三种类型螯合剂对汞在体内分布和排泄影响

小白鼠im~(203)HgCl_2 185kBq/鼠后,立即ip螯合剂,发现在多羧多胺、磷酸、巯基三种类型15个螯合剂中,有7个具有提高排汞的作用,其中以吡哆醇衍生物、半胱氨酸对甲苯磺酸盐及二巯基丁二酸钠(DMS-Na)促排效果较好,分别提高24h尿汞排泄4.6、11.5及22倍,脏器中~(203)Hg含量以DMS-Na组为最低,半胱氨酸对甲苯磺酸盐组次之,但与DMS—Na组相比,相差不显著。     

Pharmacokinetics of stobadin and of the sum of its metabolites in rats during repeated administration

Stobadin dihydrochloride was administered p.o. to rats at a dose of 1 mg kg-1 once daily for 25 consecutive days. The peak and trough concentrations of the sum of stobadin metabolites, determined from Days 6-16 of treatment, demonstrated a steady-state. The mean daily excretion of 3H-radioactivity during this period was 43 per cent and 52 per cent of the administered dose into urine and faeces, respectively. The terminal half-life of stobadin in plasma following a 25-day chronic treatment was 78.3 min, which was shorter than the value of 95.3 min, determined in a single dose experiment. The data indicate that no accumulation of stobadin and of its labelled metabolites occurs in the course of repeated administration of 3H-stobadin.     

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.     

The control of sodium excretion following saline infusion in dogs

Summary The increase in fractional excretion of sodium following intravenous infusion of saline has been investigated in dogs fed with sodium-rich or poor diets after transplantation to the neck of these animals of kidneys removed from dogs submitted previously to either diet. The response of in situ and of transplanted organs has been compared in the four possible combinations of perfusors and kidney donors. No significant differences were observed between the four series, for the same net saline load, in arterial and venous pressures, extravascular and intravascular expansion, or blood dilution. The response in each series was independent of extracellular expansion and was best related to the degree of blood dilution. However, the magnitude of the response to the same net saline load depended on a resetting of the sensitivity of the kidney itself to the blood changes, this resetting depending on the previous dietary sodium balance. This sensitivity was related also to the presence in the blood of a potentiating material which might be, at least partly, of renal origin, and which might represent an intrarenal mediator of the natriuretic response.This work has been performed with the help of the Fonds National de la Recherche Scientifique of Belgium.     

Parathormone as a mediator of inorganic phosphate diuresis during saline infusion in the rat

Summary Normal rats were infused with isotonic saline at 0.50 ml/min for 2 hours in order to expand their extracellular fluid volume. Under these conditions fractional excretion of inorganic phosphate was found to be as high as 38.8±3.0% of filtered phosphate, while fractional sodium excretion was 12.9±0.7% of filtered sodium. The combined addition of calcium and magnesium to the infusion solution decreased inorganic phosphate excretion significantly (P<0.001) to 11.2±3.6% (presumably by inhibiting parathyroid gland activity), while sodium excretion was unchanged (13.5±1.1%). Parathyroidectomized rats were infused with isotonic saline at 0.50 ml/min to achieve a similar extent of extracellular fluid volume expansion as in the normal rats. In these animals inorganic phosphate excretion was as low as 0.9±0.9% of filtered phosphate, while sodium excretion was 11.8±2.2% of filtered sodium. Administration of parathormone to volume expanded parathyroidectomized rats resulted in marked increases or inorganic phosphate excretion to 41.5±3.1% of filtered phosphate (P<0.001), while sodium excretion remained unaltered (12.0±2.8% of filtered sodium), thus resembling very closely the results in normal volume expanded rats.From these results it is concluded, that saline induced phosphaturia in normal rats is mediated primarily by parathormone. Furthermore, sodium excretion during volume expansion of extracellular fluid appears to be independent of inorganic phosphate excretion and independent of changes in parathyroid activity.This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft.     

Exposition au Styrène. I. Etude expérimentale de l'absorption et de l'excrétion pulmonaires sur des sujets humains

Summary Volunteers were exposed in a controlled environment chamber at different concentrations of styrene in order to determine the quantity and percentage of the solvent absorbed and eliminated by the lungs. As a result of these experiments, it was found that the absorption rate of styrene is constant during the exposure at a level representing 88,7 ± 3,4 % of the inspired concentration. The proportion of solvent eliminated by the lungs was only of 2,62 ± 0,85 % of the absorbed dose, while the rate of decay of alveolar concentration curves with respect to time is independent of the steady inspired concentration during exposure. Accordingly, breath decay curves can be used as a method to monitor time weighted average exposure.

     

The adaptation of renal urea excretion after unilateral nephrectomy and after overloading with urea

Summary Urea and inulin clearances were measured in unanesthetized rats 5 and 50 h, and 2–3 weeks after unilateral nephrectomy. At identical i-v infusion rates, urine flow in the uninephrectomized animals was similar to that of sham-operated controls. In the low range of urine flow rates, fractional urea excretion was higher in recently uninephrectomized animals than in controls. The increase appeared to be the consequence of the increased fractional excretion of water. At higher rates of urine flow, and after large loads of urea, the single kidney excreted urea in a manner similar to that of control kidneys. Urea clearances were, in 148/150 clearance determinations, lower than the simultaneously measured inulin clearances. A large increase of GFR was observed in rats chronically loaded and acutely infused with urea.Supported by Fonds National Suisse de la Recherche Scientifique, Grant No. 3440.70.     

Urinary excretion of perphenazine and its sulfoxide during administration in oral and long-acting injectable form

Urinary excretion of the unchanged drug and perphenazine-sulfoxide was measured in a group of patients receiving at first oral perphenazine (24 mg dd) and after some weeks perphenazine-enanthate, a long-acting injectable preparation (100 mg per 14 days). A significant decrease in the absolute quantities of unchanged perphenazine and of the sulfoxide was observed. There was no constant ratio between the quantities excreted. A relative increase in the excretion, expressed in percentages of the administrated dose, was demonstrated.The author wishes to express his gratitude to W. De Waard, psychiatrist, who supervised the clinical trial in this Hospital, for his cooperation and Miss M. Potman, Mr. R. Van Elk and Mr. A. Van de Weerthof for their technical assistance.     

Demethylation and cleavage of glycosidic bonds of 4‴-methyldigoxin in man

Summary In man the oral or intravenous administration of 4-methyldigoxin yields metabolites in urine which are soluble either in chloroform or in water. The chromatographic analysis reveals demethylation as the main metabolic reaction in man. In addition to methyldigoxin and digoxin small amounts of digoxigenin-bisdigitoxoside and digoxigenin-mono-digitoxoside can be detected. The water soluble metabolites represent 7% of the radioactivity excreted in 7 days reaching a maximum within the first 8 h.