S—腺苷甲硫氨酸合成酶及其在S—腺苷甲硫氨酸合成中的应用

S－腺苷甲硫氨酸（SAM）参与多种生化反应，是生物体内重要的中间代谢物，其制备方法有化学合成法，发酵法和酶促转化法3种，酶促转化法主要涉及S－腺苷甲硫氨酸合成酶，文章着重介绍了大肠杆菌，酵母和大鼠肝脏的SAM合成酶及其编码基因和SAM合成酶基因工程菌酶法转化生产SAM的研究。     

S-腺苷甲硫氨酸研究进展

综述一种重要代谢中间物质S－腺苷甲硫氨酸的体内代谢功能，制备，稳定化研究和临床应用进展。     

S—腺苷甲硫氨酸的临床及药理研究进展

综述一种重要的内源性物质S－腺苷甲硫氨酸及其代谢物的生化及药理作用,并对其临床用于治疗某些疾病的现状与前景进行了介绍。     

腺苷钴胺及其片剂的稳定性考察

考察了腺苷钴胺原料药及其片剂的长期稳定性。结果表明在避光条件下保存3a，原料药稳定，片剂稳定性降低，为该品的生产和贮存提供参考。     

注射用双黄连与13种常用药物配伍稳定性研究

对注射用双黄连与临床上常用的13种药物配伍的稳定性进行了研究。结果表明：苯唑青霉素，氨苄青霉素，维生素B6，三磷酸腺苷，三氮唑核苷，辅酶A，甲硝唑与双黄连配伍无显著性变化；双黄连与诺氟沙星，环丙沙星，氧氟沙星，维生素C，丁胺卡那霉素，氢化可的松则不宜配伍。     

MAT1A基因突变导致高甲硫氨酸血症四例临床与基因变异分析

<正>单纯性高甲硫氨酸血症是由于体内甲硫氨酸(Met)代谢过程受阻导致血甲硫氨酸增多的一种疾病,多呈常染色体隐形遗传,少数为常染色体显性遗传。该病多数由甲硫氨酸腺苷转移酶(MAT)缺陷所致,甘氨酸N-甲基转移酶(GNMT)和S-腺苷同型半胱氨酸水解酶(AHCY)缺乏也可导致高甲硫氨     

反相高效液相色谱法检测红霉素发酵过程中S-腺苷甲硫氨酸

建立用反相高效液相色谱（RP—HPLC）检测红霉索发酵液中S-腺苷甲硫氨酸（SAM）的方法，观察其在发酵过程中的变化。样品经离心、超声等处理，进行RP—HPLC分析，梯度洗脱。实验结果说明，该方法可以使SAM与发酵液中其它复杂组分得到较好的分离。红霉素发酵过程中SAM量随时间呈曲线变化，高峰值出现在96h左右。     

三磷酸腺苷二钠水溶液化学稳定性研究

本实验在广泛pH范围对三磷酸腺苷二钠化学稳定性进行了研究。测定了不同温度、不同pH的速度常数,按Arrhenius方程测得不同pH的分解活化能及不同温度下最稳定的pH。并证明柠檬酸根离子对三磷酸腺苷二钠水解反应有催化作用。     

三磷酸腺苷二钠水溶液化学稳定性研究

本实验在广泛pH范围对三磷酸腺苷二钠化学稳定性进行了研究。测定了不同温度、不同pH的速度常数,按Arrhenius方程测得不同pH的分解活化能及不同温度下最稳定的pH。并证明柠檬酸根离子对三磷酸腺苷二钠水解反应有催化作用。     

妊娠肝内胆汁淤积症76例分析

目的观察腺苷甲硫氨酸用于妊娠肝内胆汁淤积症(ICP)的疗效。方法将2005年1月至2011年1月确诊的76例ICP孕妇随机分为治疗组45例和对照组31例,两组孕妇均进行常规保肝治疗,治疗组在保肝治疗基础上加用腺苷甲硫氨酸治疗,对比观察两组治疗效果。结果治疗组皮肤瘙痒、黄疸、消化道症状减轻,血清甘胆酸水平、肝功能等指标下降,总有效率为93.3%,较对照组(80.6%)高,差异有统计学意义(P<0.05)。结论腺苷甲硫氨酸用于治疗ICP疗效确切,可促进内源性解毒过程中巯基的合成,发挥抗胆汁酸淤积作用。     

Selectivity of McN-A-343 in stimulating phosphoinositide hydrolysis mediated by M1 muscarinic receptors.

