搅拌对顶头孢霉丝形态和头孢菌素C生物合成的影响

搅拌能充分混合物料，增强氧的传递，但搅拌强度过强会影响工业生产菌的菌丝形态和产物生成。在头孢菌素C的发酵生产过程中，菌丝形态与产素的关系密切，通过采用显微图像定量分析技术，计算菌丝总长度和菌丝平均生长单位，表明过高的搅拌速度会打断菌丝，造成机械损伤．明显降低产率。更换80m^3生产罐搅拌桨之后，降低了剪切作用，大罐的发酵效价提高了33．3％，达到22926．8μg／ml。     

庆大霉素产生菌绛红色小单孢菌发酵过程中菌丝形态变化的电镜观察

本文对庆大霉素产生菌绛红色小单孢菌发酵过程中的菌丝进行了电镜观察。初步报告了它的超微特征,并提出了菌丝衰老和自溶的电镜参考指标。观察发现,小单孢菌菌丝的形态结构随发酵时间的增加而呈动态变化。生长繁殖旺盛的菌丝较粗,电子密度深,分布均一,衰老菌丝的一个明显指标是电子密度变浅,菌丝内出现斑点状电子致密团;菌丝出现断裂、分节,可能系自溶开始的特征,可以作为停止发酵的一个参考指标。     

绛红色小单孢菌丝和孢子诱变效应的比较

本文报道庆大霉素产生菌绛红色小单孢菌丝和孢子诱变效应比较。初筛用试管发酵代替摇瓶发酵,发酵液纸层折生物显影法测定庆大霉素产量和组份的变化。结果说明用菌丝诱变效果比用孢子诱变效果好,初筛到产生庆大霉素C_1为主的突变型和产生小诺霉素和C_1a的突变型。上述诱变型。上述诱变和初筛方法用于提高小诺霉素的产量也有较好的结果。     

青霉素菌株（ZPC—1）种子罐发酵工艺的优化

在采用种子罐和发酵罐二级发酵工艺生产过程中 ,由于种子罐装量系数较高 ,故移种时种子液无法被培养基有效地稀释 ,导致粘度高、移种时间长、菌丝长时间缺氧 ,极大地影响了菌丝的生长繁殖以及青霉素发酵生产。为有效地降低种子液的粘度 ,缩短移种时间 ,我们对种子罐发酵工艺进行了优化。种子液为非牛顿液体 ,粘度主要取决于种子液的物质组成和菌丝形态 [1] 。而种子液的物质组成取决于工艺 ,难以进一步优化。故只有通过有效地控制菌丝形态来降低种子液的粘度。我们通过优化搅拌工艺和通气工艺 ,控制了菌丝团直径 ,达到了降低种子液粘度和缩…     

青霉素生产的加工工程学的研究

作者在7l和24l发酵罐中,用二株青霉菌研究了青霉素发酵过程中的搅拌叶的形式和转速、剪切强度、菌丝形态、粘度等与氧的传递和抗生素生产能力之间的复杂关系。具有螺旋桨搅拌叶和内循环装置的24l发酵罐,搅拌转速为700rpm时,氧的传递受到限制,培养液中氧的相对饱和度为5%,H613菌株的青霉素生产水平只有0.4g/l;而在1500rpm时,氧的相对饱和度可达30～50%。高的氧分压能促进细胞的生长和青霉素的合成速率。但是过高的氧分压与剪切力能缩短生命周期及青霉素分泌期;同时还促进了其他途径的代谢,使原来可以用作合成     

抗生素西索米星发酵过程中次要组分的调控

在西索米星产生菌橄榄星孢小单孢菌Ｍ－４１的发酵代谢与产物合成的研究中,发现通过控制种子期菌丝的生长形态、培养基中磷酸盐含量,并在发酵过程中添加合适的抑制剂,可有效地减少发酵液中次要组分ｖｅｒｄａｍｉｃｉｎ的生物合成,增加主要组分西索米星的含量。     

不同实验条件对庆大霉素C组分含量的影响

庆大霉素是由绛红色小单孢菌和棘状小单孢菌发酵产生的氨基苷类抗生素。《中国药典》1995年版采用高效液相色谱法测定,用面积归一法计算硫酸庆大霉素C组分的含量。我们在执行此方法的过程中发现在不同的实验条件下,结果重现性较差,误差达3％以上。本文通过抽样五批,分别在市药检所、市第六制药厂实验室测定,分析峰面积归一法计算C组分含量误差原因。1 材料与方法1.1 仪器 均为SP8810型高效液相色谱仪。1.2 条件 色谱条件与系统适用性试验均符合《中国药典》     

绛红色小单孢菌发酵过程中细胞形态结构变化

对庆大霉素产生菌－绛红色小单孢菌发酵中细胞形态、结构变化进行了研究。扫描电镜观察，发现生长期细胞表面满微小颗粒，生产期则形成较大突起。诱射电镜观察到不同培养期细胞膜、细胞壁、细胞质、核区等超微结构都有明显变化。     

棘孢小单孢突变型菌株产生相模湾霉素的研究——Ⅰ.棘孢小单孢菌JIM-401变株的鉴定

对我国庆大霉素产生菌进行诱变育种时获得一变异株JIM-401,经形态、培养特征和生理生化等方面的研究表明,该菌株与原出发菌株——棘孢小单孢菌种相似;但在某些特性方面有较大的差异,故定名为棘孢小单孢菌JIM-401变株(Micromonospora echinospira JIM-401),它产生的抗生素主要组份为相模湾霉素和庆大霉素C_(1a)。     

紫外分光光度法快速测定庆大霉素含量在优化培养基中的应用

目的 在庆大霉素发酵培养基优化过程中,探索庆大霉素含量的快速测定方法.方法 以紫外分光光度法作为庆大霉素含量测定手段,采用正交试验方法,对紫色小单孢菌产庆大霉素的发酵培养基及发酵条件进行优化.结果 通过统计学分析,确定发酵培养基最优组合为:黄豆饼粉3.5%,CaCO,0.5%,淀粉5.5%,CoCl20.0006%.优化的发酵条件为:种龄60h,接种量12mL,装液量50mL/500mL摇瓶.在此优化条件下添加一定量的氨基酸培养6d,庆大霉素效价较优化前提高了85.5%.结论 本文用紫外分光光度法与微生物法测定庆大霉素发酵液效价产生的误差小于4%,该方法可以用于庆大霉素液体发酵培养基优化的快速筛选.     

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.