促进剂预处理皮肤对环吡酮胺经皮渗透的影响

目的：考察透皮促进剂对环吡酮胺经皮渗透的影响,方法：用透皮促进剂预处理离体小鼠皮肤,以改良的Franz扩散装置进行体外渗透实验,结果：环吡酮胺经皮渗透符合零级动力学过程,几种透皮促进剂的促渗作用大小依次为月桂氮zhuo酮－丙二醇（1：1）＞二甲基亚砜＞月桂氮zhuo＞水溶性月桂氮zhuo酮＞N－甲基吡咯烷酮＞薄荷油,结论：体外实验证明,透皮促进剂可增加环吡酮胺的透皮吸收。     

不同透皮促进剂对环吡酮胺和水杨酸体外经皮渗透性的影响

目的：以环吡酮胺和水杨酸为模型药物。研究透皮促进剂对外用抗真菌药的促透特性。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。结果：1%氮酮和1%薄荷醇联用对环吡酮胺经皮渗透的促进作用明显高于其它组，1%的薄荷醇对水杨酸促透效果最佳。而由1%氮酮。2.5%丙二酮，2.5%油酸，1%薄荷醇合用对环吡酮胺的体外经皮渗透虽具有明显的促进作用和时滞明显缩短。但是与二联使用透皮促进剂比较并无明显优点。结论：薄荷醇和氮酮对环吡酮胺和水杨酸体外经皮吸收具有显的促进作用。两联用对脂溶性化合物环吡酮胺的促透作用更明显。     

非洛地平透皮给药的研究

采用Ｆｒａｎｚ扩散池,研究了非洛地平（１）的体外透皮渗透情况。结果表明：１能透过离体小鼠皮肤,且月桂氮酮（２）对其透皮吸收有一定的促进作用。含０．２％２的１涂膜剂在各时间下的透皮吸收量比不含２者都有一定的提高。用抛物线拟合法建立了不同时间下不同浓度的２对１透皮渗透量的数学模型,最佳浓度为０．１７２±０．０４２％。１涂膜剂的透皮渗透为零级过程。     

高效液相色谱法测定环吡酮胺乳膏中药物的含量及其体外透皮释放量

目的采用高效液相色谱（HPLC）法测定环吡酮胺乳膏的含量及体外透皮量.方法色谱柱为Intersil ODS 3 C18柱（4.6 mm×200 mm,5 μm）,流动相为乙腈 0.1%乙二胺四醋酸二钠溶液（70：30）,检测波长304 nm.体外透皮释放实验采用单室Franz扩散池,大鼠皮肤,自制乳膏与市售乳膏的透皮结果对比.结果环吡酮胺在20～180 μg&;#8226;mL 1范围内,线性关系良好（r＝0.999 8）,平均回收率为99.7%,RSD为0.69%.体外透皮释放量与时间呈良好的线性关系,相关因素为0.967 9.自制乳膏与市售乳膏的透皮结果差异无显著性.结论该法测定环吡酮胺乳膏药物含量及体外透皮释放量操作简便,快速准确.软膏基质和皮肤中成分对测定无干扰.     

雌二醇透皮给药系统控释机理研究

含雌二醇的新颖膜控骨架型透皮给药系统（Ｅ２－ｍＴＤＤＳ），其人皮肤体外渗透动力学实验证明，雌二醇的透皮渗透呈零级动力学，且渗透速率与限速膜厚度的倒数呈良好线性关系（ｒ＝０．９９４）。因而该体系具有膜控型控释机理。     

雌二酵透皮给药系统控释机理研究

含雌二醇的新颖膜控骨架型透皮给药系统（Ｅ２－ｍＴＤＤＳ），其人皮肤体外渗透动力学实验证明，雌二醇的透皮渗透呈零级动力学，且渗透速率与限速膜厚度的倒数呈良好线性关系（ｒ＝０．９９４）。因而该体系具有膜型控释机理。     

高效液相色谱法测定环吡酮胺乳膏中药物的含量及其体外透皮释放量的研究

目的：探讨环吡酮胺乳膏应用高效液相色谱法进行药物含量与体外透皮释放量测定的效果。方法检测波长305 nm;流动相：乙腈-0.1%乙二胺四醋酸二钠溶液（70：30）;Kromasil C18色谱柱;应用单室Franz扩散池、大鼠腹皮进行透皮释放实验,对比市面乳膏与自制乳膏的透皮结果。结果环吡酮胺范围介于20~180μg/mL间,平均回收率99.8%,RSD为0.70%,线性关系较好（r=0.9997）,相关因素为0.9673,市面乳膏与自制乳膏透皮结果差异无统计学意义（P〉0.05）。结论采用高效液相色谱法测定环吡酮胺乳膏不会受皮肤成分与软膏基质影响,且操作简便,准确率高,测定效果理想。     

透皮促进剂预处理皮肤对环孢素A经皮渗透的影响

目的：考察透皮促进剂对环孢素Ａ经皮渗透的影响。方法：用透皮促进剂预处理离体小鼠皮肤,以改良的Ｆｒａｎｚ扩散装置进行体外渗透实验。结果：环孢素Ａ经皮渗透符合零级动力学过程,几种透皮促进剂的促渗作用大小依次为月桂氮Ｚｈｕｏ酮－丙二醇（１：１）〉月桂氮Ｚｈｕｏ酮〉水溶性月桂氮Ｚｈｕｏ酮〉二甲基亚砜〉Ｎ－甲基吡咯烷酮〉薄荷油。结论：体外实验证明,透皮促进剂可增加环孢素Ａ的透皮吸收。     

环吡酮胺凝胶的制备与含量测定

目的 制备环吡酮胺凝胶剂,建立测定环吡酮胺凝胶剂中环吡酮胺含量的高效液相色谱法。方法 用卡波姆-940作基质,三乙醇胺为中和剂制备环吡酮胺凝胶剂。色谱柱：选用shim pack VP-ODS（4.6 mm×150 mm,5 μm）;流动相：甲醇 0.02 mol•L-1磷酸二氢钠溶液（60：40）,柱温30 ℃,流速1.0 mL•min-1,检测波长303 nm,以外标法峰面积定量。结果 在36.0～306.0 mg•L-1浓度范围内,峰面积与其浓度呈良好的线性关系,线性方程为：A＝7 684 029.359C－276 431.968 5 （n＝6）,r＝0.999 5。回收率、精密度均符合要求。结论 制备环吡酮胺凝胶可行,含量测定方法简便、灵敏、准确。     

环吡酮胺软膏治疗体股癣及花斑癣临床观察

目的：探讨环吡酮胺软膏对体癣、股癣及花斑癣的临床治疗效果。方法：应用1％环吡酮软膏治疗体癣31例，股癣40例，花斑癣41例，与2％硝酸咪康唑霜进行对比。结果：环吡酮胺组中体癣、股癣及花斑癣的治愈率分别是87．1％，82．5％和85．4％；硝酸咪康唑组的治愈率分别为73．3％，58．8％和53．1％。疗效差异显著。结论：环吡酮胺软膏治疗体癣、股癣和花斑癣的疗效明显优于硝酸咪康唑霜。     

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.