The potency and efficacy of McN-A-343 (McN) in stimulating phosphoinositide (PI) hydrolysis were investigated in Chinese hamster ovary cells transfected with the m1 and m3 muscarinic receptor genes, in comparison with carbamylcholine (CBC). In m1 cells, CBC and McN increased PI hydrolysis by 17- and 9-fold over basal, respectively, with corresponding EC50 values of 4.2 and 4.3 microM. Whereas the maximal stimulatory response to CBC was slightly less in m3 cells (11-fold over basal), McN elicited only up to a 2-fold increase in PI hydrolysis in these cells. Competition binding data with N-[3H]methylscopolamine showed that McN had a higher affinity in m1 than in m3 cells, whereas CBC did not differentiate well between the two receptor subtypes. The partial agonistic activity of McN was demonstrated by its ability to suppress the stimulation by CBC to its own maximal response in both cell lines in a dose-dependent manner and by its low efficacy and the absence of receptor spareness. The PI response to the full agonist CBC in m3 cells was associated with a larger receptor reserve than in m1 cells. Thus, differences in receptor spareness cannot account for the apparent selectivity of McN in activating m1 muscarinic receptors. Differences in the sensitivity of m1 and m3 cells to McN were not due to differences in receptor concentration, despite the fact that the receptor density in m1 cells was 2-fold higher than in m3 cells. Our results suggest an actual selectivity (but not necessarily specificity) of the effects of McN in increasing Pl hydrolysis mediated by M1 receptors.     

Verapamil-induced transmitter release in rat diaphragm muscle

Verapamil was examined for its effect on the frequency of miniature end-plate potential (m.e.p.p.) in rat diaphragm muscles. Verapamil (5 x 10(-5) M) raised the m.e.p.p. frequency. This effect was reversible, reproducible, and concentration dependent. The rise in the frequency was maintained in the presence of external Ca++ but was transient in the absence of external Ca++. Lowering the temperature to 20 degrees C slightly decreased the average frequency of m.e.p.p. in the normal medium. The effect of verapamil was also present at a low temperature but was delayed in its onset. The resting membrane potential of the muscle fiber was not affected by the agent. These results suggest the possibility that verapamil increases the transmitter release from motor nerve terminals, and the effect is possibly due to a release of Ca++ for its initiation, but is dependent on external Ca++ for its maintenance.     

Primary, secondary, and tertiary metabolite kinetics

Because of the propensity of nascently formed metabolites towards sequential metabolism within formation organs, theoretical and experimental treatments that achieve mass conservation must recognize the various sources contributing to primary, secondary, and tertiary metabolite formation. A simple one-compartment open model, with first-order conditions and the liver as the only organ of drug disappearance and metabolite formation, was used to illustrate the metabolism of a drug to its primary, secondary, and tertiary metabolites, encompassing the cascading effects of sequential metabolism. The concentration-time profiles of the drug and metabolites were examined for two routes of drug administration, oral and intravenous. Formation of the primary metabolite from drug in the gut lumen, with or without further absorption, and metabolite formation arising from first-pass metabolism of the drug and the primary metabolite during oral absorption were considered. Mass balance equations, incorporating modifications of the various absorption and conversion rate constants, were integrated to provide the explicit solutions. Simulations, with and without consideration of the sources of metabolite formation other than from its immediate precursor, were used to illustrate the expected differences in circulating metabolite concentrations. However, a simple relationship between the area under the curve of any metabolite, M, or [AUC (m)], its clearance [CL(m)], and route of drug administration was found. The drug dose, route, fraction absorbed into the portal circulation, Fabs, fraction available of drug from the liver, F, availabilities of the metabolites F(m) from formation organs, and CL(m) are determinants of the AUC(m)'s. After iv drug dosing, the area of any intermediary metabolites is determined by the iv drug dose divided by the (CL(m)/F(m] of that metabolite. When a terminal metabolite is not metabolized, its area under the curve becomes the iv dose of drug divided by the clearance of the terminal metabolite since the available fraction for this metabolite is unity. Similarly, after oral drug administration, when loss of drug in the gut lumen does not contribute to the appearance of metabolites systematically, the general solution for AUC(m) is the product of Fabs and oral drug dose divided by [CL(m)/F(m)]. A comparison of the area ratios of any metabolite after po and iv drug dosing, therefore, furnishes Fabs. When this fraction is divided into the overall systemic availability or Fsys, the drug availability from the first-pass organs, F, may be found.(ABSTRACT TRUNCATED AT 400 WORDS)     

