康乐霉素C对T—和B—淋巴细胞活化的抑制作用

目的：阐明康乐霉素Ｃ对脾细胞增殖和Ｔ－细胞亚型的作用。方法：氚掺入法或噻唑蓝比色法测定细胞增殖；用荧光激活细胞分选仪测定细胞亚群；曲利苯蓝排斥法测定细胞存活率。结果：Ｋａｎ８，４０，８０和４００ｎｍｏｌ．Ｌ＾－１除抑制丝 同种异型抗原刺激的小鼠脾细胞增殖外；与Ｃｉｃ不同，抑制ＬＰＳ刺激的脾细胞增殖；使Ｌ３Ｔ４＾｜Ｌ－细胞亚型比倒置；     

Effect of 3,6-dimethamidodibenzopyriodonium citrate on Ca~(2 ) in rabbit platelet in vitro

目的：观察Ｉ６５对家兔血小板胞浆游离钙离子（［Ｃａ２＋］ｉ）浓度的影响．方法：用Ｑｕｉｎ２ＡＭ荧光探针在体外测定家兔血小板［Ｃａ２＋］ｉ．结果：ＣａＣｌ２１ｍｍｏｌ·Ｌ－１时，Ｉ６５（１０，２０和３０μｍｏｌ·Ｌ－１）使血小板［Ｃａ２＋］ｉ分别由１４２±２２ｎｍｏｌ·Ｌ－１和１２４±１８ｎｍｏｌ·Ｌ－１减少到１１８±２０，７８±１２，４０±１０ｎｍｏｌ·Ｌ－１和１０８±１５，７７±１４，３７±１４ｎｍｏｌ·Ｌ－１．用依他酸２ｍｍｏｌ·Ｌ－１络合胞外Ｃａ２＋，Ｉ６５胞内贮存Ｃａ２＋释放从５２±１１ｎｍｏｌ·Ｌ－１减少至３４±９，１９±６和１１±５ｎｍｏｌ·Ｌ－１．另外，Ｉ６５也使胞外Ｃａ２＋跨膜内流从９１±１３ｎｍｏｌ·Ｌ－１分别降至８４±１５，５８±１５和２８±１９ｎｍｏｌ·Ｌ－１．结论：Ｉ６５不仅明显抑制家兔血小板胞外Ｃａ２＋跨膜内流而且抑制胞内贮存Ｃａ２＋释放．     

Kanglemycin C vs ciclosporin on immunosuppression in mice

目的：与环孢素（Ｃｉｃ）比较,研究康乐霉素Ｃ（Ｋａｎ）对小鼠免疫系统的影响．方法：皮肤迟发性超敏反应（ＤＨ）和环磷酰胺（Ｃｙｃ）增强型ＤＨ;同种异型皮肤和心脏移植;脾细胞溶血素测定;腹腔巨噬细胞吞噬中性红．结果：Ｋａｎ（１２５,２５,５０ｍｇ·ｋｇ－１·ｄ－１,ｉｇ,８ｄ）与Ｃｉｃ相似,抑制小鼠皮肤ＤＨ和Ｃｙｃ增强型ＤＨ（Ｐ＜００１）;延长小鼠同种异型皮肤和心脏移植物存活时间（Ｐ＜００１）;对溶血素产生也有抑制作用（Ｐ＜００１）;Ｋａｎ５０ｍｇ·ｋｇ－１·ｄ－１,ｉｇ,５ｄ与Ｃｙｃ相似,对小鼠腹腔巨噬细胞吞噬中性红无明显作用（Ｐ＞００５）．结论：Ｋａｎ显著抑制小鼠细胞免疫和体液免疫,但不影响巨噬细胞的吞噬．     

