氯通道阻断剂对T淋巴细胞增殖的影响

目的探讨氯通道开放在Ｔ淋巴细胞增殖过程中的作用。方法新鲜分离成人外周血Ｔ淋巴细胞,以ＣｏｎＡ诱导其增殖,用［３Ｈ］ ＴｄＲ参入法测定并比较氯通道阻断剂ＤＩＤＳ、ＮＰＰＢ、９ ＡＣ、ＮＦＡ、Ｆｕｒｏｓｅｍｉｄｅ对Ｔ淋巴细胞增殖的作用;测定钙通道阻滞剂ＳＫ＆Ｆ９６３６５、硝苯吡啶以及免疫抑制剂环孢霉素Ａ（ＣｓＡ）对Ｔ淋巴细胞增殖的作用;比较ＤＩＤＳ、ＮＰＰＢ与ＳＫ＆Ｆ９６３６５或ＣｓＡ的相互作用。结果９ ＡＣ,ＮＦＡ,Ｆｕｒｏｓｅｍｉｄｅ对Ｔ细胞增殖无明显抑制作用;ＤＩＤＳ、ＮＰＰＢ呈浓度依赖性地抑制Ｔ细胞增殖,ＩＣ５０分别为１６８２３±３３６和（１２４３５±４２４）μｍｏｌ·Ｌ－１,并显著增强ＳＫ＆Ｆ９６３６５及ＣｓＡ抑制Ｔ细胞增殖的作用,且ＮＰＰＢ增强抑制作用强于ＤＩＤＳ。结论阻断氯通道可抑制ＣｏｎＡ诱导的Ｔ淋巴细胞增殖活化,氯通道开放影响细胞钙运动。     

环孢菌素A人体药代动力学研究进展

环孢菌素Ａ(ｃｙｃｌｏｓｐｏｒｉｎＡ ,ＣｓＡ)是一种高效免疫抑制剂 ,具有亲脂性环状多肽结构 ,含 11个氨基酸。该药于 1971年从Ｔｏｌｙｐｏｃｌａｄｉｕｍｉｎｆｌａｔｕｍ ｇａｍｓ真菌中分离出来 ,1978年首次用于临床 ,现广泛用于器官移植、骨髓移植患者及自身免疫性疾病的治疗。ＣｓＡ可选择性地抑制Ｔ辅助淋巴细胞及免疫反应 ,诱导早期的Ｔ细胞依赖性抗体的产生 ;也能抑制淋巴激活素包括白细胞介素Ⅱ和Ｔ细胞生长因子的产生和释放 ;抑制Ｔ诱导细胞 ,减少巨噬细胞产生白细胞介素Ⅰ。ＣｓＡ主要作用于淋巴细胞增殖早期 ,抑制作用是可…     