ESI-Mass spectrometric and HPLC elucidation of a new ergot alkaloid from perennial ryegrass hay silage associated with bovine reproductive problems

This case report involves four dairies in the Willamette Valley, Oregon, which experienced reproductive problems associated with the presence of a large, previously unidentified, peak eluting at 5?min in a standard ergovaline high-performance liquid chromatography assay of perennial ryegrass silage fed to those animals. Mycotoxin analysis of the silage was negative, as was serological screening of the herds for infectious bovine rhinotracheitis, bovine diarrhea virus and Leptospirosis, including culturing of urine for Leptospira hardjo hardjobovis. Prolactin concentrations were low in most cattle, consistent with ingestion of ergot alkaloids. We believe that this peak represents a novel ergot alkaloid-related compound due to its extractability with Ergosil, its detectability due to fluorescence, and its chromatographic retention between ergovaline (mw?=?533) and ergotamine (mw?=?581). Its molecular weight was calculated as 570 owing to the predominance of a m/z 593.5 ion in the full scan ESI(+)MS and its deduced tendency to complex with Na(+) (as m/z 593) or K(+) (as m/z 609) ions. We offer rationales for elucidation of the structure of this compound, with the closest starting point comprising an m.w. of 566-a fructofuranosyl-(2-1)-O-beta-D-fructofuranoside derivative of 6,7-secoergoline from Claviceps fusiformis. This m.w. requires modifications, such as reduction of two double bonds in the secoergoline component to give the target 570 m.w. Despite the lack of a definitive structure, the analysis herein provides a starting point for eventual elucidation of this apparently new ergot alkaloid, and to guide and encourage further investigation as to its association with endophyte toxicosis in livestock.     

Technetium 99m Tc labeled lipoproteins. I. Preparation and evaluation of quality

Technetium 99m Tc labelled lipoproteins are novel diagnostic agents suitable for the study of the lipoprotein metabolism and prospectively for picturing the specific receptors. The paper reports the first results of the preparation and quality evaluation of very low density lipoproteins (VLDL) labelled with technetium 99m Tc. This radionuclide is, due to its advantageous properties, preferentially employed in nuclear medicine. The present paper resulted in a successful attempt to bind technetium 99m Tc to a lipoprotein carrier with selective transport and targeted organ-specific biodistribution.     

Antioxidant and free radical scavenging potential of Citrullus colocynthis (L.) Schrad. methanolic fruit extract

Citrullus colocynthis (L.) Schrad. (Cucurbitaceae) is a medicinal plant traditionally used as an abortifacient and to treat constipation, oedema, bacterial infections, cancer and diabetes. Preliminary phytochemical screening of the plant showed the presence of large amounts of phenolics and flavonoids. Subsequent quantification showed the presence of 0.74% (m/m) phenolics (calculated as gallic acid) and 0.13% (m/m) flavonoids calculated as catechin equivalents per 100 g of fresh mass. The presence of phenolic compounds prompted us to evaluate its antioxidant activity. In the present study, methanolic fruit extract of C. colocynthis was screened to evaluate its freeradical scavenging effect. The highest antioxidant and free radical scavenging ability of the fruit extract was observed at a concentration of 2500 microg mL(-1).     

运用回归分析法对心电图QT间期正常界限值快速估算的分析研究

传统的心电图ＱＴ间期正常界限值的计算方法较为繁琐，本文运用回归分析法推算出ＱＴ间期正常界限值：（３ｍ＋１８）／１００≤ＱＴ≤（ｎ＋２０）／１００（ｍ、ｎ分别为ＲＲ间期的中格数、小格数，ＱＴ间期单位为秒，适用范围为１２≤ｎ≤３０，ｍ＝ｎ／５），据此可进行快速估算，值得在临床心电图诊断中推广应用。     

Effect of metabolites of chlorpromazine on plasma prolactin levels in male rats

Since prolactin secretion is under vigorous dopaminergic inhibition, neuroleptic drugs can, because of their capacity to block dopamine receptors, produce large increases in plasma prolactin levels in man and laboratory animals. The capacity of intramuscular (i.m.) chlorpromazine and 6 of its metabolites to increase plasma prolactin levels in male rats was compared. 7-Hydroxychlorpromazine produced increases in plasma prolactin equivalent to those produced by chlorpormazine. The following metabolites had no effect on plasma prolactin levels after i.m. injections of 5 mg/kg: 8-hydroxychlorpromazine; 7, 8-dihydroxychlopromazine; 8-hydroxy-7-methoxychlorpromazine; 7-methoxychlorpromazine; and chlorpromazine sulfoxide. 8-Hydroxychlorpromazine, 7-methoxychlorpromazine, 7, 8-dihydroxychlorpromazine and chlorpromazine sulfoxide had no effect even after 25 mg/kg i.m. The capacity to increase rat plasma proclactin correlates highly with other methods of determining potential antipsychotic activity of chlorpromazine and its derivatives.     

