利福霉素SV发酵工艺优化的研究

本文通过对影响利福霉素SV发酵因素一温度、溶氧和补料方式的研究，得出结论：在控制培养温度28．5℃、溶氧25％以上的条件下，采用流加方式补料工艺，利福霉素SV的发酵效价较原工艺有明显提高，此工艺已在20T发酵罐上进行工业化生产，发酵效价比原生产工艺有较大提高。     

利福霉素B发酵放大I．从摇瓶到15L发酵罐的发酵放大

研究了溶氧和剪切力对地中海拟分枝酸菌XC－925发酵产生利福霉素B的影响，并对利福霉素B从摇瓶到15L发酵罐的发酵放大及15L发酵罐流加补料发酵进行了研究。利用摇瓶研究结果表明地中海拟分枝酸菌XC－925发酵产生利福霉素B时对溶氧要求较高，而对剪切力不太敏感。以溶氧为依据，在15L发酵罐间歇发酵过程中，控制溶氧不低于25％，利福霉素B的发酵效价可达到1000u/ml左右，发酵周期（6d）较摇瓶发酵缩短了1d。15L发酵罐如采用流加补料发酵工艺，利福霉素B的发酵效价还会有较大幅度提高。     

利福霉素B发酵放大Ⅰ.从摇瓶到15L发酵罐的发酵放大

研究了溶氧和剪切力对地中海拟分枝酸菌XC-925发酵产生利福霉素B的影响,并对利福霉素B从摇瓶到15L发酵罐的发酵放大及15L发酵罐流加补料发酵进行了研究.利用摇瓶研究结果表明地中海拟分枝酸菌XC-925发酵产生利福霉素B时对溶氧要求较高,而对剪切力不太敏感.以溶氧为依据,在15L发酵罐间歇发酵过程中,控制溶氧不低于25%,利福霉素B的发酵效价可达到10000u/ml左右,发酵周期(6d)较摇瓶发酵缩短了1d.15L发酵罐如采用流加补料发酵工艺,利福霉素B的发酵效价还会有较大幅度提高.     

利用均匀实验优化利福霉素SV发酵培养基氮源配比

应用均匀设计的方法对利福霉素SV发酵培养基中的氮源配比进行优化。研究了氮源中各成分对发酵效价的影响。确定各成分的最佳配比并用实验验证，使摇瓶发酵效价提高了10％以上。并对利福霉素SV产生菌在新、老培养基中的代谢特性进行了比较。     

利福霉素B发酵放大Ⅱ．从15L发酵罐到7m^3发酵罐和60m^3发酵罐流流加补料发酵放大

对利福霉素B从15L发酵罐到7m^3发酵罐和60m^3发酵罐流加补料发酵放大进行研究。采用单位体积所消耗的通气功能相同的放大原则，成功地将15L发酵罐流加补料发酵工艺放大到7m^3发酵罐和60m^3发酵罐，发酵效价分别达到17249u/ml和19110u/ml左右，60m^3发酵罐利福霉素B发酵生产水平已达到国际先进水平。     

利福霉素B发酵放大Ⅱ.从15L发酵罐到7m3发酵罐和60m3发酵罐流加补料发酵放大

对利福霉素B从15L发酵罐到7m3发酵罐和60m3发酵罐流加补料发酵放大进行研究.采用单位体积所消耗的通气功率相同的放大原则,成功地将15L发酵罐流加补料发酵工艺放大到7m3发酵罐和60m3发酵罐,发酵效价分别达到17249u/ml和19110u/ml左右.60m3发酵罐利福霉素B发酵生产水平已达到国际先进水平.     

盐霉素发酵工艺的优化研究

目的 优化盐霉素发酵工艺.方法 以白色链霉菌盐霉素-06-F2为产生菌,工艺条件为培养温度33℃,搅拌转速400 r/min,罐压0.05 Mpa,空气流量0.8 vvm,保证溶氧浓度40℅以上以及适当控制培养基中各成分含量.结果 与结论表明该工艺条件下发酵效价可以从61 400 U/ml提高到71 320 U/ml.     

利福霉素B的选育及其发酵的研究

目的：寻找新的菌种提高利福霉素B的发酵水平。方法：对菌株AmediterraneiXCl—02进行筛选、诱变,获得新的菌株。结果：获得高产菌株AmediterraneiXC9—25,生产能力较原始出发菌株AmediterraneiXCl—02提高1．385倍,效价达到10000u／ml。结论：通过工业方法产生菌株,并对其进行筛选变种是提高利福霉素B生产能力的有效途径。     

温湿氧环境程控化在微生物种子培养间的应用

阐述在利福霉素种子培养过程中控制湿度，温度，氧含量的必要性及其不同的阶段，怎样来控制温度，湿度，氧含量，以便提高利福霉素的发酵水平。     

格尔德霉素发酵工艺的优化

目的研究格尔德霉素产生菌吸水链霉菌SIPI.A.2039的发酵工艺,以提高产生菌生物合成格尔德霉素的能力。方法以本实验室保藏的吸水链霉菌SIPI.A.2039为出发菌株,从摇床转速、摇瓶装量、碳源、50L发酵罐参数等方面进行发酵工艺的优化研究。结果采用经过优化获得的发酵培养基和培养条件,发酵周期为144h时,格尔德霉素的摇瓶发酵效价可由原来的230μg/mL提高至2500μg/mL。在50L发酵罐中采用优化的溶解氧和补料工艺能够使格尔德霉素的发酵效价达到3700μg/mL,并使发酵周期比摇瓶缩短了48h。结论本实验得到的结果比国内外报道的格尔德霉素的发酵效价提高了两倍以上,该发酵工艺已经达到了产业化的要求。     

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.