The influence of changes in extracellular and intracellular sodium concentration on detrusor contractility

OBJECTIVE: To determine the role of Na+-Ca2+ exchange in the regulation of isolated detrusor smooth muscle contractility. MATERIALS AND METHODS: Isolated guinea-pig detrusor strips were used to record isometric tension generated by; (a) electrical-field stimulation to elicit nerve-mediated responses; and (b) adding carbachol or superfusing with a high-K+ solution. The [Na+] gradient between extracellular and intracellular compartments was altered by: (i) reducing superfusate [Na+] in stages from 140.2 to 10.2 mm; (ii) addition of the cardiac glycoside strophanthidin (200 microm). RESULTS Reducing extracellular [Na+] reversibly reduced the magnitude of nerve-mediated contractions but increased the resting tension and magnitude of carbachol-induced contracture. The mean (sd) [Na+] required for a half-maximum effect on attenuating contractions, at 85.9 (6.2) mm, and developing contracture, at 59.1 (14.3) mm, were significantly different. The time constants of changes to nerve-mediated contractions and carbachol contracture were also significantly different, at 147 (5) vs 1207 (386) s, respectively. These differences suggest that separate mechanisms influence nerve-mediated contraction and contracture in low-Na+ solutions. Exposure to the cardiac glycoside strophanthidin produced a similar effect to low-Na+ solutions for carbachol contracture. Low-Na+ solutions had no significant effect on contractures induced by high extracellular [K+]. CONCLUSION Reducing the transmembrane [Na+] difference increases intracellular [Ca2+]. This increase is largely accommodated in intracellular stores, that can be released by exogenous carbachol. The results are consistent with the presence of a functional Na+-Ca2+ exchanger in the surface membrane. The lack of effect of low-Na+ solutions on contractures evoked by membrane depolarization is consistent with this conclusion. The reduction of the nerve-mediated contraction by low-Na+ solution might result from blockade of the nerve action potential.     

Reversible inhibition of (Na+ + K+)-ATPase with a cardiac glycoside.

The effect of a semisynthetic cardiac glycoside, Actinogen (Ay22241), on Na+ + K+ - ATPase was studied. Ay22241 was found to be as an effective inhibitor of the enzyme as ouabain, Ay22241 inhibition was a time dependent process and was completely reversible. While ouabain inhibition was also time dependent, it was only partially reversible. This reversibility with Ay22241 should make it a useful tool in studying the mode of action of cardiac glycosides.     

氧杂蒽酮类衍生物的合成

本文合成了14个1,3-二羟基氧杂蒽酮衍生物(Ⅱ～Ⅴ,Ⅷ,Ⅸ)。1,3-二羟基氧杂蒽酮与环氧氯丙烷在哌啶存在下反应,产生化合物(Ⅲ)及(Ⅳ)。(Ⅳ)与胺反应可得化合物(Ⅴ)。大鼠被动皮肤过敏试验(PCA)表明化合物(Ⅱ_c)有63%的保护作用(5 mg/kg静脉注射)。     

Determination of kava lactones and flavonoid glycoside in Scorzonera austriaca by capillary zone electrophoresis

A capillary zone electrophoretic method has been developed for the quantitative analysis of three active comppounds, 12-hydroxy-desmethoxyyangonin (HD), 12-beta-d-glucopyranoside-desmethoxyyangonin (GD) and luteolin 3'-(6-E-p-coumaroyl-beta-d-glucopyranoside) (LG) in Scorzonera austriaca with UV detection at 254 nm. The applied voltage was 25 kV and the capillary temperature was kept constant at 25 degrees C. The effect of buffer pH, the concentration of electrolyte and organic modifier on migration were studied systematically. Optimum separation was achieved with 20 mM borate buffer at pH 10.00 containing 10% (v/v) methanol. Daphnetin was used as internal standard for quantification. Regression equations revealed good linear relationship between the ratios of the peak area of each compound and its the ratios of concentration. All the correlation coefficients were higher than 0.9990. The relative standard deviations of migration time and the peak area were <1.46% and 5.13% (inter-day), and <1.65% and 5.16% (intra-day), respectively. The contents of the three compounds in S. austriaca were successfully determined with satisfactory repeatability and recovery.     

