盐酸氟西泮

本品为1-[α-(二乙氨基)乙基]-5-(α-氟苯基)-7-氮-1,3-二氢-2H-1,4苯并二氮杂-α-酮二盐酸盐。按干燥品计算,含C₂₁H₂₃ClFN₃·2HCl不得少于98.5%。     

丙酸氯倍他索

本品为16β甲基11β-羟17(1-氧代丙氧基)-9-氟-21-氯-孕甾-1,4-二烯-3,20-二酮。按干燥品计算,含C₂₅H₃₂C1FO₅应为97.0~103.0钩。[性状]本品为类白色或微黄色结晶性粉末。     

硝酸益康唑

本品为1-[2,4-二氯β- (4-氯苄氧基)苯乙基]咪唑硝酸盐,按干燥品计算,含C₁₈H₁₅Cl₃N₂O·HNO₃不得少于98.5%。     

新型含二硫键和硫酯键的乙酰半胱氨酸衍生物的合成与抗肝损伤活性评价

目的 设计、合成N-乙酰半胱氨酸衍生物,并评价目标化合物对H₂O₂诱导的LO2细胞氧化损伤的保护作用。方法 以L-半胱氨酸和N-乙酰半胱氨酸为起始原料,采用酰氯酯化法合成具有全新结构的乙酰半胱氨酸衍生物;以H₂O₂损伤LO2人肝细胞建立体外氧化损伤模型,利用CCK-8法检测不同浓度H₂O₂对LO2细胞存活率的影响,并检测细胞上清中MDA含量和SOD活性。结果 共合成了6个全新结构的N-乙酰半胱氨酸衍生物,其结构经¹H-NMR、¹³C-NMR、ESI-MS确证,目标化合物能够抑制H₂O₂诱导的LO2氧化损伤,并能够降低MDA含量和提高SOD活性（P<0.01或P<0.05）。结论 本研究快速、高效地合成了N-乙酰半胱氨酸系列衍生物,目标化合物对体外肝细胞损伤具有保护作用。     

洋参抗衰合剂对H2O2诱导HepG2细胞氧化损伤的保护作用

目的 考察洋参抗衰合剂对H₂O₂致HepG2细胞氧化应激损伤的保护作用,并初步分析洋参抗衰合剂对H₂O₂诱导HepG2细胞氧化损伤的保护机制。方法 以H₂O₂诱导培养的HepG2细胞为模型,检测洋参抗衰合剂对HepG2细胞中谷胱甘肽(glutathione,GSH)含量、过氧化氢酶(catalase, CAT)活力和丙二醛(malondialdehyde, MDA)含量的变化,分析洋参抗衰合剂的抗氧化作用。结果 随着洋参抗衰合剂质量浓度的增加,H₂O₂诱导HepG2细胞的谷胱甘肽(GSH) 和过氧化氢酶(CAT)含量上升,丙二醛(MDA)的含量有所下降。结论 洋参抗衰合剂对H₂O₂诱导HepG2细胞损伤有抗氧化作用,其机理可能是通过促进还原物质的合成,增加抗氧化酶的活性进而减少脂质过氧化物。     

耳叶牛皮消中的苯乙酮类化合物及其抗氧化活性研究

目的 研究耳叶牛皮消(萝藦科)Cynanchum auriculatum Royle ex Wight(asclepiadaceae)块根的化学成分及其抗氧化活性。方法 药材提取物分部萃取后采用硅胶、Sephadex LH-20柱层析等进行分离纯化,通过理化性质和光谱分析鉴定结构。在H₂O₂刺激条件下,研究化合物对PC12细胞中超氧化物歧化酶(SOD)活性、过氧化氢酶(CAT)活性以及谷胱甘肽过氧化物酶(GSH-Px)活性的影响。结果 从耳叶牛皮消中分离得到了5个苯乙酮类化合物,分别鉴定为cynandione A (I)、cynandione B (II)、cynandione C (III)、cynanchone A (IV)、cynantetrone (V)。H₂O₂能降低SOD、CAT和GSH-Px三种抗氧化酶活性,而耳叶牛皮消中的苯乙酮类化合物可抑制H₂O₂引起的氧化损伤。结论 耳叶牛皮消中的苯乙酮类化合物具有抗氧化活性。     

海洋环肽stylissamide Ⅰ的全合成研究

目的 采用固相合成/液相环化方法合成海洋环肽stylissamide Ⅰ。方法 以2-氯三苯甲基氯树脂（简称二氯树脂）为载体,选用6-氯苯并三氮唑-1,1,3,3-四甲基脲六氟磷酸酯（HCTU）和N,N-二异丙基乙胺（DIPEA）为缩合试剂依次连接9-笏甲氧羰基保护的氨基酸,在三氟乙醇（TFE）的作用下将直链肽从树脂上切割下来,然后使用（3H-1,2,3-三唑并吡啶-3-氧基）三-1-吡咯烷基六氟磷酸盐（PyAOP）,N-羟基-7-氮杂苯并三氮唑（HOAt）和N-甲基吗啡啉（NMM）在溶液中完成环合,最后在三氟乙酸（TFA）的处理下脱去侧链保护基,获得环肽粗品。经反相高效液相色谱对所合成的环肽粗品进行纯化,终产物纯度98.9%。通过高分辨质谱、600 MHz ¹H-NMR和¹³C-NMR鉴定,确定所合成环肽为目标环肽。结果 首次完成海洋环肽stylissamide Ⅰ的全合成,总收率为67%。结论 此法具有快捷、简便、高效的特点,较好地为stylissamide Ⅰ的固相全合成提供了参考。     

单盐酸氟西泮

本品为1-[2-(二乙基氨基)乙基]-5-(2-氟苯基-7-氯-1,3-二氢-2H-1,4-苯并二氮杂-2酮酸盐。按干燥品计算,含C₂₁H₂₃C1FN₃O·HCl应为98.5~101.0%,含氯离子为8.2~8.5%。[性状]本品为白色或类白色结晶性粉末,无臭或几乎无臭。     

千金藤啶碱的全合成

目的 合成天然产物千金藤啶碱（SPD）。方法 以3-羟基-4-苄氧基苯乙酸为原料,经内酯化、甲基化得到7-苄氧基-8-甲氧基苯并二氢异吡喃-3-酮(3),化合物3与3-甲氧基-4-苄氧基苯乙胺缩合得酰胺衍生物N-(4-苄氧基-3-甲氧基苯乙基)-2-(4-苄氧基-2-羟甲基-3-甲氧基苯基)乙酰胺(5),5经Bischler-Napieralski环合、硼氢化钠还原得2,10-二苄氧基-3,9-二甲氧基-5,8,13,13a-四氢-6H-二苯并[a, g]喹嗪(6),6经Raney-Ni催化氢化脱苄基得到千金藤啶碱。结果与结论 该合成路线较短,操作简单,反应条件温和,成本较低,且在保证收率的前提下避免了高危险性的重氮甲烷的使用,目标化合物SPD及其中间体的结构经核磁共振氢谱和质谱确证。     

国家食品药品监督管理局国家药品标准修订件-佐匹克隆

本品为6-(5-氯吡啶-2-基)-7-[(4-甲基哌嗪-1-基)羰氧基]-5,6-二氢吡咯[3,4-b]吡嗪-5-酮。按干燥品计算,含C₁₇H₁₇ClN₆O₃不得少于98.5%。     

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.