药铜宫内节育器抗生育作用的实验研究

以雌性家兔交配后生殖道内精子数及其活率影响为指标，观察比较了复合型药铜宫内节育器（ＬＮＧ＿Ｃｕ－ＩＵＤ）与含铜、含孕激素宫内节育器（Ｃｕ－ＩＵＤ、ＬＮＧ－ＩＵＤ）的抗生育作用。结果表明，３种ＩＵＤｓ均能明显减少子宫和输卵管中精子数，并降低其活率，其中以药铜宫内节育器最为显著，放置ＬＮＧＣｕ－ＩＵＤ、Ｃｕ－ＩＵＤ、ＬＮＧ－ＩＵＤdisplay structure     

复方炔诺孕酮缓释微囊注射液的研究

采用复凝聚法制备复方避孕药［左炔诺孕酮（ＬＮＧ）和雌二醇戊酸酯（ＥＶ）之重量比为５：３］缓释微囊肌肉注射液。囊径１０～６０μｍ的占８２．６％，室温贮存５年后，囊形、囊径分布和含量几乎无变化。体外以５０％乙醇液或含５％乙醇的ｐＨ７．４磷酸盐缓冲液作释放介质时，微囊注射液释放ＬＮＧ均服从零级释放规律，ｋ＿ｒ分别为７２μｇ／ｈ、３４μｇ／ｄ，ｔ＿（５０）为１０．４ｈ、３２．３ｄ，释放量对时间的线性关系良好，与破囊后的注射液相比有极显著差异。微囊注射液具有明显的缓释作用。     

用HPLC法同时测定皮肤渗透液中18-甲墓炔诺酮和雌二醇的含量

用ＨＰＬＣ法同时测定皮肤渗透液中１８－甲基炔诺酮和雌二醇的含量。色谱柱：Ｓｈｉｍ－ＰａｃｋＣＬＣ－ＯＤＳ，检测波长：２８０ｎｍ（０—７．２０ｍｉｎ），２４２ｎｍ（７．２１—８．９０ｍｉｎ），流动相：甲醇－水（７５：２５）．线性范围均为０．２～４．０μｇ／ｍｌ（ｒＬＮＧ＝０．９９９９，ｒＥ２＝０．９９９８）；最低检测量ＬＮＧ为１ｎｇ，Ｅ２为５ｎｇ，ＬＮＧ与Ｅ２在等浓度条件下平均回收率分别为ＬＮＧ１００．６４±０．７５％，Ｅ２　９９．９９±０．８４％，日内ＲＳＤ分别为ＬＮＧ０．４４％，Ｅ２１．０６％，日间ＲＳＤ分别为ＬＮＧ０．７８％，Ｅ２　１．３０％。该方法简便、快速，结果准确。     

DNA重组hGH的生物测定方法的探讨 Ⅰ．去垂体大鼠体重增加法

为用于ＤＮＡ重组ｈＧＨ的生物测定，本文探讨了未成年去垂体大鼠体重增加法。实验表明：牛生长激素ｂＧＨ在０．００４～０．５００ＩＵ／鼠、ｄ，人生长激素ｈＧＮ在０．０１５～０．１３５ＩＵ／鼠、ｄ剂量范围内ｌｏｇ剂量（Ｘ）与反应（Ｙ）呈直线关系。６０～８０ｇ去垂体大鼠，每天给药２次，连续给药４ｄ或６ｄ为最佳实验条件。通过多批进口和国产ＤＮＡ重组ｈＧＨ产品的生物测定，说明用该法检测ｒｈＧＨ是颇为实用的方法之一。     

