摘要:

Ethanol was given as short‐term treatment to intact animals in the following ways: Orally in mixture with sucrose as drinking fluidad libitumfor one or 18‐21 hrs, or intraperitoneally (i.p.) as a single dose (2.5 or 3.3 g/kg rat). Ethanol was also added to perfusates (final concentration 0.2 %) of isolated livers. Short‐term ethanol treatment (in vivo) was also given to animals which had been pretreated with ethanol for 3‐4 weeks.I.p. injection of ethanol caused a significant rise in tryptophan oxygenase (TO)‐activity (337 %) and plasma corticosterone (approximately 400 %), while consumption of ethanol only slightly increased the enzyme activity without any significant effects on steroid hormone concentration. The administration of cycloheximide (1.5 mg/kg) abolished the increase in TO‐activity normally found after i.p. injection of ethanol. Ethanol did not affect the basal TO‐activity in the perfused liver, but slightly increased the effect of dexamethasone induction. TO degradation measured after administration of cycloheximide (20 μg/ml) was unchanged by ethanol in the perfused liver. An i.p. injection of ethanol increased the TO‐activity (268 %) in ethanol‐pretreated rats, but to a smaller extent than in normal animals. The TO‐activity measured after consumption in ethanol‐pretreated rats was significantly reduced. It was concluded that the acute stimulatory effect of ethanol on TO‐activity was due to the rise in plasma corticosterone which induced enzyme synthesis. Long‐term consumption of ethanol was accompanied by reduced basal TO synthesis as well as by reduced enzyme induction aft

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb00755.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

The half‐life of propylthiouracil was determined in 7 normal subjects after intravenous injection of 400 mg of the drug. An average value of 77 ± 17 minutes (mean ± S. D.) was found. As the concentration of the drug in the blood declined by a rapid phase followed by a more slow phase a two‐compartment model was used for further calculations, and the rate constants between the 2 compartments and the overall elimination constant have been calculated. The same dose of propylthiouracil was later administeredper osto the same 7 persons and the plasma concentration was followed to non‐measurable values. An average maximum concentration of 9.1 ± 2.5 μg/ml was obtained after a period of 57 ± 22 minutes. The area under the “peroral” curve has been calculated in per cent of the area under the “intravenous” curve. An average value of 77 ± 13 % was found expressing the bioavailability of the drug after

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb00756.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

For 2 months, two groups of rats were given food containing 0 and 40 mmol lithium/kg dry weight, respectively. Most of the lithium‐treated rats gained weight, although at a lower rate than the control rats. They showed no significant changes in intra‐arterial blood pressure (determined in sodium amytal anaesthesia), plasma renin substrate, or plasma renin. A few lithium‐treated rats lost weight and developed severe lithium intoxication. Their blood pressure was also unchanged, but they showed a fall to zero in plasma renin substrate concentration. In another experiment lasting 9‐18 days, two groups of rats were given food containing 0 and 70 mmol lithium/kg dry weight, respectively. The lithium‐treated rats developed severe lithium intoxication. Their intra‐arterial blood pressure was unchanged; plasma renin substrate showed a pronounced decrease and plasma renin a marked increase. The results do not support previous observations of a lithium‐induced blood pressure increase. They indicate that animals with severe lithium intoxication resemble adrenalectomized animals given an insufficient sup

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb00757.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

The acute cardiotoxic effects of adriamycin and daunorubicin have been studied in isolated, perfused rat hearts. Both drugs caused a dose‐dependent decrease in rate and contractile force as well as changes in the ECG indicating a general retardation of impulse propagation. The presence of 0.47 mg/ml of herring sperm DNA in the perfusate greatly reduced the cardiotoxic effect of both drugs. The reduced toxicity is probably due to the binding of the drugs to DN

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb00758.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

Post mortem serum concentrations of cardiac glycosides have been measured in 13 patients who had suddenly died from suspected overdosage of cardiac glycosides. With digoxin, the highest level observed was 71 ng/ml after an intramuscular injection to an infant, whilst levels of 7.2 to 24 ng/ml were found after oral administration to adults. These levels are much higher than the mean therapeutic levels, which were 1.34 ng/ml for optimally digitalised patients and 3.11 ng/ml for those showing evidence of toxicity, although some overlap did occur. Other cardiac glycosides (digitoxin, lanatoside C and deslanoside) showed a similar relationship between concentrations found during therapy and after overdosage.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb00759.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

Rats were given lithium with the food in a dose which maintained the serum lithium concentration at about 1.0 mM. Morphine, given subcutaneously in a dose of 8 mg/kg body weight, was administered both acutely and chronically. Lithium increased the analgesic effect of morphine but did not affect tolerance development. Following chronic morphine administration, lithium increased the hyperthermic action of morphine and the morphine‐induced motor hyperactivity. The interaction of lithium with morphine may take place through brain amines and brain cyclic AM

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb00760.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

Rats were given food containing lithium in amounts leading to serum lithium concentrations of 0.6‐1.1 mM, and the urinary excretion of cyclic AMP after subcutaneous injection of glucagon was determined. The unstimulated cyclic AMP excretion was the same in the lithium‐treated and in the control rats, but after glucagon administration the lithium‐treated rats excreted significantly higher amounts of cyclic AMP than the control rats. This occurred whether lithium had been given during two days or six weeks before the glucagon injection. At all dose levels of glucagon, within the range of 50‐1000 μg/kg b. wt., the response of the lithium‐treated rats was about 70% higher than in the control rats. The increased cyclic AMP excretion was not due to the lithium‐induced polyuria since the difference between the lithium‐treated rats and control rats was also present when polyuric lithium rats were compared with polyuric control rats. The higher excretion of cyclic AMP could not be accounted for by an increased activity of the adenyl cyclase or a decreased degradation rate of cyclic AMP measured in liver homogenates. A somewhat lowered binding capacity of the protein kinases for cyclic AMP was found in the lithium‐treated rats; this might cause or contribute to the increased urinary cycl

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb00761.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

Median threshold concentrations for the sensory irritant material dibenz(b.f)‐1:4‐oxazepine (CR) to produce blepharospasm were found to be 7.9 × 10‐5M for the rabbit, 3.5 × 10‐5M for the guinea pig and 8.6 × 10‐7M for man. The threshold concentration to produce sensation on the human eye was 4.9 × 10‐7M. Extrapolation of log‐probit plots for sensation on the human eye suggests that 3.3 × 10‐6M would be incapacitating. The median threshold concentration of CR required to produce sensation on the human tongue was 2.1 × 10‐6M; a concentration 4.3 times that required to produce sensation on the eye. These values have been compared with those previously estimated for the sensory irritant material o‐chlorobenzylidene malononitrile (CS). Species variation in responses and the problems of predicting comparative irritancy in man from ani

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb00762.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

The selenium carrier proteins in mouse plasma were studied using75Se‐selenite and a crossed immunoelectrophoresis‐autoradiography.The selenite was not bound to plasma proteinsin vitrounless erythrocytes were present. Intravenously administered selenite was attached to the same proteins as the selenite‐Se metabolized by the erythrocytesin

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb00763.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb00764.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY