吲哚美辛锌胶囊在兔血浆中药代动力学研究

用ＨＰＬＣ测定了兔口服吲哚美辛锌及吲哚美辛胶囊后血浆中吲哚美辛的浓度，其药－时曲线均符合一室开放模型，数据经３Ｐ８７计算机程序处理拟合得吲哚美辛锌及吲哚美辛药动学参数分别为：Ｃｍａｘ２．０８８ｍｇ／Ｌ，２．６６１ｍｇ／Ｌ；Ｔｍａｘ５．２２７ｈ，３．７０４ｈ；Ｋｅ０．１２３ｈ－１，０．１７２ｈ－１；Ｋａ０．２８９ｈ－１，０．４５９ｈ－１；Ｔ２／２（ａ）２．４０１ｈ，１．５０８ｈ；Ｔ１／２（ｅ）５．６１７ｈ，４．０４０ｈ；ＡＵＣ３１．９０５ｍｇ·ｈ／Ｌ，２７．９０３ｍｇ·ｈ／Ｌ。相对生物利用度为１１４％。     

吲哚美辛缓释胶囊单剂量与多剂量达稳态时的相对生物利用度

采用反相高效液相色谱法测定１１名健康志愿受试者单剂量口服７５ｍｇ和多剂量口服吲哚美辛缓释胶囊和吲哚美辛片后，吲哚美辛血药浓度变化情况。测得单剂量口服７５ｍｇ吲哚美辛缓释胶囊与吲哚美辛片的达峰时间分别是４．０ｈ与１．５ｈ，峰浓度分别是１．０２μｇ·ｍｌ－１与３．７μｇ·ｍｌ－１，吲哚美辛缓释胶囊的相对生物利用度为１０２％。测得多剂量口服吲哚美辛缓释胶囊与吲哚美辛片达稳态后的Ｃｍｉｎ分别是０．２０８μｇ·ｍｌ－１与０．２６３μｇ·ｍｌ－１，Ｃｍａｘ分别是１．２６μｇ·ｍｌ－１与１．２２６μｇ·ｍｌ－１，Ｔｍａｘ分别为２．７７ｈ与１．８２ｈ，ＦＩ分别是１４０．８１％与１２８．２１％。以ＡＵＣ为指标，经统计分析，吲哚美辛缓释胶囊与吲哚美辛片在单剂量和多剂量达稳态时是生物等效制剂。     

复方吲哚美辛栓直肠给药对产科手术切口的止痛作用

目的：观察复方吲哚美辛栓治疗分娩术后切口痛的疗效。方法：对４５例会阴切开术和４０例剖宫产的分娩产妇，前者在产后次日直肠给复方吲哚美辛栓１枚（每枚含吲哚美辛７０ｍｇ和沙丁胺醇１．２ｍｇ），ｑｄ×３ｄ；后者在术日麻醉效果消失后给药，用法同前，共４次。对照组６７例，其中３５例是会阴切开术，在分娩次日给安乃近１片（０．５ｇ／片）ｐｏ，ｑｄ×３ｄ，３２例剖宫产，在术日麻醉效果消失后给丁丙诺啡１支（１００ｍｇ／支）ｉｍ，ｑｄ×３ｄ。结果：止痛作用达优、良的有效率，复方吲哚美辛组各为１００％和９５％，对照组各为５４％和４１％。２相关组疗效相比Ｐ皆＜０．０１。结论：复方吲哚美辛栓对产科术后镇痛的效果良好。     

吡罗昔康凝胶剂和吲哚美辛擦剂治疗骨关节炎的比较

目的：比较吡罗昔康凝胶剂和吲哚美辛擦剂对骨关节炎（ＯＡ）的疗效。方法：６０例ＯＡ病人随机分为２组，吡罗昔康组３０例（男性１４例，女性１６例；年龄５７±ｓ７ａ，病程４±４ｍｏ），每一疼痛区表面涂擦吡罗昔康凝胶１ｇ，ｑｉｄ×２ｗｋ。吲哚美辛组３０例（男性１０例，女性２０例；年龄５６±８ａ，病程２±３ｍｏ），每一疼痛区表面涂擦吲哚美辛擦剂１ｍＬ，ｑｉｄ×２ｗｋ。结果：总有效率吡罗昔康组为９０％，吲哚美辛组为７７％（Ｐ＜０．０５）。结论：吡罗昔康凝胶剂治疗ＯＡ疗效优于吲哚美辛擦剂。     

