药物对福氏志贺氏菌代谢抑制的微量热法研究

药物抑制细菌生长的热化学研究是当今热化学法研究的一个活跃领域．在这项研究中，Boling[1]、Nordmark[2]、屈松生[3]等人已做了不少有意义的工作．在前人工作的基础上，我们用热活性检测系统测定了福氏志贺氏菌属中五株细菌在药物抑制下生长的完整的热谱曲线．按指数生长模型计算出细菌代谢抑制下的生长速车常数，并用计算机拟会出生长速率常数与不同浓度药物之间的关系式，进一步得到生长速率常数为零（临界生长参数[4]）时的用药物浓度．此项研究工作的开展对于深入研究药物对细菌的抑制作用，筛选对某细菌抑制的特效药提供了一种新的…     

微量热法测定细菌的临界生长温度

应用微量热学的方法,我们已能成功地测得细菌生长过程的热谱,这种热谱包含着有关细菌生长代谢过程的丰富信息,例如对热谱曲线的指数生长段进行解析,可得出细菌生长的速率常数、激活能和有关的热力学参数。故采用微量热法测定细菌在不同培养温度下的生长速率常数,利用计算机拟合出相应k(速率常数)和T(培养温度)的线性关系式后,若把生长速率为零的温度定义为临界生长温度时,就可以根据由上述实验所得的k～T线性关系式求得细菌的临界生长温度。本工作仍采用微量热法对福氏志贺氏菌(S. flexneri)和大肠埃希氏菌(E. coli)进行实验测定。按文献的方法求出它们在不同温度下的生长速率常数;对于大肠埃希氏菌还用几种不同的培养基分别进行实验测定。     

环境气氛对微量热安瓿法测定细菌生长速率常数的干扰

采用微量热安瓿法测定细菌生长时,发现细菌的代谢产热曲线在第一指数生长期内出现了停留法没有报导过的显著分阶段现象,且在不同的阶段生长速率常数有很大差异,对药物抗菌性能的评估造成极大干扰.为了寻找此现象的可能原因,以具有代表性的兼性细菌大肠杆菌为例,设计了微量热安瓿法实验,考察了不同环境气氛下大肠杆菌的生长代谢产热;并模拟了停留法条件下细菌的生长环境,通过安瓿法测定了大肠杆菌的生长代谢产热,重新解析了这些条件下细菌的生长速率常数.结果表明环境气氛是造成此现象的主要可能因素,并为在不同环境气氛下采用微量热安瓿法准确评估细菌的生长速率提供了一个可参考的标准.     

微量热法表征邻香草醛氨基葡萄糖Schiff碱锌配合物的抗菌活性

用微量热法测定了大肠杆菌（细菌）及其在Ｚｎ－ｏ－ＶＧ（ｏ－ＶＧ：邻香草醛氨基葡萄糖Ｓｃｈｉｆｆ碱）作用下不同温度下的热谱；计算了它的生长速率常数ｋ、传找时间Ｇ、抑制率Ｉ、总产热量Ｑ、单个细菌的平均产热Ｑ０的单位时间平均每个细菌的产热量＾－量Ｑ０；建立了细菌生长代谢各种参量之间的函数关系，探讨了在不同温度和药物作用下细菌的生长代谢；发现可用ｔｇ、ｔｒ和ｔ表征细菌的生长代谢和药物的抗菌活性。     

Schiff碱药物对产气杆菌代谢抑制的热力学研究

用微量热法测定产气杆菌在不同温度条件下受到Schiff碱药物抑制的热谱曲线, 根据其指数生长期的热谱信息, 确定它在不同温度条件下的生长速率常数和反应活化能, 找出了该细菌的最佳生长温度。同时借用化学反应中的过渡态理论, 得到一系列热力学参数, 对细菌在受到抑制时的生长代谢进行了热力学分析。     

细菌生长的热动力学研究进展

本文简单介绍了绝热式和热导式量热计及理论模型,细菌生长的动力学模型,着重介绍了近五年中热动力学在研究细菌生长代谢过程中的应用;通过测定不同条件下细菌生长代谢过程的产热曲线,求得细菌生长代谢的热力学和动力学参数,研究细菌的生长条件和药物的抑制作用。     