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．     

氯苯扎利钠对小鼠T淋巴细胞及其亚型的影响

本文报道了氯苯扎利钠（ＣＣＡ）对小鼠淋巴细胞转化及对迟发性超敏反应（ＤＴＨ）的影响。结果表明，ＣＣＡ２５，５０，１００ｍｇ·ｋｇ－１·ｄ－１ｉｇ，５一８ｄ对环磷酰胺（Ｃｙ，２５０和８０ｍｇ·ｋｇ－１）诱导的小鼠ＤＴＨ反应增高或降低呈双向调节作用。ＣＣＡ对由伴刀豆球蛋白Ａ。脂多糖诱导的小鼠脾淋巴细胞增殖反应有增强作用。进而通过单克隆抗体间接免疫荧光法证明ＣＣＡ（５０，１００ｍｇ·Ｌ－１）使小鼠Ｌｙｔ－２＋细胞数增多，降低Ｌ３Ｔ４＋／Ｌｙｔ一２＋比值。     

钙拮抗剂TMB-8抑制BHQ,NE和KCl引起的培养乳牛基底动脉单个平滑肌细胞内游离钙的升高

用ＡＲＣＭＭＩＣ阳离子测定系统，测量单个细胞内游离钙浓度（［Ｃａ２＋］ｉ），研究８（Ｎ，Ｎ二乙胺）ｎ辛基３，４，５三甲氧基苯甲酸酯（ＴＭＢ８）对培养乳牛基底动脉平滑肌［Ｃａ２＋］ｉ的作用。在细胞外钙浓度为１３ｍｍｏｌ·Ｌ－１时，ＴＭＢ８（３０μｍｏｌ·Ｌ－１）可明显抑制ＢＨＱ，ＮＥ及ＫＣｌ引起［Ｃａ２＋］ｉ的升高。在细胞外钙为零＋ＥＧＴＡ０１ｍｍｏｌ·Ｌ－１时，ＴＭＢ８（１０，３０及１００μｍｏｌ·Ｌ－１）可浓度依赖性地降低静息［Ｃａ２＋］ｉ，ＴＭＢ８（３０μｍｏｌ·Ｌ－１）可几乎完全阻断ＢＨＱ及ＮＥ引起［Ｃａ２＋］ｉ的增加。研究表明ＴＭＢ８降低培养乳牛基底动脉平滑肌［Ｃａ２＋］ｉ的机制，主要是抑制肌浆网Ｃａ２＋的释放，或增加肌浆网对Ｃａ２＋的摄入，并由此间接地抑制细胞外钙的内流。     

10－羟基－2－癸烯酸对小鼠T淋巴细胞及其亚型和白介素2产生的影响

观察了１０－羟基－２－癸烯酸（１０－ＨＤＡ）对小鼠Ｔ淋巴细胞及其亚型和白介素２产生的影响．结果表明，１０－ＨＤＡ１，５，２５ｍｇ·ｋｇ－１·ｄ－１ｉｐ，５ｄ可拮抗环磷酰胺１００ｍｇ·ｋｇ－１对小鼠迟发型超敏反应（ＤＴＨ）的抑制作用．体外给药，１０－ＨＤＡ可促进刀豆球蛋白Ａ诱导的Ｔ淋巴细胞增殖反应；促进小鼠脾细胞产生白介素２．采用单克隆抗体间接免疫荧光法证明１０－ＨＤＡ可增加小鼠胸腺Ｌ３Ｔ＋４细胞数，而对Ｌｙｔ－２＋细胞无明显影响．结果提示１０－ＨＤＡ可调节Ｔ淋巴细胞参与的免疫反应．     

