Choleresis and hepatic transport mechanisms

Summary To investigate binding of drugs to biliary micelles as a possible factor in the hepatic transport process, interaction of two uncharged compounds, ³H-ouabain and ³H-K-strophanthoside with biliary micelles was studied by ultracentrifugation of bile. The various bile acids normally present in rat bile were predominantly associated with cholesterol containing micelles, but not to the same extent. The tendency of the bile salts to be associated with mixed micelles was the greatest for conjugated chenodeoxycholate, somewhat lower for conjugated deoxycholate and the least for conjugated cholate. The sedimentation patterns of the water-soluble cardiac glycosides, added in vitro, indicated binding to mixed biliary micelles as well as non-cholesterol containing micelles. Also mannitol, a drug used to estimate canalicular bile flow, was found to be associated with both categories of biliary micelles.In spite of the binding of cardiac glycosides to the micelles, administration of taurocholate, which promotes formation of biliary micelles, did not stimulate biliary output of both glycosides. Also administration of the choleretics dehydrocholate and ethacrynic acid failed to enhance biliary output of the glycosides.These results indicate, that binding of drugs to biliary micelles diminishes the free concentration of drugs in bile and confirms earlier studies with organic anions that binding to biliary micelles is not a pertinent factor in the rate of biliary excretion.     

THE EFFECTS OF THYROID STATUS ON DIGOXIN DISTRIBUTION IN THE RAT

1. Tritiated digoxin was injected intravenously into euthyroid, hyperthyroid and hypothyroid rats. The rats were killed at intervals up to 24 h and tritium in serum and tissues counted. 2. Serum concentrations of tritium in the hyperthyroid animals were less than in the control group, whereas the concentrations in the hypothyroid group were similar to those in the control group. 3. Cardiac tissue concentrations of tritium were higher in the hyperthyroid group than in the control group, but in the hypothyroid group were similar to the control group. 4. The decreased serum levels in the hyperthyroid rats were probably due to an increased volume of distribution. 5. Pharmacological resistance to digoxin in hyperthyroidism must be due to some alteration in cardiac function and it is suggested that this is an increase in Na/K ATPase receptors.     

Comparative observation on the effects of Radix Tripterygium hypoglaucum tablet and Tripterygium glycosides tablet in treating erosive oral lichen planus

From2002to2003,94patientswitherosiveorallichenplanus(EOLP)weretreatedbydivid ingthemintotwogroups,receivingRadixTripterygiumhypoglaucumtablet(THT)or Tripterygiumglycosidestablet(TGT),respec tively.Theresultswerereportedasfollows. METHODS ClinicalMaterialsForacceptanceintothestudy,enrolledpa tientswerediagnosedwithEOLP,accordingtothediagnosticstandardissuedinthe Periodontal Diseases"(1)andconfirmedbypathologicalexami nation.Patientswerealsoexcludediftheyhadre ceivedpriorsystematic…     

A Comparison of the Inhibition by Cardiac Glycosides of the Isolated Intestine from the Rat and the Guinea Pig

A method described by Bieltvedt & Briseid (1966) and Bieltvedt (1967) for the determination of the inhibition by cardiac glycosides of the isolated, histamine-stimulated guinea pig ileum was modified to estimate the inhibition of the acetylcholine-stimulated rat jejunum. The glycoside concentrations causing 50 % inhibition of submaximal, isotonic contractions were determined, and the procedure was based on 20-minute contact periods between the muscle preparations and the cardioactive substances, and then 22-minute equilibration periods with chemical stimulation. The degree of inhibition was found to depend on the potassium content of the Tyrode solutions used. In a low potassium Tyrode solution (1.8 mM) the inhibition of the rat intestine by cardiac glycosides was found to be of the same order of magnitude as the inhibition of the guinea pig intestine. When the potassium chloride concentration was increased to 2.7 mM, the well known species difference was observed, the concentration of cardiac glycoside required for inhibition of the rat intestine being about 30 times higher than that required for inhibition of the guinea pig intestine. The range of potency of the different cardiac glycosides and aglycones which were tested in the low potassium. Tyrode solution, was the same for the two species. Presupposing an inhibition of Na⁺, K⁺-activated transport ATPases as the basic mechanism for the inhibition by cardiac glycosides of the isolated intestine preparations, a theory of qualitative differences between the transport enzymes in the two species is advanced. In the rat intestine the presence is suggested of one ATPase which is rather resistant to inhibition by cardiac glycosides, but sensitive to a reduction in potassium concentration, in addition to a glycoside-susceptible ATPase also present in the guinea pig intestine.     

Binding of Digitoxin and Digoxin to Normal Human β-Lipoproteins

Abstract The binding of digitoxin and digoxin to purified β-lipoprotein, obtained from pooled normal human serum, was studied under equilibrium conditions. Even with as high concentrations of unbound digitoxin or digoxin as 4 μmol/1 the preparations of β-lipoproteins, containing cholesterol 1.98–3.95 mmol/1, did not show any signs of saturation. The binding affinity of digitoxin was about ten times as high as that of digoxin. Gel filtration chromatography, performed on native serum after addition of ³H-digitoxin or ³H-digoxin, showed a minor fraction of the cardiac glycosides to be associated with the protein fraction of highest molecular weight. This phenomenon disappeared after precipitation of the β-lipoproteins. In clinical relations the contribution of protein bound digitoxin caused by the lipoprotein interaction is immaterial, in relation to that caused by the albumin interaction.     

