胸腺五肽的波谱学解析与结构表征

目的为多肽类化合物的NMR解析提供理论基础和方法学依据。方法利用NMR、2D NMR及IR、UV、MS并借助1H-1H COSY1、3C-1H COSY及DEPT实验技术详细研究了胸腺五肽的结构特征。结果对胸腺五肽的氢谱和碳谱进行了完全归属。结论胸腺五肽的结构得到确认并为多肽类药物的结构解析提供了有益的分析依据。     

固相合成胸腺五肽的分离纯化与鉴定

目的 建立胸腺五肽分离纯化、分析鉴定方法,有效提高胸腺五肽含量。方法 将标准Fmoc方法固相合成的胸腺五肽以Sephadex G-25凝胶柱使粗肽脱盐,以循环制备液相色谱仪进行粗肽纯化,以质谱法进行分子质量的鉴定。结果 该法得到胸腺五肽的纯度为99.02% ,分子质量测定值与理论值相符。结论 建立了高效,简便的胸腺五肽分离纯化方法, 为工业化生产提供了实验依据。     

胸腺五肽研究进展

胸腺五肽具人工合成的五肽，其氨基酸顺序和结构与胸腺生成素的３２－３６位氨基酸组成相同，是ＴＰ重要的功能活性部分，具有与ＴＰ相似的生物活性。动物实验和临床研究证明了ＴＰ５对免疫功能低下和自身免疫病患者的免疫功能具有重要的调节作用。     

胸腺五肽一级结构的电喷雾质谱分析

目的测定胸腺五肽的相对分子质量及其一级结构。方法应用电喷雾质谱法(ESIMS)及源内碰撞诱导解离技术对胸腺五肽进行测定,根据其典型碎片离子确证其氨基酸序列及相对分子质量。结果测得胸腺五肽准分子离子峰(M+H)+m/z680.3及(M+Na)+m/z702.2,(M+2Na-H)+m/z724.3及(M+3Na-2H)+m/z746.2,表明胸腺五肽的相对分子质量为679.4,与理论值一致。结论胸腺五肽的相对分子质量及一级结构与理论值相符。     

胸腺五肽溶液稳定性考察

建立了胸腺五肽含量的HPLC检测法，采用C18柱，流动相为50mmo/L磷酸二氢钾溶液（pH7．0）·甲醇（85：15）；流速lml／min；检测波长275nm。考察了胸腺五肽在不同温度、pH、缓冲盐体系中的稳定性。结果表明，胸腺五肽在酸性介质中降解速度加快。磷酸缓冲体系较柠檬酸缓冲体系更有利于保持胸腺五肽的稳定。     

RP-HPLC法测定胸腺五肽溶液的稳定性

目的考察胸腺五肽溶液的稳定性。方法采用RP-HPLC法,分别考察了温度(冷冻、冷藏、37℃、60℃)、缓冲液种类(磷酸盐、三羟甲基氨基甲烷-盐酸、枸橼酸盐、醋酸盐、碳酸盐、硼酸盐)、pH值(2.0~10.0)、光照及超声(200、400、600W)等因素对胸腺五肽溶液稳定性的影响。结果胸腺五肽含量的标准曲线方程为A=1.015×103ρ-1.319×103,r=0.999 8。胸腺五肽在质量浓度5~400mg.L-1内与峰面积呈良好的线性关系,精密度与回收率符合要求。胸腺五肽溶液在冷冻条件下30d内基本稳定;在冷藏条件下7 d内含量保持不变;放置于37℃时,48h内稳定性良好;60℃时,24h后药物开始降解。当溶液的pH值为5.0~9.2时,胸腺五肽溶液在4d内稳定性较好。缓冲液的种类对其稳定性的影响不大。在24h内光照对药物的稳定性基本无影响。以200W功率超声15min,胸腺五肽溶液基本稳定;以400W和600W功率超声时,7min和5min后药物开始降解。结论本实验中所建立的用于胸腺五肽溶液稳定性测定的RP-HPLC法,操作简便,精密度与回收率符合要求,且对降解产物具有很好的分离效果,适用于对胸腺五肽溶液稳定性的评价。     

胸腺五肽治疗重型肝炎临床疗效观察

目的：观察胸腺五肽治疗重型肝炎临床疗效。方法：2000年8月-2001年8月间，我院住院治疗的重型肝炎患者40例，应胸腺五肽注射液治疗。疗程最短14天，最长60天，平均21天。结果：胸腺五肽治疗后纳差有效率为85.21％，腹胀有效率为80.3％，乏力有效率为71.62％，鼻衄有效率为84.7％，牙龈出血有效率为94.7％。重型肝炎患者的血清总胆红素（TB）、ALT、AST的降幅明显，TB、ALT、AST及凝血酶原时间的复常率均大于60％。用后患者无明显不良反应。结论：胸腺五肽治疗重症肝炎疗效较好。     

免疫增强剂胸腺五肽临床超说明书用药调查分析

目的 了解胸腺五肽在临床超说明书用药现状,为胸腺五肽作超说明书用药备案提供依据。方法 采用回顾性研究法,调查和审核某三甲中医院2020年11月1日至2021年10月31日门诊使用胸腺五肽的2 367张处方,整理出该药临床超说明书用药情况。结果 注射用胸腺五肽门诊处方超说明书用药发生率为75.58%(1 789/2 367),其中超适应证用药发生率为77.98%(1 395/1 789),超年龄范围用药发生率为1.17%(21/1 789),超用法用量发生率为62.88%(1 125/1 789)。结论 注射用胸腺五肽门诊用药存在超适应证、超剂量、超年龄范围等超说明书用药情况,需加强监控和管理,促进胸腺五肽超说明书用药备案。     

胸腺五肽治疗慢性乙型肝炎56例

目的：探讨胸腺五肽治疗慢性乙型肝炎的疗效及不良反应。方法：选择慢性乙型肝炎患111例，随机分成两组，其中对照组55例采用综合治疗；治疗组56例在综合治疗基础上加用胸腺五肽1mg，静脉滴注，每日1次，3月为一疗程。结果：疗程结束时，治疗组HBeAg和HBV－DNA的阴转率为51．9％和55．4％，而对照组为7．3％和10．9％，治疗组的疗效明显优于对照组，二有非常显性差异（P＜0．01），治疗组未见明显不良反应。结论：胸腺五肽治疗慢性乙型肝炎，安全有效，值得临床推广。     

胸腺五肽鼻喷雾剂的研制

目的研究胸腺五肽鼻喷雾剂的制备方法并建立质量控制方法。方法确定处方组成及制备工艺。采用紫外分光光度法测定胸腺五肽的含量。结果胸腺五肽平均回收率为100.06%,RSD=0.13%(n=5);含量测定方法可行。结论该制剂制备工艺简单,质量控制方法可靠,质量稳定。     

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.