白芍总甙对佐剂性关节炎大鼠滑膜细胞功能和脾细胞增殖反应的影响

本文研究了白芍总甙（ＴＧＰ）对大鼠佐剂性关节炎（ＡＡ）滑膜细胞功能以及脾淋已细胞增殖反应的影响及其作用机理。结果表明，ＴＧＰ５０ｍｇ·ｋｇ－１·ｄ－１×１０ｄｉｇ可使ＡＡ大鼠滑膜细胞过度分泌白介素１，肿癌坏死因子（ＴＮＦ）和前列腺素Ｅ２（ＰＧＥ２）的功能恢复正常，继而下调滑膜成纤维细胞的增殖；吲哚美辛２ｍｇ·ｋｇ－１·ｄ－１×１０ｄｉｇ抑制ＰＧＥ２产生，但增加ＡＡ大鼠滑膜细胞分泌白介素１与ＴＮＦ，从而促进滑膜成纤维细胞的增殖。ＴＧＰ５０ｍｇ·ｋｇ－１·ｄ－１×１０ｄｉｇ恢复ＡＡ大鼠脾细胞过低的伴刀豆球蛋白Ａ（ＣｏｎＡ）增殖反应与其下调巨噬细胞产生一氧化氮和ＰＧＥ２有关；体外实验亦证明，高浓度（０．４——６．４ｍｇ·Ｌ－１）ＴＧＰ负调节脾细胞ＣｏｎＡ增殖反应与其促进巨噬细胞产生一氧化氮和ＰＧＥ２有关。     

粉防己碱和蝙蝠葛碱对人白血病细胞株HL－60和K_（562）的生长抑制作用

研究粉防己碱（Ｔｅｔ）和蝙蝠葛碱（Ｄａｎ）对人早幼粒细胞白血病ＨＬ－６０和人红白细胞白血病Ｋ５６２增长的影响，并与维拉帕米（Ｖｅｒ）和三氟拉嗪（ＴＦＰ）比较。结果Ｔｅｔ和Ｄａｕ对ＨＬ－６０和Ｋ５６２的增长有很强抑制作用，呈浓度依赖性，ＩＣ５０分别为３．０，４．４ｍｇ·Ｌ－１和３．３，５．６ｍｇ·Ｌ－１；Ｔｅｔ还抑制ＨＬ－６０细胞的分裂相。同样条件下Ｖｅｒ和ＴＦＰ对ＨＬ－６０和Ｋ５６２也有抑制作用，但较前两者为弱。Ｔｅｔ和Ｄａｎ为双苄基异喹啉生物碱，已被阐明有Ｃａ２＋拮抗剂和ＣａＭ抑制剂活性，提示其抑制肿瘤细胞生长与此有关，并有可能代替常用的Ｃａ２＋拮抗剂Ｖｅｒ与化疗药联合应用于肿瘤的治疗。     

白芍总甙对大鼠腹腔巨噬细胞产生前列腺素E_2的作用及部分机制研究

白芍总甙（ＴＧＰ，０．０１～１００ｍｇ·Ｌ－１）对亚适浓度Ａ２３１８７（０．１μｍｏｌ·Ｌ－１）激活的大鼠腹腔巨噬细胞（ＰＭΦ）产生的前列腺素Ｅ２（ＰＧＥ２）呈现低浓度促进和高浓度抑制的双向调节作用。而ＴＧＰ对最适浓度Ａ２３１８７（１μｍｏｌ·Ｌ－１）激活的ＰＭΦ产生的ＰＧＥ２呈浓度依赖性的抑制作用，其ＩＣ５０为１６．７ｍｇ·Ｌ－１。在整体模型上，ＴＧＰ（５０ｍｇ·ｋｇ－１×１０ｄ）能使佐剂性关节炎（ＡＡ）大鼠ＰＭΦ产生过高的ＰＧＥ２恢复正常水平。采用Ｆｕｒａ－２／ＡＭ荧光法测定ＴＧＰ对Ａ２３１８７（１μｍｏｌ·Ｌ－１）诱导正常大鼠ＰＭΦ胞内游离钙离子浓度［Ｃａ２＋］ｉ，发现ＴＧＰ（≤１０ｍｇ·Ｌ－１）对ＰＭΦ［Ｃａ２＋］ｉ无明显影响，而ＴＧＰ在（１０～１００ｍｇ·Ｌ－１）时，对ＰＭΦ［Ｃａ２＋］ｉ有一定抑制作用。提示高浓度ＴＧＰ对ＰＧＥ２的负向调节作用可能与抑制细胞内钙有关。     

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.     

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.