竹黄菌CGMCC 2201生产竹红菌素发酵培养基的优化

优化竹黄菌CGMCC 2201发酵培养基提高竹红菌素产量。方法 采用单因素试验确定培养基关键因素，利用中心组合设计与响应面分析法获得关键因素的最佳浓度，结合植物油添加试验，获得最优发酵培养基配方。结果 葡萄糖、硫酸铵、磷酸二氢钾、硫酸镁是发酵培养基中的关键因素。最优发酵培养基配方(g/L)：葡萄糖47.33，硫酸铵2.14，磷酸二氢钾2.87，硫酸镁1.68，豆油10。采用此发酵培养基的竹红菌素产量达257.66mg/L，与优化前培养基相比，提高了141.25%。结论 培养基是影响竹黄菌CGMCC     

药用真菌竹黄主要活性成分的异源生物合成

竹黄是我国一种重要的药用真菌资源,其主要活性成分竹红菌素类化合物已作为天然光敏剂广泛应用于食品、医药、农药等领域,其中竹红菌素软膏已用于临床。然而作为一种珍稀易危的物种,野生竹黄的资源非常有限。而竹红菌素结构复杂化学合成成本高,因此亟待一种有效的方法在保护竹黄野生资源的同时合理利用其药用价值。本文即采用合成生物学技术来获取竹黄中的主要活性成分,以期摆脱对野生资源的依赖。通过对竹黄菌Shiraia sp. cfcc 84681的全基因组进行细致的生物信息学分析,从中挖掘到一条竹红菌素生物合成的候选基因簇hpc;并成功构建了该基因簇的异源表达系统,获得一株产竹红菌素类化合物的重组菌株。该菌株主要产竹红菌甲素和异竹红菌甲素,这与野生竹黄提取物的主要成分基本一致。本研究有望为解决野生竹黄的资源短缺问题提供一种新的有效途径。     

竹黄菌CGMCC 2201生产竹红菌素发酵培养基的优化

优化竹黄菌CGMCC 2201发酵培养基提高竹红菌素产量。方法 采用单因素试验确定培养基关键因素,利用中心组合设计与响应面分析法获得关键因素的最佳浓度,结合植物油添加试验,获得最优发酵培养基配方。结果 葡萄糖、硫酸铵、磷酸二氢钾、硫酸镁是发酵培养基中的关键因素。最优发酵培养基配方(g/L)：葡萄糖47.33,硫酸铵2.14,磷酸二氢钾2.87,硫酸镁1.68,豆油10。采用此发酵培养基的竹红菌素产量达257.66mg/L,与优化前培养基相比,提高了141.25%。结论 培养基是影响竹黄菌CGMCC 2201生物合成竹红菌素的重要因素,发酵培养基优化后显著提高了竹红菌素的发酵产量。     

竹黄菌的液体发酵及生物学活性研究

目的研究竹黄菌的液体发酵最优条件及生物学活性。方法利用单因素实验方法比较不同培养条件对竹黄菌生长和产竹红菌素的影响,考察了竹黄菌发酵液抗菌和抗氧化的生物学活性。结果竹黄菌的较优培养条件为：蔗糖2.0%,葡萄糖3.0%,土豆20%,pH7.0,菌种活化后放置72h接种;竹黄菌发酵液对大肠杆菌、金黄色葡萄球菌、枯草芽孢杆菌、酿酒酵母、黑曲霉和黑根霉等均表现出了较强的抗性,对氧自由基和·OH的清除率分别为84.2%和76.32%。结论竹黄菌的液体发酵条件简单,发酵产物具有一定的广谱抗菌性能和抗氧化活性,在养殖业中有着良好的应用前景。     

国内新药品新剂型研究开发新动向

竹红菌脂质体固体粉末制剂 中国科学院化学研究所的研究人员开发出一种竹红菌脂质体固体粉末制剂。是利用磷脂、胆固醇等药用材料制成竹红菌素脂质体，可作为竹红菌素光动力药物临床的使用的静脉注射针剂。该品是再添加表面活性剂增加药物包容量。并在冷冻保护剂存在下低温、真空条件下冷冻干燥，获得更易保存和更高稳定性的固体（粉末状）竹红菌素脂质体。所使用的原料廉价易得、制造方法简单、易操作、不需特别设备、制备工艺成本低，包封率高：使用的材料生物可降解性好；所得到的固体竹红菌素脂质体稳定性高，可以容易地溶解于水、生理盐水、     

竹红菌素对小鼠皮肤致癌作用的实验观察

竹红菌素对小鼠皮肤致癌作用的实验观察纳冬荃，杨荣，曹跃华，张志杰，黄翠仙，蒋家雄竹红菌素是从野生竹红菌中提取并包括多种光敏色素的混合物；其中含有两种有效成份：竹红菌甲素（ｈｙｐｏｃｒｅｌｌｉｎＡ．ＨＡ）及竹红菌乙素（ＨｙｐｏｃｒｅｌｌｉｎＢ．ＨＢ），...     

竹红菌乙素对小鼠肝癌 H_(22)的抑制作用

竹红菌乙素对小鼠肝癌Ｈ２２的抑制作用王景祥何祖泽１朱丽青张黎明孙成春（济南军区总医院药理科，济南２５００３１）中国图书分类号Ｒ２８２．７１；Ｒ７３５．７；Ｒ９７９．１竹黄为肉痤菌科真菌竹黄的子座〔１〕。民间用于治疗风湿性关节炎、跌打损伤等症。笔者〔２...     

基因工程FR-008/杀念菌素脱羧衍生物发酵过程优化

以组合生物合成技术得到的基因工程FR-008／杀念菌素脱羧衍生物CS103为研究对象，在摇瓶水平进行培养条件的初步优化。确定了接种量、接种时间、发酵过程pH、装液量等初步条件。对3.7L发酵罐水平的培养条件进行优化，确定了最适搅拌转速和通气量，并初步建立了补料分批发酵工艺。结果表明，接种时间30h、接种量为10％、控制pH6.5-7.0、搅拌转速450r／min、通气量200L／h，发酵过程维持发酵液残余葡萄糖浓度5g／L左右，在3.7L发酵罐基因工程FR-008／杀念菌素脱羧衍生物CS103产量达到99.87μg／ml。本研究为基因工程FR-008／杀念菌素工业化生产工艺提供了依据。     

竹黄化学成分的分离和结构鉴定

从真菌竹黄(Shiraia bambusicola)的子座中首次分离得到了5个单体化合物,经UV、IR、~1H-NMR,~(13)C—NMR、MS及理化方法等确定了其结构。其中3个为苝醌类(perylene quinone)化合物。分别为竹红菌甲素、竹红菌乙素和六孢素.另2个分别为硬脂酸乙脂和硬脂酸。     

竹红菌素光化疗法治疗瘢痕疙瘩——217例临床疗效观察

我们自1979年4月至1983年4月对217例肥厚性瘢痕疙瘩用竹红菌素的光化疗法进行治疗并观察了四年余。效果比较满意。现报告如下: 一临床研究 1 治疗方法:采用竹红菌素软膏薄涂于瘢痕上,然后加用400 w照明荧光高压汞灯照射30分钟,     

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.     

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.