人参对金黄色葡萄球菌的代谢过程促进作用的研究

前文[1]已报导了合成药物对细菌抑制作用的研究．药物抑菌生长的热化学研究是当今热化学法研究的一个活跃领域，Boling[2]、Nordmark[3]等人已做了很有意义的工作．在此基础上，作者对畜养药物促进细菌代谢过程进行了研究，用微量量热仪测定了人参对金黄色葡萄球菌代谢过程起促     

生物热动力学研究——大肠杆菌生长速率和激活能

大肠杆菌生长的全热谱已被测定,再进一步根据其指数生长期的热谱信息,确定了它的生长速率和激活能。在指数生长期,细菌数按指数规律增加,可用下式表示:n_t=n_0e~(kt)(1)式中:t为指数生长期开始后的某一时间,n_0,n_t分别为指数生长期开始时和t时的细菌数,k为生长速率常数。因此,同期细菌输出的热功率也是按指数规律同步增长。可表示为:     

基于微量热法和主成分分析的盐酸巴马汀抗白色念珠菌作用的研究

采用LKB-2277生物活性检测系统, 测定了37 ℃时白色念珠菌在巴马汀作用下生长代谢的热谱曲线, 并获得9个相应的定量热动力学参数, 经主成分分析综合评价巴马汀的抗白色念珠菌作用. 结果表明巴马汀的抗白色念珠菌作用主要受热谱曲线第二指数生长期的生长速率常数k2和最大产热功率 的影响, 通过分析这两个主要参数的数值变化, 能更方便、快捷和准确地评价巴马汀的抗白色念珠菌作用, 为进一步评价其它药物和化合物的抗菌作用提供了有用的方法和基础.     

硒和箬叶多糖对细菌生长代谢作用热化学特征研究

用微量热法研究了Na~2SeO~3和箬叶多糖对大肠杆菌和产气肠杆菌作用的热功率输出曲线,得到了大肠杆菌和产气肠杆菌在不同条件下的生长速率常数k等参数。结果表明:Na~2SeO~3在低浓度下对大肠杆菌生长有促进作用,在高浓度时对两种细菌均有很强的抑制作用,而箬叶多糖对大肠杆菌和产气肠杆菌生长代谢未表现出抑制作用。这为揭示硒的生物效应、进行药理学和毒理学等的研究、寻找高效低毒的新药提供了可靠的信息。     

氟喹诺酮类药物对大肠杆菌抑制作用量效关系的 热化学研究

用LKB-2277生物活性检测系统,测定了洛美沙星、诺氟沙星、培氟沙星三种氟喹诺酮类抗菌素在37℃时,对大肠杆菌的抑制作用过程的热效应变化。根据热动力学模型,拟合了药物的k～c,P~m~a~x～k,I%～c等关系,定量计算了药物的半抑制浓度Ic~5~0,从热动力学角度研究了氟喹诺酮类药物抗菌作用的量效关系,探讨了诺氟沙星和培氟沙星杀菌作用随着药物浓度增加呈双相变化的PE现象和作用机制。     

Pr3＋或La3＋与克拉红霉素对大肠杆菌的协同作用

用LKB-2277生物活性检测系统采用停流法于37 ℃测定了克拉红霉素及克拉红霉素分别与Pr(NO3)3和La(NO3)3混合后,对大肠杆菌生长抑制作用的热效应变化.根据热动力学模型进行了定量解析,得到了各体系的克拉红霉素浓度c与大肠杆菌生长速率常数k之间关系式及其半抑制浓度Ic50. 克拉红霉素:　　 k=0.03106－1.273×10－3c　Ic50=8.81 μg•mL－1　　(0.5～20 μg•mL－1) 克拉红霉素＋Pr3＋: k=0.02967－1.332×10－3c Ic50=7.38 μg•mL－1　　 (1～15 μg•mL－1) 克拉红霉素＋La3＋: k=0.02741－1.194×10－3c　Ic50=6.34 μg•mL－1　 (1～15 μg•mL－1) 微量热结果不仅表征了克拉红霉素的抗菌活性强于红霉素,Pr3＋或La3＋与克拉红霉素协同作用也使抗菌活性增强,而且反映了不同药物作用下细菌的生理、生化和代谢过程热动力学特征的变化.     