Extracellular Ca2+ is obligatory for ouabain-induced potentiation of cardiac basal energy expenditure

1. The method of action of cardiac glycosides is commonly explained by the 'pump-inhibition hypothesis': inhibition of the Na+/K+-ATPase allows [Na+]i to rise, eventually reversing Na+/Ca2+ exchange. The resulting influx of Ca2+o increases [Ca2+]i, thereby activating intracellular Ca2+-dependent ATPases and, hence, energy demand. This sequence has been presumed to occur during diastole as well as systole. However, it has been reported that dihydro-ouabain-induced potentiation of heat production by quiescent ventricular trabeculae persists in the absence of Ca2+o. This implies that the pump-inhibition hypothesis is inapplicable during diastole. 2. We tested this implication by: (i). measuring the rate of oxygen consumption (Vo2) of arrested guinea-pig whole-hearts; (ii). measuring[Ca2+]i in quiescent ventricular trabeculae; and (iii). mathematical modelling using software (Oxsoft Heart, Oxford Software, Oxford, UK) based on DiFrancesco-Noble formalism. 3. Upon induction of arrest, whole heart Vo2 fell to one-quarter of its 'beating' value. Subsequent perfusion with ouabain (20 micromol/L), in the presence of Ca2+o, increased Vo2 fourfold. This increase was prevented by withholding Ca2+o. Comparable results were obtained in quiescent trabeculae: ouabain increased [Ca2+]i only if Ca2+o was present. Mathematical modelling readily simulated these experimental results. 4. We conclude that influx of Ca2+o is mandatory for potentiation of cardiac basal metabolism by cardiac glycosides.     

苁蓉总苷对正常小鼠学习记忆功能的影响研究

目的观察苁蓉总苷对正常小鼠学习记忆功能的影响。方法使用水迷宫实验、跳台法、避暗法重复2次检测正常小鼠学习记忆水平。结果2次实验结果显示苁蓉总苷可以明显降低水迷宫实验到达终点的时间,2min内到终点的动物数显著增多;可以使跳台的潜伏期明显延长,5min内的错误次数明显减少。结论苁蓉总苷可以提高正常小鼠的学习记忆功能。     

打顶对北柴胡皂苷类成分季节积累规律的研究

目的以总皂苷、柴胡皂苷a、c、d等多种成份为指标,确定柴胡的最佳采收期。方法采用HPLC法及分光光度法测定柴胡不同生长期的含量,并与植株的外观形态结合。结果不打顶柴胡从花期后不断上升,在绿果期的总皂苷含量最高,果实开始变为褐色时,总皂苷含量最低,大部分种子变为褐色时又略有升高;打顶柴胡总皂苷从花期后不断下降,在果实大部分变为褐色时含量又急剧升高,而后下降。柴胡不打顶和打顶对皂苷a、d的积累规律影响较小,柴胡皂苷a、d在花期含量最高,果实开始变为褐色时,含量达最低值,随种子的进一步成熟,皂苷a、d又略有升高。柴胡皂苷c含量在各个时期基本保持稳定。结论不打顶柴胡在8月末偶见个别果实变为黄色时,而打顶柴胡在9月中旬多数种子变为褐色时采收最佳。     

云南血竭中的三个配糖体

从云南‘雨林牌’血竭Ｄｒａｃａｅｎａ ｃｏｃｈｉｎｃｈｉｎｅｎｂｓｉｓ （Ｌｏｕｒ．）Ｓ．Ｃ．Ｃｈｅｎ中分离鉴定了一个新的酚苷：３,４－二羟基烯丙基苯４－Ｏ－「α－Ｌ－鼠李吡喃糖基（１→６）」－β－Ｄ葡萄吡喃糖苷,２个已知的甾体皂苷：２６－Ｏ－β－Ｄ－葡萄吡喃糖夫甾烷－５,２０（２２）,２５（２７）－三烯－１β,３β,２６－三醇－１－Ｏ－「α－Ｌ－鼠李吡喃糖基（１→２）－α－Ｌ－葡萄吡喃糖基－呋甾     

黔岭淫羊藿化学成分的研究Ⅰ

 目的:对黔岭淫羊藿(Epimedium leptorrhizumStearm.)的化学成分进行分离,并鉴定其化学结构?方法:采用柱层析方法进行分离,用UV,IR,MS,¹H-NMR和¹³C-NMR等光谱技术鉴定化合物的结构?结果:从醋酸乙酯部分分离到4个化合物,经鉴定为:thalictoside(Ⅰ),2″-鼠李糖基淫-羊藿次苷Ⅱ[2″-O-rhamnosyl-icarisidⅡ(Ⅱ)],箭藿苷A[sagitatosideA(Ⅲ)],大花淫羊藿苷B[ikarisosideB(Ⅳ)]?结论:化合物Ⅰ为苯酚苷类化合物,化合物Ⅱ,Ⅲ,Ⅳ为8-异戊烯基黄酮苷类化合物,4个化合物均为首次从该植物中分离得到?