固态发酵产纳豆激酶的工艺优化

目的研究纳豆菌的固体发酵。方法采用单因素和正交试验 ,对以豆渣为原料纳豆菌固体发酵生产纳豆激酶的工艺条件进行了优化。结果固体发酵最佳条件为培养基配比豆渣∶麸皮 =5∶2 ,初始含水量 6 5 % (w) ,接种量 10 % (φ) ,初始pH 8 0 ,培养温度 35℃ ;采用最适培养基和优化工艺 ,在 2 5 0mL三角瓶中进行验证实验 ,纳豆激酶的酶活可达到 15 77U·g-1。结论以豆渣为原料固体发酵产纳豆激酶是可行的     

重组水蛭素Ⅲ的工程菌的培养及高密度发酵

为提高重组水蛭素Ⅲ工程菌的产水蛭素量，采用正交实验法确定了较佳培养基组分，优化了摇瓶发酵工艺和发酵条件，工程菌摇瓶水蛭素产量稳定在2000ATU／ml左右，30L发酵罐批式发酵水蛭素产量达到4000ATU／ml，补料一批式发酵水蛭素产量达到8000ATU／ml。     

海洋小单孢菌FIM02523产rakicidin B发酵工艺研究#br#

目的 提高海洋小单孢菌FIM02523发酵液中的生物活性成分rakicidin B含量。方法 采用单因素实验、正交设计实验等方法优化发酵培养基组成比例及培养条件。结果 确定了最优rakicidin B发酵培养基：可溶性淀粉4.0%,蔗糖1.0%,大豆蛋白胨1.0%,酵母粉2.0%,甘氨酸0.1%,NaCl 0.5%,MgSO4 0.05%,CaCO3 0.5%;最优摇瓶发酵条件：发酵周期为120h,接种量5.0%,500mL摇瓶装量100mL,摇床转速220r/min,发酵温度30℃,培养基初始pH值为7.5。结论 优化后发酵工艺rakicidin B的发酵效价较初始工艺提高了约7.3倍。     

麦考酚酸产生菌液体发酵条件的优化

研究了短密青霉菌L产生麦考酚酸的发酵工艺条件，包括斜面培养基种类、初始pH、培养温度、碳氮源种类等，并通过均匀设计法优化了发酵培养基的组成。在优化条件下，摇瓶发酵单位达8565μg／ml，比优化前提高了89％。     

地衣芽孢杆lw-72合成纤溶酶的摇瓶发酵工艺优化

通过单因素试验和正交试验确定地农芽孢杆菌lw-72摇瓶发酵合成纤溶酶的最佳条件,最佳培养基组成为:玉米粉0.5%、黄豆饼粉2.0%、Na_2HPO_4 0.4%、NaH_2PO_4 0.2%、CaCl_2·2H_2O 0.01%、KCI 0.01%;培养摹初始pH为7.0;最佳培养条件:装液量30 ml/250 ml摇瓶,接种量10%,发酵时间为72 h.在该条件下发酵液中纤溶酶酶活力为622 u/ml,是初始发酵培养基的3.4倍.     

霉酚酸产生菌短密青霉菌UA-32的发酵研究

研究短密青霉菌UA-32产生霉酚酸的发酵条件。改良了种子培养基,并对发酵所需的氨基酸、碳源进行了考察;采用正交设计优化得到发酵培养基配方。优化后的摇瓶发酵单位比优化前提高90%。     

水蛭素基因工程菌的培养

采用正交实验法优化了水蛭素基因工程菌的发酵培养基，得到较佳培养基配方及培养条件，并优化了发酵工艺，摇瓶培养22h，发酵液抗凝血酶活力可达850ATU/ml，25L发酵罐培养18h，发酵液中抗凝活力亦可达800ATU/ml，水蛭 素表达量在原有基础上有了大幅度提高，为大规模培养及工业生产建立了可行路线。     

氧载体正己烷对兽疫链球菌发酵生产透明质酸的影响

在摇瓶发酵过程中向培养基添加氧载体正己烷,考察其对兽疫链球菌发酵生产透明质酸的影响.结果显示,发酵5 h时添加0.5%正己烷,500 ml摇瓶装液量50 ml,37℃振荡(220 r/min)培养30 h,透明质酸产量为0.585 g/L,较不添加正己烷的对照提高了24.2%.     

水蛭素基因工程菌的培养条件优化

通过正交实验对水蛭素基因工程菌的发酵培养基进行了优化,并由此得到较佳培养基配方为玉米浆4.5%,牛肉膏2.5%,谷氨酸钠1.5%;以此优化培养基在初始PH6.5,种龄12小时和温度37℃等条件下,摇瓶发酵液水蛭素活力可达到1200ATU/ml.     

肝素酶的发酵工艺研究

优化了发酵培养肝素黄杆菌生产肝素酶的半合成培养基配方，种子液种龄48h，接种量10％，装量90ml／（750ml摇瓶），25℃培养32h。采用该优化方案，肝素酶的发酵水平可达1768u／L，较合成发酵培养基提高52％。     

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.     

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.     

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.