＢＭＣ）和肿瘤组织中提取的浸润淋巴细胞（ＴＩＬ）增殖的影响。方法 将外周血中分离出的ＰＢＭＣ和ＴＩＬ进行扩增培养,同时测定其活性。结果 ａＣＤ３ＭｃＡｂ和白细胞介素－２（ＩＬ－２）的浓度是包被法制备ＣＤ３单克隆抗体激活的杀伤细胞（ＣＤ３ＡＫ）的主要影响因素。经选择ａＣＤ３ＭｃＡｂ的最适蛋白浓度为０．１ｕｇ／ｍｌ,ＩＬ－２为２０Ｕ／ｍｌ。结论     

IL-2基因转移对CD3AK细胞生物学功能的影响研究

白细胞介素 2 (ＩＬ 2 )是Ｔ细胞活化分泌 ,能与Ｔ细胞上ＩＬ 2Ｒ结合后 ,增强Ｔ细胞增殖的一种重要的细胞因子。ＣＤ3ＡＫ细胞是利用抗ＣＤ3单克隆抗体与ＴＣＲ/ＣＤ3 复合体的结合 ,同时提供少量外源ＩＬ 2 ,激活产生的具有细胞毒效应的杀伤细胞 ,常用于过继免疫治疗。临床资料表明体内使用外源性ＩＬ 2常导致毒副作用。能否利用基因转移技术将ＩＬ 2基因导入ＣＤ3ＡＫ细胞 ,使其表达并维持ＣＤ3ＡＫ的活化状态呢 ?抗ＣＤ3ＭｃＡｂ活化的Ｔ细胞作为逆转录病毒载体的受体细胞 ,已有应用于ＩＬ 1 β基因转移研究的报道。本实验利用逆转录病…     

雷藤氯内酯醇对正常人及类风湿关节炎患者周围血单个核细胞及滑膜细胞产生免疫球蛋白的影响

研究了１０例正常人和６例类风湿关节炎（ＲＡ）患者外周血单个核细胞（ＰＢＭＣ）及３例ＲＡ患者消化的单个滑膜细胞（ＤＳＳＣ），经雷公藤的有效单体雷藤氯内酯醇（Ｔ４）处理２ｈ对其分泌免疫球蛋白（Ｉｇ）的影响。结果显示：Ｔ４在浓度为５～３５ｎｇ·ｍｌ－１对正常人ＰＢＭＣ分泌Ｉｇ有明显抑制作用，呈剂量依赖趋势。在２５ｎｇ·ｍｌ－１浓度下，Ｔ４对ＲＡ患者ＰＢＭＣ及ＤＳＳＣ分泌Ｉｇ均有明显抑制作用。     

粉防己碱逆转肿瘤多药抗药性细胞的凋亡抗性作用

目的探讨粉防己碱逆转ＭＤＲ细胞凋亡抗性的作用及其机制。方法ＭＤＲ细胞株ＭＣＦ－７／Ａｄｒ与其相应的敏感株ＭＣＦ－７进行对比研究。比较粉防己碱对阿霉素（Ｄｏｘ）诱导ＭＤＲ细胞及其相应的敏感株的凋亡作用。并比较粉防己碱对ＭＤＲ细胞及其相应的敏感株的细胞ｂｃｌ－２蛋白的表达的影响。细胞凋亡及ｂｃｌ－２蛋白表达的测定以流式细胞仪法。结果加入Ｄｏｘ共同培养２４ｈ可诱导７４．６％ＭＣＦ－７细胞凋亡，而只引起１４．３％的ＭＣＦ－７／Ａｄｒ细胞凋亡。只加入粉防己碱共同培养２４ｈ，未见明显增加ＭＤＲ细胞及其相应敏感细胞的凋亡百分比。Ｄｏｘ＋粉防己碱能显著地使ＭＤＲ细胞的凋亡增至４７．０％，与单独用Ｄｏｘ组相比较，差异有显著性（Ｐ＜０．０１），而敏感细胞株为７７．８％，与单独用Ｄｏｘ组相比较，差异无显著性（Ｐ＞０．０５）。ＭＤＲ细胞株与其相应的敏感株ｂｃｌ－２蛋白表达水平均较低且差异无显著性。加入粉防己碱对ＭＤＲ细胞株与其相应的敏感株ｂｃｌ－２蛋白表达水平均未见明显影响。结论粉防己碱能逆转ＭＤＲ细胞对Ｄｏｘ的凋亡抗性。其逆转机制可能与ｂｃｌ－２蛋白表达无关。粉防己碱逆转ＭＤＲ细胞ＭＣＲ－７／ＡＤＲ对Ｄｏｘ的凋亡抗性的机制有待进?     

IDDM病人发病不同时期血清自身免疫抗体水平观察

胰岛素依赖性糖尿病 (ＩＤＤＭ)是与ＨＬＡ ＤＲ、ＨＬＡ Ｂ等人类组织相容性抗原相关的慢性自身免疫性疾病。病人体内可产生谷氨酸脱羧酶抗体 (ＧＡＤ Ａｂ)、胰岛细胞抗体(ＩＣＡ)、胰岛素抗体 (ＩＡＡ)等自身免疫抗体。近年来国内外有关运用体内自身免疫抗体ＧＡＤ Ａｂ、ＩＣＡ、ＩＡＡ检测作为ＩＤＤＭ鉴定、预防指标的报道较多 ,但关于体内自身免疫抗体在发病后的动态水平报道较少。我科对门诊及住院ＩＤ ＤＭ病人发病不同时期血清ＧＡＤ Ａｂ、ＩＣＡ进行测定 ,了解抗体水平变化。1　材料与方法1 1　仪器　带有 40 5ｎｍ波长光源的酶…     

甲砜霉素甘氨酸酯盐酸盐的合成

甲砜霉素甘氨酸酯盐酸盐的合成ＳＹＮＴＨＥＳＩＳＯＦＴＨＩＡＭＰＨＥＮＩＣＯＬＧＬＹＣＩＮＡＴＥＨＹＤＲＯＣＨＬＯＲＩＤＥ朱平（浙江省医药发展公司，杭州３１０００６）ＺＨＵＰｉｎｇ（ＴｈｅＭｅｄｉｃｉｎｅＤｅｖｅｌｏｐｉｎｇＣｏｒｐ．ｏｆＺｈｅｊｉａｎ...     

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.