以经皮微渗析技术研究奥旦西酮的大鼠在体经皮吸收

目的：研究奥旦西酮的经皮渗透性,并考察透皮吸收促进剂月桂氮　酮(azone)对其经皮渗透性的影响。方法：以大鼠为实验模型动物,应用经皮微渗析在体取样技术进行实验。探针的在体回收率以反向渗析法测定。结果：Azone可以极大地提高药物在渗析液及皮肤中的浓度,2%和5%的azone分别使渗析液中药物的稳态流量从0.001 μg.h^-1提高到1.281和1.824 μg.h^-1。结论：经皮微渗析技术是研究药物在体经皮吸收的有力工具。Azone是奥旦西酮经皮吸收的优良促进剂。     

渗透促进剂对蛇床子素透皮吸收影响的研究

目的 研究渗透促进剂对蛇床子素的体外经皮渗透的影响；方法 将蛇床子有效部位制成饱和生理盐水溶液，采用Walia-Chien扩散池考察了Azone、薄荷醇及土荆芥油三种渗透促进剂对蛇床子素经离体鼠皮渗透性的影响；结果 应用土荆芥油、薄荷醇和Azone为渗透促进刑，药物的稳态流量与对照组比较均有提高，增渗倍数分别为3．09、3．41及4．38；药物的扩散系数分别提高为1．10、2．18及6．30倍，但分配系数却分别降低为0.309、0.341及0.438；结论 三种渗透促进别的作用机理主要为改变角质层的通透性，减低了药物经皮肤渗透的阻力，提高了药物在皮肤角质层的扩散系数。     

不同浓度的月桂氮蕈酮对双氯芬酸钠凝胶剂透皮吸收的影响

目的通过动物离体透皮吸收试验，选择双氯芬酸钠凝胶剂中最佳浓度的月桂氮革酮(氮酮，Azone)作为渗透促进剂。方法采用改良的Franz扩散装置，以离体鼠皮为屏障、生理盐水为接受介质，研究了不同浓度的月桂氮革酮(0％、1％、2％、3％、5％Azone)对双氯芬酸钠凝胶剂透皮吸收的影响。结果双氯芬酸钠凝胶剂12h累积透皮释药百分率依次为38．42％、62．35％、72．80％、32．10％、55．36％。结论Azone促进双氯芬酸钠凝胶剂透皮释药的最大浓度为2％，筛选出2％月桂氮革酮作为促进剂，制备了具有良好经皮吸收性能的双氯芬酸钠凝胶剂。     

胰岛素体外透皮特性研究

目的 考察胰岛素透皮吸收特性及透皮促进剂对其透皮行为的影响。方法 通过V-C扩散池，用紫外分光光度法测定胰岛素的透皮吸收动力特性及透皮促进剂的促进作用。结果 胰岛素经离体小鼠、家兔、大鼠和人体皮肤的渗透系数分别为16．37，17．54，8．23和9．15。而氮酮(Azone)、冰片、油酸有明显的促透作用，其中3％的Azone和2％的冰片使渗透系数分别增加了4．9和6．1倍。结论 胰岛素在大鼠皮肤中渗透系数与人体皮肤接近，冰片和Azone具有促进药物渗透作用。     

微渗析技术用于盐酸奥旦西酮的大鼠在体透皮吸收研究

本文进行了微渗析探针的体内、外校正,浓差法和反渗析法分别用于测定探针的体内和体外回收率。在探针校正的基础上,研究了盐酸奥旦西酮（ＯＮ）丙二醇（ＰＧ）溶液的大鼠在体经皮吸收及渗透促进剂油酸（ＯＡ）的作用。微渗析样品用高效液相法测定。结果证明：探针的体外回收率（３５．４６±４２％）和体内回收率（３２．５３±１．８％）没有显著的差别（Ｐ＞０．１）。以 ２％和５％ＯＡ的ＰＧ溶液为渗透促进剂时,ＯＮ在渗析液和真皮中达到坪浓度的时间分别为３．５及１．５ ｈ：后者的坪浓度约是前者的两倍。当ＯＡ的浓度从０提高到２％、 ５％时,药物的稳态传递速度从０．００１增大到０．０３０和０．０５８μｇ·ｈ~－１。实验证明 ＯＡ对于ＯＮ的大鼠在体透皮吸收是一种有效的促进剂。     

不同透皮促进剂对丹参贴膏离体透皮吸收的影响

本文报道了4种透皮促进剂3％月桂氮卓酮（Azone）＋5％丙二醇，3％Azone，5％丙二醇和5％二甲基亚砜（DMSO）对丹参贴膏中两种主要有效成分丹参素和原几条醛透皮吸收的影响。采用离体鼠皮为皮肤模型，实验装置应用自行设计的单室透皮扩散池，检测方法为高效液相色谱法。结果表明，4种透皮促进剂均可不同程度地促进丹参贴膏的透皮吸收效果，其中3％Azone＋5％丙二醇组成的二元透皮促进剂作用最显著。     

氮酮和薄荷醇对特比萘芬体外经皮渗透性的影响

目的 研究透皮促进剂氮酮和薄荷醇对外用抗真菌药特比萘芬体外经皮渗透性的影响。方法 在离体透皮实验装置上进行透皮吸收试验和贮库效应的研究，采用正交函数分光光度法消除皮肤浸出物的吸收干扰。结果 1％氮酮和1％薄荷醇对特比萘芬经皮渗透有明显促进作用，且两者合用可明显缩短时滞。结 论薄荷醇和氮酮对特比蔡芬体外经皮吸收具有显著的促进作用，并能增加贮库效应。     

蛇床子有效部位水醇凝胶中蛇床子素体外经皮渗透的评价

以蛇床子有效部位中的主要成分蛇床子素为定量指标对蛇床子水醇凝胶剂的经离体人皮的透皮性能进行了研究，考察了Azone、薄荷醇和土荆芥油三种不同渗透促进剂的作用。实验结果表明含有三种渗透促进剂的处方中药物的稳态流量与对照组比较均有提高，增渗倍数分别为3.10、2.00和1.25。含有Azone、薄荷醇和土荆芥油为渗透促进剂的处方中药物的扩散系数与对照组相比，分别提高为5.54、4.73和2.13倍，但分配系数却分别降低为0.56、0.46和0.59倍。结果提示三种渗透促进剂的作用机理主要为改变角质层的通透性，减低了药物经皮肤渗透的阻力，提高了药物在皮肤角质层的扩散系数。     

盐酸多西环素脂质体凝胶剂的制备与评价

以薄膜-振荡分散法制备盐酸多西环素脂质体，再以卡波姆为基质制备脂质体凝胶剂。比较了制品及普通凝胶剂对离体鼠皮的经皮渗透作用。结果表明，制品平均粒径为200～300nm，包封率为80．1％。体外透皮实验中，脂质体凝胶剂24h的药物浓度为156，7μg／ml，明显高于普通凝胶剂（83．3μg／m1）。     

氮酮对5—FU透皮吸收影响的研究

本文采用静态简单小室装置以5-FU 为模型药物,初步研究了氮酮(Azone)对5-氟尿嘧啶(5-FU)的透皮吸收促进作用及作用机理.实验证明,含3%Azone 的5-FU 液24h 透皮吸收率为81.4±5.47%,不含Azone 及含3%DMSO 的5-FU 液24h 透皮吸收率分别为12.7±0.262%和16 6±1.64%,含3%Azone 的5-FU 液24h 时从真皮侧向表皮侧穿透吸收率为15.2±1.41%.     

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.     

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.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.     

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.