Some Pharmaceutical Properties of a New Branched Cyclodextrin, 6-O-α-(4-O- α-D-Glucuronyl)-D-glucosylβ-cyclodextrin

Some physicochemical and biological properties of a new branched cyclodextrin, 6-O--(4-O--d-glucuronyl)-d-glucosyl--cyclodextrin GUG--CyD) were investigated. Further, theinteraction of GUG--CyD with several drugs was studied by the solubility and spectroscopic methods, and compared with those of parent -CyD and 6-O--maltosyl--CyD(₂--CyD).The hemolytic activity of GUG--CyD on rabbit erythrocytes was lower than those of -CyD and ₂--CyD. GUG--CyD and ₂--CyD showed negligible cytotoxicity on Caco-2 cells up to at least 0.1 M. The inclusion ability of GUG--CyD to neutral and acidic drugs was comparable to or slightly smaller than those of -CyD and ₂--CyD, probably because of a steric hindrance of the branched sugar. On the other hand, GUG--CyD showed greater affinity for the basic drugs, compared with -CyD and ₂--CyD, owing to the electrostatic interaction of its carboxylate anion with positive charge of basic drugs. Thus GUG--CyD may be useful as a safe solubilizing agent particularly for basic drugs.     

微量热法研究硒代吗啉衍生物的抑菌作用

大肠杆菌;生长代谢;微量热法研究硒代吗啉衍生物的抑菌作用     

Affinity Capillary Electrophoresis Studies on the Influence of Alcohols on the Interaction of β-Cyclodextrin with Non-Steroidal Anti-Inflammatory Drugs

Summary The influences of methanol, ethanol, 1-propanol and 1-butanol on the binding constants of -cyclodextrin (-CD) with non-steroidal anti-inflammatory drugs such as acemetacin, indometacin, cinmetacin, sulindac and diclofenac sodium and the separation of these drugs were studied by affinity capillary electrophoresis. No obvious effect was observable upon addition of methanol up to 6% (v/v) in the running buffer, while the addition of other alcohols at the concentration of 2% resulted in obvious decrease in the binding constants of -CD with acemetacin, indometacin, cinmetacin and sulindac. With an increasing chain length of added alcohols, all of these changes increased. Upon additions of different alcohols in the running buffer the change of the binding constant of -CD with diclofenac sodium was inconspicuous. Based on these results, the separation conditions for these drugs were optimized. The presence of 6% methanol in the running buffer containing 3 mM -CD was helpful to the baseline separation of these drugs. The electrophorograms of these drugs in the presence of ethanol, 1-propanol and 1-butanol showed a worse separation due to the decrease in the binding constants. The methods for the separation of these drugs and the study on the binding constants possess the advantages of easy performance, high speed and low sample consumption. AcknowledgementThe authors gratefully acknowledge the financial support from the National Natural Science Foundation of China (No.20275017), the Science Foundation of Jiangsu (No.BS2001063) and the Key Project of Cancer Institute of Jiangsu Province.     

Method of kinetic analysis of photodegradation: nifedipine in solutions

A rate equation for photodegradation was derived from Lambert-Beer's law and Grotthus-Draper's law: -dc/dt=k1(1-exp(-(k2c+k3(c0-c))))k2c/(k2c+k3(c0-c)) where c is the concentration of reactant, c0 is the initial concentration of reactant, t is time, k1 is the rate constant, and k2 and k3 are the absorption coefficient of reactant and its photodegradation product, respectively. In a case where the photodegradation products have no photoabsorption, k3 assumes the value of zero in the above general equation. In a case where the photodegradation products have the same spectrum and molar absorptivity as that of the reactant, k3 assumes the value of k2, and hence the photodegradation is not a first-order reaction; however, the equation itself gives the pseudo-first-order reaction rate equation. In a case where the concentration of reactant is high enough, the equation approaches a zero-order reaction rate equation. The photodegradation rate of nifedipine in solutions under a germicidal lamp, near an ultraviolet fluorescent lamp and a fluorescent lamp was analyzed using the above equation. The photodegradation rate was directly proportional to the amount of light absorbed, and fitted well with the equation. The above theoretical equation was substantiated by the photodegradation of nifedipine, and hence is expected to apply to other photosensitive drugs.     

Stability of chosen beta-adrenolytic drugs of different polarity in basic environment

The stability of atenolol, acebutolol, and propranolol was investigated in sodium hydroxide solutions at concentrations of 0.1, 0.3, 0.5, and 1 M at 3 temperatures ranging from 37 to 95 degrees C. The degradation processes that occurred in drugs under investigation were described with kinetic parameters (k, t0.1, and t0.5) and energy of activation (Ea). It was found that the stability of the drugs increased toward lipophilic propranolol in the assumed experimental model. The rate constants k decreased, contrary to t0.1, t0.5, and Ea, which varied comparably to log P (partition coefficient), thus increasing from the most hydrophilic atenolol, through acebutolol of lower polarity, to the most lipophilic propranolol. The identification of degradation products was performed with the application of proton nuclear magnetic resonance spectrometry and thin-layer chromatography-densitometry and data from the literature.     