绞股蓝总皂苷对内毒素、氧自由基介导血管内皮细胞表达c-sis基因和调节平滑肌细胞增殖的影响

目的　研究绞股蓝总皂苷（ Ｇｙｐ） 对血管平滑肌细胞增殖的调节与内皮细胞ｃ ｓｉｓ 基因表达和一氧化氮（ Ｎ Ｏ） 合成／ 释放的关系。方法　采用原位杂交法检测内皮细胞ｃ ｓｉｓｍ Ｒ Ｎ Ａ 表达,用 Ｇｒｉｅｓｓ 法测定内皮细胞 Ｎ Ｏ 释放量,用 Ｍ Ｔ Ｔ快速比色法检测平滑肌细胞（ Ｓ Ｍ Ｃ） 增殖。结果　内毒素（ Ｌ Ｐ Ｓ）１６ ｍｇ· Ｌ－ １ 促进牛主动脉内皮细胞ｃ ｓｉｓ 基因表达,明显降低内皮细胞培养液中一氧化氮含量,刺激 Ｓ Ｍ Ｃ 增殖;黄嘌呤－ 黄嘌呤氧化酶（ Ｘ Ｘ Ｏ） 系统产生的氧自由基（ Ｏ Ｆ Ｒ） 具有与 Ｌ Ｐ Ｓ 相似的作用。绞股蓝总皂苷对 Ｌ Ｐ Ｓ诱导的内皮细胞ｃ ｓｉｓ 基因表达具有明显抑制作用,并能对抗 Ｏ Ｆ Ｒ 诱导的 Ｅ Ｃ 损伤,保护内皮细胞释放 Ｎ Ｏ 的能力,抑制 Ｌ Ｐ Ｓ 和 Ｏ Ｆ Ｒ通过 Ｅ Ｃ 介导的 Ｓ Ｍ Ｃ 增殖。 Ｇｙｐ 的效应可被 Ｎ Ｏ 合成酶抑制剂硝基 左旋精氨酸部分取消。结论　绞股蓝总皂苷通过抑制内皮细胞ｃ ｓｉｓ 基因表达,促进内皮细胞合成（ 释放） Ｎ Ｏ抑制平滑肌细胞增殖     

环孢素A对正常红细胞免疫功能的抑制作用

环孢素Ａ（Ｃｉｃｌｏｓｐｏｒｉｎ Ａ， ＣｓＡ）作为一种强力免疫抑制剂，已广泛用于各种器官移植及自身免疫性疾病的治疗，它的主要作用是阻断Ｇ０或Ｇ１早期的休止淋巴细胞，并通过激活的Ｔ淋巴细胞来抑制抗原触发的淋巴因子的产生与释放，从而抑制整个机体的免疫反应系统。但其对红细胞免疫功能抑制作用的研究尚未见报道，以红细胞Ｃ３ｂ受体花环作为红细胞免疫功能指标，通过体外实验证实了一定浓度的环孢素对红细胞免疫功能有明显的抑制作用。１　材料与方法１．１　材料：正常人红细胞标本（献血员新鲜红细胞）；红细胞Ｃ３ｂ受体花…     

IL-2-PE40对免疫活性T细胞的影响

目的研究ＩＬ－２－ＰＥ４０对免疫活性Ｔ细胞的影响。方法采用ＣｏｎＡ刺激的淋巴细胞增殖试验、混合淋巴细胞培养（ＭＬＣ）及细胞毒试验。结果ＩＬ－２－ＰＥ４０对ＣｏｎＡ诱导的小鼠脾细胞有十分强的细胞毒性，能选择性地抑制ＭＬＣ中抗原活化的Ｔ细胞活性，保留未活化Ｔ细胞对ＣｏｎＡ诱导的丝裂原反应，在培养ｄ３加入ＩＬ－２－ＰＥ４０比培养开始时加入对ＭＬＣ抑制作用强。结论ＩＬ－２－ＰＥ４０能够高度选择性抑制免疫活性Ｔ细胞，是ＩＬ－２Ｒ靶向治疗中具有潜力的一种免疫抑制剂。     

盐藻β—胡萝卜素的免疫药理研究：II对T淋巴细胞增殖及T淋巴细胞亚…

采用植物血凝素（ＰＨＡ）诱导Ｔ淋巴细胞转化率和单克隆抗体间接免疫荧光技术，分析了盐藻β－胡萝卜素（β－Ｃ）对Ｔ淋巴细胞的增殖及Ｔ淋巴细胞亚群的作用，结果表明，β－Ｃ对ＰＨＡ诱导的Ｔ淋巴细胞增殖有明显促进作用，对环磷酰胺（ＣＴＸ）抑制的Ｔ淋巴细胞转化率能明显升高；β－Ｃ能明显提高正常小鼠和免疫能力低下小鼠Ｌ３Ｔ４细胞的百分率，使Ｌ３Ｔ４／Ｌｙｔ－２的比值升高，大剂量可对抗ＣＴＸ的作用，降低Ｌｙｔ－２     

