金霉素链霉菌作为影响抗生素产量基因克隆的宿主

四环素(TC)和金霉素(CTC)产生菌金霉素链霉菌是重要的工业微生物,具有不同生产特性的金霉素链霉菌突变株可以作为四环素类抗生素生物合成基因克隆的宿主,也可用于以产生杂合抗生素为目标的实验,参与抗生素生物合成及抗性基因已在几株链霉菌中克隆。     

硫酸二乙酯和紫外线对金霉素链霉菌的诱变育种

考察了硫酸二乙酯 (DES)和紫外线 (UV)对金霉素链霉菌进行诱变的效果。其中 2 ?S诱变剂对金霉素链霉菌无明显的致死效应 ,但在含有金霉素 2 2 0 μg/ml的培养基上筛选结果表明 ,DES对金霉素产生菌产生了较强的诱变效果 ,菌株正突变率达 5 2 %。对金霉素链霉菌进行紫外诱变的结果表明 ,在营养贫瘠培养基上筛选的诱变效果较营养丰富培养基上的效果好 ,且遗传特性稳定。     

金霉素发酵过程的代谢特性及调控策略

利用金霉素链霉菌在50L自控发酵罐中发酵生产金霉素。分析了发酵过程的糖、氧、氮和磷的代谢特性以及菌体生长和金霉素生物合成的规律。结果表明，菌体前期的代谢控制显得非常重要，并对金霉素合成的整个过程起决定性作用。在参数相关理论的基础上，通过对发酵过程的实时优化，适宜增强前期的菌体生长，使物质代谢流有利于流向金霉素形成的途径，从而使金霉素的产率）效价）提高了10．3％。     

金霉素发酵工艺研究

金霉素产生菌金色链霉菌（Streptomces aureofaciens）9647经紫外线（253.7nm,30W,距离20cm,照射60s）照射、金霉素耐受等处理,得到一株金霉素突变株1-1-14,其摇瓶效价较出发菌株提高18%。采用流加补料工艺,金霉素的发酵效价较原工艺有明显提高,此工艺在100m3发酵罐中进行工业化生产,发酵效价比原生产工艺提高15%。     

金霉素链霉菌噬菌体的分布

金霉素链霉菌噬菌体的分布ＤｉｓｔｒｉｂｕｔｉｏｎｏｆｂａｃｔｅｒｉｏｐｈａｇｅｓｏｆＳｔｒｅｐｔｏｉｎｙｃｅｓａｕｒｅｏｆａｃｉｅｎｓ张菊英ＺｈａｎｇＪｕｙｉｎｇ（福州抗生素总厂，福州３５０００２）（ＦｕｚｈｏｕＡｎｔｉｂｉｏｔｉｃＧｅｎｅｒａｌＦａ...     

重离子束辐照诱变及高通量筛选金霉素高产菌株

应用不同剂量12C+6重离子束对金霉素链霉菌出发菌株B9-34-125进行辐照诱变,并应用96和48孔板高通量筛选金霉素高产菌株。结果表明：当重离子束12C+6离子的辐照剂量为60Gy时,对金霉素链霉菌的诱变效果显著,筛选出5株优势菌株,其中Z-1452菌株摇瓶发酵效价较对照提高14.4%,60m3发酵效价较对照提高5.7%,产量提高了2.6%。     

金霉素链霉菌抗噬菌体菌株的选育

从四环素产生菌金霉素链霉菌的异常发酵液中分离到几株噬菌体,对金霉素链霉菌进行了抗噬菌体选育,获得产量与对照水平接近的菌株,可用于生产。     

高效液相色谱法测定盐酸金霉素

在生产金霉素的生物工艺过程中,通常除主要是金霉素外,还含有少量的四环素、去甲基金霉素和差向异构体。这些组份用微生物检定法无法检测出,为能在生产工艺过程中或在盐酸成品中监测这些组份,必需运用高效液相色谱法。用HPLC法测定金霉素及相关的四环素类化合物近年虽有一些报道,但均无法同时测定金霉素(CTC)、四环素(TC)、去甲基金霉素(DMCTC)、4-差向金霉素(4ECTC)、4-差向四环素(4ETC),且分离效果不太理想。本文采用反相色谱分离技术,选择一定浓度的N,N二甲基甲酰胺的草酸溶液作为流动相,在波长365nm处测定,即可得到满意的分离效果,五个峰均有较好的对称性。利用此系统,可对盐酸金霉素工艺过程中及成品中的CTC、TC、DMCTC、4ECTC、4ETC作定量分析。     