A comparison of the binding characteristics of class I antiarrhythmic agents for human muscarinic m1-m3 receptors.

The binding characteristics of the class 1 antiarrhythmic agents, cibenzoline, disopyramide, disopyramide metabolite (the main active metabolite of disopyramide in humans), and pirmenol, for human muscarinic receptors (m1-m3) stably expressed in Chinese hamster ovary cells (CHO) were investigated by binding assay with [3H]N-methylscopolamine ([3H]NMS) as a ligand. All of these agents inhibited the specific [3H]NMS binding to membrane preparations in a concentration-dependent manner. The potencies of affinity of these agents for m1, m2, and m3 receptors (compared by IC50) were disopyramide > pirmenol > disopyramide metabolite > cibenzoline, pirmenol > cibenzoline > disopyramide > disopyramide metabolite, and disopyramide > disopyramide metabolite > pirmenol > cibenzoline, respectively. Some competition curves of cibenzoline, disopyramide, and pirmenol were shallow, and Hill coefficients of these curves differed from unity, suggesting that these agents have allosteric binding characteristics for human muscarinic receptors. The m2-selective ratios to m1 (IC50 m1/IC50 m2) and m3 (IC50 m3/IC50 m2) of cibenzoline were 4.0 and 16, and those of pirmenol were 6.5 and 43, respectively, whereas those of disopyramide and its metabolite ranged from 0.46 to 1.6, suggesting that cibenzoline and pirmenol exerted high selectivity to the m2 receptor. We conclude that (a) all class 1 antiarrhythmic agents in this study have inhibitory effects on human m1, m2, and m3 receptors, and some of those binding may show allosteric characterization; (b) disopyramide and its metabolite have similar affinity to m1 to m3 receptors; and (c) cibenzoline and pirmenol have high m2-selective ratios to m1 and m3.     

The effect of food and time of administration on the pharmacokinetic and pharmacodynamic profile of metrifonate.

OBJECTIVE: Metrifonate--via its pharmacologically active metabolite DDVP--is an inhibitor of cholinesterase effective in the treatment of Alzheimer's disease. Two separate studies were performed to investigate the influence of food and time of administration, respectively, on the concentration vs. time profiles of metrifonate and DDVP and cholinesterase inhibition. METHODS: In study I, a single dose of metrifonate 50 mg tablet was administered either in the fasting condition or within 5 min after completion of an American breakfast. In study II, a single dose of metrifonate 80 mg tablet was given either at 8:00 a.m. after overnight fasting, 7:00 p.m. (7 h after lunch) or 10:00 p.m. (4 h after dinner). Both studies were performed in a non-blind, randomized, single-centre, cross-over design in healthy Caucasian volunteers. AUC and Cmax of metrifonate and DDVP as primary parameters were compared between treatments by ANOVA and acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition vs. time profiles were assessed. RESULTS: In study I a high-fat/high-calorie breakfast had no effect on the AUC of DDVP, while its Cmax was decreased to 56% and tmax was prolonged, compared to the fasting condition. The effects on metrifonate were similar. In study II bioequivalence was shown for AUC and Cmax of DDVP when comparing administration of metrifonate at 8:00 a.m. and 7:00 p.m. Administration at 10:00 p.m. also had no effect on AUC of DDVP while a reduction in rate of absorption was observed. In both studies the equivalence in AUC of DDVP was paralleled by equivalent effects on BChE inhibition. Following single metrifonate administration little inhibition of AChE was observed. Metrifonate was well tolerated. CONCLUSIONS: Delayed gastric emptying is likely to cause the reduced rate of absorption of metrifonate with food. In view of unchanged bioavailability of its active metabolite, this food effect is considered to be without clinical relevance and metrifonate can be administered with or without food. The decrease in rate of absorption following administration of the drug at 10:00 p.m. is either a protracted food effect or an effect of time. As the bioavailability of DDVP as well as pharmacodynamic profiles were independent of the time of administration it is concluded that metrifonate can be taken in the morning or evening without compromising its safety or efficacy.