他莫昔芬软膏在3种基质听体外透皮的释药比较

测定１％他莫昔芬在３种软膏基质听体外透皮释放都优于凡士林软膏基质评价３种软膏基质对主药经皮渗透的影响。方法：以人离体皮肤为渗透释药模型，试验用Ｆｒａｎｚ扩散池，２３５ｎｈｍ处ＵＶＩＭＪ ＰＧ 。ＸＦＪＳ：Ｄ ＭＹＩ ＦＧＨＧＳＳ 、ＢＣＴＩＮＮＬＬＦＧ ＳＧＹＢＴ ＢＣＴＩＵＤＣＴＮＮＬＬＯＱＤ ３ＴＫＨ ＡＤ ＲＦＭ Ｋ ＷＢ ＡＪＤ ＡＪＦ ＳＱＡ     

5—单硝酸异山梨醌制剂溶出度的研究

对５－单硝酸异山梨酯两种市售制剂的溶出度进行ＲＰ－ＨＰＬＣ外标法测定。流动相为甲醇－水，检测波长２２０ｎｍ，线性范围２－８０μｇ／ｍｌ，最低检测浓度０．１μｇ／ｍｌ，ＲＳＤ小于１％。经非线性回归，证实缓释制剂的释药符合一级方程Ｄｔ＝Ｄｍａｘ「７０％（１－ｅ＾－ｋ（ｔ＝ｔ０））＋３０％」。     

尿激酶与前列腺素E1联用对急性心肌梗死早期静脉溶栓的临床观察

目的 探讨尿激酶（ＵＫ）和前列腺素（ＰＧＥ１）联合给药对急性心肌梗死（ＡＭＩ）６ｈ内入院患进行静脉溶栓的疗效观察。方法 分为ＵＫ＋ＰＧＥ１组（３２例）及ＵＫ组（４９例）;ＵＫ用量为２万Ｕ／ｋｇ,ＰＧＥ１用量为３００￣４００μｇ／次。两组龄、性别、发病至用药时间艾无差异。结果 联用组再通２３例,再通率６１．９％     

5-单硝酸异山梨酯制剂溶出度的研究

对５－单硝酸异山梨酯两种市售制剂的溶出度进行ＲＰ－ＨＰＬＣ外标法测定。流动相为甲醇－水（１∶３），检测波长２２０ｎｍ，线性范围２～８０μｇ／ｍｌ，最低检测浓度０．１μｇ／ｍｌ，ＲＳＤ小于１％。经非线性回归，证实缓释制剂的释药符合一级方程Ｄｔ＝Ｄｍａｘ［７０％（１－ｅ－ｋ（ｔ－ｔ０）＋３０％］。     

胎儿宫内生长迟缓时孕妇血及脐血中一氧化氮水平与胎儿脐血流S／D？…

目的 了解胎儿宫内生长迟缓（ＩＵＧＲ）时，孕妇血及脐血中一氧化氮（ＮＯ）水平与胎儿脐血流Ｓ／Ｄ值的关系，以进一步探讨ＩＵＧＲ时胎盘循环阻力增高的原因。方法 对３３例妊娠合并胎儿宫内生长迟缓（ＩＵＧＲ组）及３２例正常孕妇（对照组），用镉还原显色法测定母血及脐血ＮＯ水平，超声多普勒测定胎儿脐血流Ｓ／Ｄ值。结果 ＩＵＧＲ组母血及脐血ＮＯ水平均明显低于对照组（Ｐ〈０．０１，Ｐ〈０．０１），母血与脐血ＮＯ水     

异丙肾上腺素透皮控释贴剂的研究

本文将异丙肾上腺素研制成胶粘剂层扩散控制型透皮贴膜剂。建立二阶导数紫外分光光度法，考察了药物贴片的体外释放速率及经离体鼠皮的渗透速率。结果表明由胶粘剂层控制的贴片对药物有良好的控制作用，药物以零级动力学方式释放和渗过皮肤。体外释药速率及离体皮肤渗透速率分别为１９．７９μｇ／（ｃｍ￣２·ｈ）和１８．８９μｇ／（ｃｍ￣２·ｈ），且可持续稳态释放２４ｈ以上。     

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.     

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.