免疫抑制剂子囊霉素及其衍生物

子囊霉素（ａｓｃｏｍｙｃｉｎ）为２３碳的大环内酯类结构， ３０多年前从含有吸水链霉菌（ＫＫ３１７）的土壤中 分得。以往只知道它具有抗真菌和抗生素活性；直到１９８７年发现了类似物他克莫司（ｔａｃｒｏｌｉｍｕｓ，ＦＫ５０６，１），才推动了对子囊霉素性质和生物活性的认识。Ｆｕjｉｓａｗａ及Ａｂｂｏｔｔ公司从吸水链霉菌变种的发酵液中发现了ＦＲ·９００５２０和ＡＴＣＣ１４８９１，它们在光谱、色谱、化学结构上与子囊霉素相同，也类似于化学性质不同的环孢素Ａ（２）。子囊霉素及其类似物结合到细胞内结合蛋白亲免素（ｉm…     

Fas与HIV感染

Ｆａｓ抗原（Ｆａｓ Ａｇ）表达与人类免疫缺陷症病毒（ＨＩＶ）感染引起的艾滋病（ＡＩＤＳ）进程有密切关系。随着ＨＩＶ感染的加重，细胞表面Ｆａｓ Ａｇ表达增加，主要表现在ＣＤ４＾＋和ＣＤ８＾＋细胞。通过Ｆａｓ Ａｇ介导的细胞程序死亡（ＰＣＤ）途径是ＨＩＶ感染引起的Ｔ淋巴细胞免疫缺陷的重要原因，白细胞介素２（ＩＬ－２），ＩＬ－１２等细胞因子以及ＩＬ－１β转化酶（ＩＣＥ）样蛋白酶抑制剂在体外能抑制由Ｆａｓ     

牛膝多糖对T淋巴细胞和天然杀伤细胞功能的影响

牛膝多糖（ＡＢＰ）是从中药牛膝根中分离得到的一种有效成分。ＡＢＰ５０－８００ｍｇ·Ｌ－１在体外增强天然杀伤（ＮＫ）细胞活性和促进伴刀豆球蛋白Ａ（ＣｏｎＡ）诱导的肿瘤坏死因子－β（ＴＮＦ－β）产生；但不能提高ＣｏｎＡ诱导的Ｔ淋已细胞增殖反应和白介素２的产生．ＡＢＰ５０及１００ｍｇ·ｋｇ－１ｉｐ明显提高正常小鼠ＮＫ细胞活性和ＴＮＦ─β生成，增强二硝基氟苯诱导的迟发型超敏反应和对抗环磷酰胺对ＮＫ活性的抑制作用。但对ＣｏｎＡ诱导的Ｔ淋巴细胞增殖反应和白介素２的产生无明显影响。表明ＡＢＰ对Ｔ淋巴细胞功能的影响是有选择性的．ＡＢＰ对ＮＫ细胞的杀伤活性的增强作用是明显的．     

环孢素A人体药动学影响因素分析

环孢素Ａ(ｃｙｃｌｏｓｐｏｒｉｎＡ ,ＣｓＡ)是一种高效免疫抑制剂 ,具有亲脂性的环状多肽结构 ,含 11个氨基酸。该药于 1971年从真菌Ｔｏｌｙｐｏｃｌａｄｉｕｍｉｎｆｌａｔｕｍ中分离出来 ,1978年首次用于临床 ,现广泛用于肾脏、肝脏、心脏、骨髓移植患者及自身免疫性疾病的治疗。ＣｓＡ可选择性地抑制Ｔ辅助淋巴细胞及免疫反应 ,主要作用于淋巴细胞增殖早期 ,抑制作用是可逆的。ＣｓＡ不抑制造血系统 ,也不直接作用于巨噬细胞 ,因而不引起白细胞和血小板减少。ＣｓＡ的主要不良反应为与剂量有关的肾毒性、肝毒性等。由于ＣｓＡ的生物利…     

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.

     

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.     

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.     

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.