Choleresis and hepatic transport mechanisms

Summary To investigate, whether binding to micelles has a function in hepatic transport, biliary excretion of three organic anions, phenolphthalein-\-D-glucuronide (PG), dibromosulphthalein (DBSP) and indocyanine green (ICG) was studied in rats during saline, taurocholate or dehydrocholate administration. Taurocholate causes a weak choleresis with formation of biliary micelles, dehydrocholate a strong choleresis with little micelle formation. The two bile salts did not uniformly influence biliary excretion of the organic anions: biliary excretion of ICG (12.9 moles/kg) and DBSP (75.0 moles/kg) was stimulated by both bile salts: ICG excretion most pronounced by taurocholate and DBSP excretion most strongly by dehydrocholate. Biliary output of PG (25.8 and 200 moles/kg) was not stimulated by bile salt administration. Binding of PG, DBSP and ICG to biliary micelles was studied in sedimentation experiments by ultracentrifugation. PG, DBSP and ICG in bile showed a similar sedimentation pattern as ³H-taurocholate in bile, which indicates an association of all three anions with biliary micelles.Thus, the influence of bile salts on biliary transport of organic anions varies with the compound studied and the bile salt used, effects which cannot be explained by differences in binding to biliary micelles.The previously published paper of Vonk et al. (1974) is regarded as paper I in this series.     

Influence of spironolactone pretreatment on pharmacokinetics and metabolism of digitoxin in rats

Summary The influence of pretreatment with spironolactone (84 mg/kg at 3 days, twice per day) on the tritium levels in plasma, urine and feces of female SD-rats (n=9) was investigated at various time periods after oral administration of 25 g/kg ³H-digitoxin. In plasma, the concentrations of total radioactivity are reduced in pretreated animals to about 20% of tritium levels in control rats, while the half-life of radioactivity in both groups is almost identical, 2.9 days in pretreated rats and 2.8 days in controls. The lower plasma levels of tritium in pretreated rats coincide with a six-fold decrease in the urinary ³H-elimination and a corresponding increase in the fecal excretion. This is due to a higher biliary clearance of tritiated products in the early phase of elimination. The separation of the excretion products by TLC shows that spironolactone pretreatment enhances the splitting of the glycosidic bonds of digitoxin. The amount of digitoxigenin-bis-digitoxoside and of digitoxigenin-mono-digitoxoside excreted in urine and feces within 96 hrs is four and ten times greater than that recovered in control animals, respectively. The formation of the hydroxylation products digoxin and digoxigenin-bis-digitoxoside is decreased from 50% of the total excreted radioactivity in control to 15% in pretreated rats. The conjugation reactions with glucuronic and sulfuric acid are increased after pretreatment with spironolactone. Thus, the effect of spironolactone on digitoxin kinetics is apparently related to an enhancement of the hepatic excretory mechanism as well as to an enhanced metabolism.Supported by the Deutsche Forschungsgemeinschaft.     

改饮低氟水七年后氟骨症患者尿中六种元素排泄状况的研究

本文探讨了改饮低氟水７年后氟骨症患者尿中６种元素（Ｆ－、Ｃａ、Ｍｇ、Ｃｕ、Ｚｎ、Ｍｎ）的排泄状况。结果表明，改水７年后，氟骨症患者２４小时尿氟排泄量非常显著地高于非病区对照，尿钙排泄量显著地低于非病区对照，而尿镁、铜、锌、锰虽呈患者低于非病区对照的趋势，但无统计学上的差异。     

The role of intestinal microflora on daidzein excretion in urine in humans treated with chungpesagantang

This study examined the relationship between the metabolism of the constituents of herbal medicines by human intestinal microflora and the level of metabolites excreted in the urine. This was performed by administering Chungpesagantang (CST) to volunteers and measuring their fecal metabolic activity CST to and urine excretion of daidzein, one of the metabolite of CST The metabolic activity of of CST dadizein was 54.8 +/- 16.7 mmol/h/g wet feces. When CST was administered orally to the subjects, the amount of daidzein excreted in the urine over 24 h was 103.7 +/- 55.8 mg, which accounted for 20.2% of the puerarin, daidzin and daidzein contained in CST. However, neither puerarin nor daidzin were excreted in the urine. The profile of daidzein excreted in the urine was found to be in proportion to that of the metabolic activity of the CST components. This suggests that the daidzein level excreted in the urine of the subjects administered CST is associated with the daidzein glycoside-hydrolyzing activity of the fecal microflora.     

What do we (need to) know about the kinetic properties of nanoparticles in the body?