去甲金霉素高产菌的选育及发酵培养基的优化

去甲金霉素产生菌金色链霉菌（Streptomces aureofaciens）1-28经60Co-r射线照射（剂量为30Gy）、去甲金霉素耐受等处理,得到一株去甲金霉素突变株2-16,其摇瓶效价较出发菌株提高32%。采用正交设计试验方法对该突变株的发酵培养基配方进行优化,得到最佳发酵培养基配方：猪油6.0%,棉籽粉4.0%,酪蛋白0.3%,硫酸铜0.06%。     

固定化金霉素产生菌原生质体使林可霉素转化的研究

用固定化金霉素产生菌（金霉素链霉菌，Ｓ．ａｕｒｅｏｆａｃｉｅｎｓ）的原生质体，在适当量的氯离子存在时，转化林可霉素生成抗菌活力比其本体高的产物。研究了反应时间、原生质体固定化浓度、填抖比、碳源、氮源、载体厚度、摇床转速和载体琼脂浓度等因素对转化反应的影响。经３２ｈ转化培养后，反应液抗菌活力最高可提高一倍以上。     

The synthesis of highly phosphorylated nucleotides, RNA and protein by Streptomyces aureofaciens.

During the sudden decrease in RNA synthesis in Streptomyces aureofaciens, i.e. around the 6th hour of cultivation, synthesis of adenosine and guanosine tetraphosphates and pentaphosphates begins. The synthesis of these nucleotides is highest during the onset of chlortetracycline production, around the 20th hour of cultivation and continues. During this phase of growth of S. aureofaciens, RNA and protein synthesis are reduced by about one order of magnitude as compared to the rate which can be observed at the beginning of cultivation, but the synthesis is not inhibited by exogenous CTC.     

Gastrointestinal absorption of inorganic mercuric compounds in vivo and in situ

The absorption of inorganic mercury in rats was studied by using ligated gastrointestinal segments and perfusion of small intestine. Poorly soluble mercuric oxide (HgO) as well as mercuric chloride (HgCl2) was absorbed from the ligated segments in the following order: duodenum greater than stomach = jejunum = ileum. The ligation of bile duct decreased the duodenal absorption of HgCl2, while no change was observed in that of HgO. In the bile duct-ligated rats, the coadministration of bile increased the absorption of HgCl2 compared to that in rats without the ligation. The absorption of HgCl2 was increased with an increase of pH of the solution perfused into small intestine. These results suggest that the alkalinity of bile promotes the absorption of HgCl2.     

UV-spectrophotometry study of membrane transport processes with a novel diffusion cell

A new system for prediction of drug absorption that takes into account drug dissolution and pH change in the gastro-intestinal tract was developed. In this new system, a drug (solid form) is added into a drug-dissolving vessel (pH 1.0) and the dissolved drug is transferred to a pH adjustment vessel (pH 6.0). Then the drug solution is transferred to the apical surface of Caco-2 cells, and the permeation rate of the drug across a Caco-2 monolayer is determined. This system was able to predict the oral absorption ratios of ten water-soluble drugs in humans. Using this system, it was predicted that drugs that permeated Caco-2 at a rate of more than 0.1% of the dose in 200 min would be almost completely absorbed after oral administration in humans. For a drug whose permeation ratio was less than 0.03%, the absorption ratio was predicted to be less than 30%. This system also enabled prediction of the absorption rate and variability in the absorption of albendazole, a drug with poor water solubility. It also enabled assessment of the improvement in absorption using a solid dispersion of albendazole-polymers that improved the water solubility. The results suggest that this system is useful for oral absorption screening of new drugs and pharmaceutical products.     

Clostridium perfringens epsilon toxin is absorbed from different intestinal segments of mice

Clostridium perfringens epsilon toxin is a potent toxin responsible for a rapidly fatal enterotoxaemia in several animal species. The pathogenesis of epsilon toxin includes toxicity to endothelial cells and neurons. Although epsilon toxin is absorbed from the gastrointestinal tract, the intestinal regions where the toxin is absorbed and the conditions favoring epsilon toxin absorption are unknown. The aim of this paper was to determine the toxicity of epsilon toxin absorbed from different gastrointestinal segments of mice and to evaluate the influence of the intestinal environment in the absorption of this toxin. Epsilon toxin diluted in one of several different saline solutions was surgically introduced into ligated stomach or intestinal segments of mice. Comparison of the toxicity of epsilon toxin injected in different sections of the gastrointestinal tract showed that this toxin can be absorbed from the small and the large intestine but not from the stomach of mice. The lethality of epsilon toxin was higher when this toxin was injected in the colon than in the small intestine. Low pH, and Na(+) and glucose added to the saline solution increased the toxicity of epsilon toxin injected into the small intestine. This study shows that absorption of epsilon toxin can occur in any intestinal segment of mice and that the physicochemical characteristics of the intestinal content can affect the absorption of this toxin.     