乌头类双酯型生物碱对嗜热四膜虫生长代谢的微量热学研究

建立灵敏表征乌头类双酯型生物碱(DDA)对嗜热四膜虫生长代谢影响的评价方法. 采用微量热法, 在不同给药条件下, 以表达功率-时间曲线(热谱曲线)的特征参数生长速率常数(k)、半数抑制浓度(IC₅₀)、最大输出功率(P_max)及达峰时间(t_p)和总产热量(Q_t)为指标, 对嗜热四膜虫生长代谢程度进行客观地量化评价. 结果表明, 随着3种DDA浓度的增加, 达峰时间t_p延长, 生长速率常数k、最大输出功率P_max等随之降低, 且生长速率常数k与相应的浓度间呈现良好的线性关系: r_乌头碱＝0.9910 (IC₅₀＝207.7 μg•mL^－1); r_新乌头碱＝0.9923 (IC₅₀＝412.5 μg•mL^－1); r_次乌头碱＝0.9977 (IC₅₀＝1497 μg•mL^－1). 同时由半抑制浓度IC₅₀得到3种DDA毒性的大小顺序: 乌头碱＞新乌头碱＞次乌头碱. 初步构效关系研究表明, 在化合物C(3)上引入羟基(OH)以及N原子上引入乙基(CH₂CH₃)均可明显增加双酯型生物碱对嗜热四膜虫的毒性作用.     

Microcalorimetric study of the effect of Benzoinum and Styrax on the growth of Escherichia coli

In this study, the effects of Benzoinum and Styrax on Escherichia coli (E. coli) growth were investigated by microcalorimetry. Using a TAM Air Isothermal Calorimeter, ampoule method, the power-time curves of E. coli growth at 37°C affected by Benzoinum and Styrax were measured. By analysing some quantitative thermokinetic parameters, such as growth rate constants k, the maximum heat-out power Pm, the time of the maximum heat-out power tm, the total heat production Qt and inhibitory ratio I, one could find that low concentrations (0-3.9 mg mL(-1)) of Benzoinum and Styrax had stimulation effects on E. coli growth, and high concentrations (7.8-125.0 mg mL(-1)) of these two drugs would inhibit the growth of the bacteria. The antibacterial effects of Benzoinum and Styrax can also be expressed as half inhibitory concentration IC50. The IC50 values for Benzoinum and Styrax are 78.5 and 88.0 mg mL(-1), respectively, which suggests that the antibacterial effect of Benzoinum on E. coli was much stronger than that of Styrax. This study provides a useful method to investigate the effects of herbal medicines on microbes. It also supplies some references for the application of Benzoinum and Styrax in clinical treatment.     

Activity of ginsenoside Rh<Subscript>2</Subscript> on the growth of mice splenic lymphocytes investigated by microcalorimetry and factor analysis

The power–time curves of mice splenic lymphocytes growth at 37 °C affected by ginsenoside Rh₂ were determined by microcalorimetry using a 3114/3236 TAM air bioactivity monitor with ampoule mode. Then, the minimal inhibitory concentration (MIC) of Rh₂ on splenic lymphocytes growth was determined by serial dilution method. From factor analysis (FA) on six quantitative thermokinetic parameters from the power–time curves, the activity of Rh₂ on splenic lymphocytes could be quickly evaluated by analyzing the changes in the two main parameters: growth rate constant k, and maximum heat-output power, P _m. The results showed that Rh₂ had strong inhibitory activity on splenic lymphocytes growth, and this inhibitory activity was strengthened with increasing concentration of Rh₂ in the concentration range of 1.0–32.0 μg mL⁻¹. This strong inhibitory also could be confirmed from the MIC of 50.0 μg mL⁻¹ of Rh₂ on splenic lymphocytes growth in RPMI-1640 culture medium. This study illustrated that microcalorimetry could not only offer a useful method for evaluating the activity of drugs, but also serve as a quantitative, sensitive, and simple analytic tool for the evaluation of drugs on cell growth.