Nowadays the development and applications of nanotechnology are of major importance in both industrial and consumer areas. However, the knowledge on human exposure and possible toxicity of nanotechnology products is limited. To understand the mechanism of toxicity, thorough knowledge of the toxicokinetic properties of nanoparticles is warranted. There is a need for information on the absorption, distribution, metabolism and excretion (ADME) of nanoparticles and validated detection methods of these man-made nanoparticles. Determination of the ADME properties of nanoparticles requires specialised detection methods in different biological matrices (e.g. blood and organs). In this paper, the current knowledge on the kinetic properties of nanoparticles is reviewed. Moreover, knowledge gaps from a kinetic point of view (detection, dose, ADME processes) are identified.     

Tissue distribution and excretion of myosmine after i.v. administration to Long–Evans rats using quantitative whole-body autoradiography

Occurrence of the tobacco alkaloid myosmine has been proven in various staple foods, vegetables and fruits. Myosmine can be easily activated by nitrosation yielding 4-hydroxy-1-(3-pyridyl)-butanone (HPB) and the esophageal carcinogen N′-nitrosonornicotine. Most of the reaction products after myosmine peroxidation were also identified as urinary metabolites after oral administration to rats. Whole-body autoradiography with freeze dried or multiple solvent extracted tissue sections was used to trace [2′-¹⁴C]myosmine (0.1 mCi/kg bw) 0.1, 0.25, 1, 4 and 24 h after i.v. injection in Long–Evans rats. In addition, in vitro binding of radioactivity to esophageal and eye tissue was determined and excretion of radioactivity via urine and feces was quantified. Radioactivity is rapidly eliminated by renal excretion. Approximately 30% of the administered radioactivity was recovered in urine within the first 4 h and excretion with urine (72%) and feces (15%) was nearly complete after 24 h. A rapid concentration of radioactivity can be seen in the stomach and in the salivary and lachrymal glands. Rats killed 1 and 4 h after treatment showed by far the highest labeling in the accessory genital gland. High levels of nonextractable radioactivity were present in esophageal tissue and melanin. The half lives for the disappearance of radioactivity from various tissues are in the order of about 1 h. Eye and esophagus sections both showed nonextractable labeling after in vitro incubation with ¹⁴C-myosmine. In conclusion, the toxicological significance of myosmine accumulation in esophagus and accessory genital gland requires further investigations. Hair analysis might be applicable for myosmine biomonitoring, because of possible enrichment in melanin containing tissues.     

2型糖尿病周围神经病变与尿微量白蛋白排泄率相互关系研究

目的 分析2型糖尿病周围神经病变与尿微量白蛋白排泄率的关系.方法 收集我院2004年3月至今收治的150例糖尿病患者临床资料进行分析.结果 大量白蛋白组的感觉和运劝神经异常率显著较高.结论 糖尿病周围神经病变与尿微量白蛋白排泄率间存在密切的联系.     

Studies on the kinetics and renal excretion of low and high molecular weight dextrans in preterm babies,newborns and young infants

Administration of low and high molecular weight dextrans in the initial phase of shock is no longer controversial. The special conditions in newborns, however, have been insufficiently considered in planning therapy. This investigation aimed at determining the biological half-lives of dextran 40 (Rheomacrodex^®) and dextran 60 (Macrodex^®) in this age group. The half-life of dextran 40 was found to be 60 min and that of dextran 60 3 h. Preterm babies and newborns excrete up to 25% less dextran 40 and 60 in 24 h than infants and adults. Normal adult values for excretion are only reached towards the end of the first year of life.     

SARS恢复期患者血液与排泄物中SARS-CoV RNA的检测

目的应用巢式逆转录聚合酶链反应(RT—PCR)检测严重急性呼吸综合征(SAILS)恢复期患者血液与排泄物中的病毒RNA。方法对连续3次收集的23例确诊SARS恢复期(病程≥21天)患者的血、尿、痰、粪便标本进行核酸提取，设计特异性内外引物，使用巢式RT—PcR的方法进行病毒RNA检测。结果通过巢式RT—PCR，共检测到6份阳性标本，其中粪便标本中检测到4份，检出率为5．8％；痰标本中检测到2份，检出率为2．9％。在尿液和血液标本中未检测到病毒．RNA。结论个别SARS恢复期患者排泄物中有SARS病毒RNA存在，因此对恢复期患者的排泄物应慎重处理，对其引起SARS的再次传播的危险性需要进一步评估。     

Autonomous response of dog kidney to increased blood pressure with and without saline loading

Summary Isolated dog kidneys respond to high blood pressure by increased water and sodium excretion, as a result of both increased filtration and reduced fractional reabsorption. A saline load added in vitro to the blood is excreted quantitatively; the relation between blood concentration and saline excretion is not disrupted by hypertension, despite higher basal excretion; renal response to dilution factors is not altered; however, quantitative excretion of extra saline is achieved faster than in normotensive conditions: the isolated kidney reacts similarly to the hypertensive patient. The renal response to hypertension as well as to blood dilution is autonomous and does not require extrarenal hormonal control.The present work has been performed with the help of the Fonds National de la Recherche Scientifique (Belgium).