A phenylpropanoid glycoside with antioxidant activity from picria tel-ferae

A phytochemical study on Picria tel-ferae resulted in the isolation of a phenylpropanoid glycoside (1), which was reported for the first time from this plant. The structure of compound 1 was identified as 1-O-3,4-(dihydroxyphenyl)- ethyl-beta-D- apiofuranosyl- (1-->4)-alpha-L-rharmnopyranosyl- (1-->3)-4-O-caffeoyl- beta-D-glucopyranoside on the basis of spectroscopic analyses. In addition, it was found that 1 exhibited a remarkable inhibitory effect on lipid peroxidation initiated by either a free radical [AAPH; 2,2'-azobis-(2-amidinopropane)dihydrochloride] or generated hydroxyl radical (Fe2+/ascorbate). These findings, together with those of previous studies, suggest that P. tel-ferae possesses abundant phenylpropanoid glycosides, and the plant might be used beneficially in the treatment of oxidative stress-related human diseases.     

正交试验优选制首乌水煎煮工艺

目的优选制首乌最佳水煎煮工艺。方法以制首乌的代表成分2,3,5,4′-四羟基-二苯乙烯-2-O-β-D-葡萄糖苷为评价指标,采用L9（34）正交试验设计、高效液相色谱法考察药材粒度、浸泡时间、煎煮时间、煎煮次数四个因素,对制首乌的水煎煮工艺进行优选。结果最佳水煎煮工艺：粒度为小块,浸泡30 min,煎煮时间70min,煎煮次数3次。结论优选所得的最佳煎煮工艺科学合理。     

Cell wall active antifungal agents

The recent American approval of Cancidas^?, a semi-synthetic echinocandin, for salvage treatment of aspergillosis has demonstrated that the cell wall is a clinically viable target for treating fungal infections. Recently, a variety of new, sulfated members of the echinocandin lipopeptide family have been reported, which, like other echinocandins, are glucan synthesis inhibitors. In addition, two new classes of lipopeptide glucan synthesis inhibitors, the aerothricin lipopeptidolactones and the Sankyo lipopeptides, have been identified, as well as a novel member of the papulacandin family of liposaccharide glucan synthesis inhibitors. The first new structural class of glucan synthesis inhibitors discovered in over 20 years, the so-called sterol glycosides, is reviewed. Five different structural types within this class have been characterised. Finally, several novel compounds with cell wall antifungal activity based on inhibition of chitin synthase are reviewed.     

Digitoxin as an anticancer agent with selectivity for cancer cells: possible mechanisms involved

Accumulating preclinical and clinical data suggest that the cardiac drug digitoxin might be used in cancer therapy. Recent reports have shown that digitoxin can inhibit the growth and induce apoptosis in cancer cells at concentrations commonly found in the plasma of cardiac patients treated with this drug. Several mechanisms have been associated with the anticancer activity of digitoxin, yet at present it is unknown why malignant cells are more susceptible to this cardiac glycoside than non-malignant cells. This report analyses the possible anticancer mechanisms of digitoxin and proposes that the inhibition of glycolysis may be a key mechanism by which this natural product selectively targets cancer cells. Finally, whether or not there is enough evidence to support the clinical evaluation of digitoxin in patients with cancer is discussed.     

New xanthone glycosides from Securidaca inappendiculata

Three new xanthone glycosides, securixanside A ( 1 ), securixanside B ( 2 ), and securixanside C ( 3 ) were isolated from the stems of Securidaca inappendiculata . These compounds were characterized by spectrometric and chemical methods, including FABMS and one- and two-dimensional NMR experiments.     

Chemical constituents from Eupatorium chinense

Two new monoterpenoid glycosides, α-(E)-acaridiol 8-O-β-d-glucopyranoside (1) and α-(E)-acaridiol 9-O-β-d-glucopyranoside (2), as well as a new thiophen, 2-acetyl-3-hydroxy-5-(prop-1-ynyl)thiophen 3-O-β-d-glucopyranoside (3), were isolated from the roots of Eupatorium chinense. Their structures were determined on the basis of extensive spectroscopic and chemical analyses.