岩白菜素的大鼠在体肠吸收动力学

目的 研究岩白菜素在大鼠肠道中的吸收机理.方法 采用HPLC测定大鼠在体肠实验中岩白菜素的含量,从吸收部位、药物浓度、pH三方面研究岩白菜素在大鼠小肠中的吸收特性.结果 岩白菜素在全肠段均有吸收,但不同肠段的吸收存在差异.药物浓度和循环液的pH对吸收均有影响.结论 岩白菜素在大鼠肠道内吸收较少,吸收机制可能为被动扩散.     

Absorption of digoxin in man after oral and intrasigmoid administration studied by portal vein catheterization

Summary The absorption of digoxin has been studied in fasting patients undergoing transumbilical, portal catheterization for diagnostic purposes. A purely aqueous solution was administered orally in 4 patients and in the sigmoid colon in 2 patients. Blood samples were taken simultaneously from the portal and a peripheral vein. Plasma digoxin concentrations were determined by radioimmunoassay. Digoxin appeared early in the blood after oral administration; the average peak of porto-peripheral concentration differences was at 18 min. After intrasigmoid administration, absorption was slower, and no distinct peaks were found. Calculation of the mean amounts absorbed showed that half the dose had been absorbed via the portal vein during 2 hours in the oral study and during 6 hours in the intrasigmoid test. Approximately 2/3 of the dose had been absorbed during 6 hours after oral dosing. The absorption rate was estimated taking into account the decreasing amount of drug left to be absorbed at different times. After oral administration, the mean peak rate was found to correspond to an absorption half-time of 0.78 h, which was more than 20 times faster than the rate after 6 h. The mean peak rate after intrasigmoid administration appeared to be about 1/3 of that after oral dosing. Physiological factors that might account for these differences in absorption rate are discussed.     

Percutaneous absorption of piroxicam from ointment bases in rabbits

In order to investigate the process of percutaneous absorption from various ointment bases, the blood levels of piroxicam were determined at optimal intervals after the ointment application in rabbits.After the oral and intravenous administrations, the plasma levels of piroxicam were described by the two-compartment model. A pharmacokinetic model similar to the percutaneous absorption of indomethacin was developed to test the concepts regarding the percutaneous absorption of piroxicam from topical ointment bases.A reasonably good fit between experimental and calculated values was obtained by taking into account identical absorption rate constant (K_a) and the changes in drug release constant (K_r) and the fraction of drug absorbed (F).We found that piroxicam in the o/w ointment base (UCH ointment containing 12% propylene glycol) had a better percutaneous absorption effect than the other three different kinds of ointment bases which were a simple ointment, PEG ointment and petrolatum rosewater ointment.The pH value of the water phase in UCH ointment containing 12% propylene glycol was adjusted to pH 9.2 by the sodium bicarbonate-buffered solution, then the percutaneous absorption of piroxicam could be increased. The effect of the amount of piroxicam on the percutaneous absorption was also investigated.The optimal effect with the additives in the ointment was finally attained with an addition of 5% urea.     

The pharmacokinetics of chlortetracycline orally administered to turkeys: influence of citric acid and Pasteurella multocida infection

A physiologically based pharmacokinetic model was developed to describe the absorption and disposition of chlortetracyline (CTC) in the healthy and diseased (fowl cholera) turkey. The CTC was given (with and without citric acid) as an oral (15 mg/kg) or i.v. (1 mg/kg) dose. When minerals (0.3 g/L Ca2+, 0.1 g/L Mg2+) were dissolved in the bird's drinking water, the model indicated that the addition of citric acid (mass ratio of 10 citrate: 1 CTC) increased the fraction of dose absorbed from 0.06 to 0.16; once absorbed, the fractions of drug eliminated by renal excretion, biliary secretion, and chemical decomposition were 50, 46, and 4%, respectively. The presence of fowl cholera appeared to increase plasma levels by increasing the intestinal permeability and lowering the hepatic and/or renal clearance.