阿西美辛缓释胶囊的药物代谢动力学

建立了同时测定人血清中阿西美辛和吲哚美辛的ＨＰＬＣ方法,研究了阿西美辛缓释胶囊的药代动力学。结果表明,１２ 名健康受试者口服单剂量阿西美辛缓释胶囊（９０ ｍ ｇ）时,ｔｍａｘ＝ ３．０８±１．０８ ｈ,Ｃｍａｘ＝ １．０１２±０．２８６ μｇ／ｍ ｌ,ｔ１／２（ｋｅ）＝ ８．８８４±２．０８６ ｈ,ＡＵＣ０－∞＝ ６．５２５±１．９９２ μｇ·ｈ／ｍ ｌ     

复方吲哚美辛栓直肠给药对产科手术切口的止痛作用

目的：观察复方吲哚美栓治疗分娩术后切口痛的疗效。方法：对４５例会阴切开术和４０例中产的分娩产妇，前在产后次日直肠给复方吲哚美辛栓１枚（每枚含吲哚美辛７０ｍｇ和沙丁胺醇１．２ｍｇ），ｑｄ×３ｄ；后在术日麻醉效果消失后给药，用法同前，共４次，对照组６７例，其中３５例是会阴切开术，在分娩次日给安乃近１片（０．５ｇ／片）ｐｏ，ｑｄ×３ｄ，３２例剖宫产，在术日麻醉效果消失后给丁丙诺啡１支（１００ｍｇ／支     

大鼠鼻腔吸收吲哚美辛

研究吲哚美辛经大鼠鼻腔给药作用的可行性。方法：用高效液相色谱仪测定血浆中吲哚美辛的药浓变化，比较大鼠吲哚美辛３ｍｇ．ｋｇ＾－１水溶液经口服、静脉与鼻腔给药的吸收特点。结果：鼻腔约药达峰时间为０．０８ｈ，几乎接近于静脉给药；、峰浓度为２０．０ｍｇ．Ｌ＾－１，     

吲哚美辛对急性颅脑损伤颅内压的影响

目的：探讨吲哚美辛对急性颅脑损伤颅内压（ＩＣＰ）的影响。方法：急性颅脑损伤病人３０例（男性２１例，女性９例；年龄３２±ｓ９ａ），在常规治疗（２０％甘露醇、细胞色素Ｃ、脑活素静脉滴注）基础上采用吲哚美辛片２５ｍｇ，ｐｏ，ｔｉｄ，共７ｄ；另设急性颅脑损伤病人３０例（男性２０例，女性１０例；年龄３１±８ａ）仅用常规治疗作对照。分别测定２组治疗前后ＩＣＰ和格拉斯哥昏迷分级表（ＧＣＳ）计分的变化。结果：治疗７ｄ后，前组ＩＣＰ显著低于后组（Ｐ＜０．０１），而ＧＣＳ计分前组显著高于后组（Ｐ＜０．０５）。结论：吲哚美辛具有降低急性颅脑损伤ＩＣＰ和促进脑功能恢复的作用。     

布洛芬缓释胶囊与吲哚美辛治疗急性风湿性关节炎的疗效比较

目的：比较布洛芬缓释胶囊与吲哚美辛治疗急性风湿性关节炎的疗效。方法：７２例急性风湿性关节炎病人分２组，３６例（男性１９例，女性１７例，年龄３２±ｓ７ａ）用布洛芬缓释胶囊６００ｍｇ，ｐｏ，ｂｉｄ；另３６例（男性２０例，女性１６例，年龄３１±９ａ）用吲哚美辛５０ｍｇ，ｐｏ，ｔｉｄ，２组均经３ｗｋ治疗。结果：布洛芬缓释胶囊和吲哚美辛的有效率分别为９５％和７０％，有显著差异Ｐ＜０．０５。消化道副作用布洛芬缓释胶囊较吲哚美辛为少。结论：布洛芬缓释胶囊治疗急性风湿性关节炎的疗效明显高于吲哚美。     

吲哚美辛栓治疗高热患儿疗效观察

按５（年龄十１）ｍｇ给予５８例高热患儿吲哚美辛肛栓，与ｉｍ常规剂量安痛定的５６例患儿相比较，用药后１，２，４，６，８和１０ｈ两组患儿体温均数有显著差异（Ｐ＜０．０１）。表明吲哚美辛栓退热确实，且应用简便、无痛苦、副作用小。     

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.

---

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.     

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.