摘要:

AbstractThe phenolic metabolites of biphenyl in guinea pigs and rabbits were qualitatively and quantitatively analysed as trimethylsilyl (TMS) ethers by combined gas chromatography/mass spectrometry and gas chromatography, respectively. The parent compound was hydroxylated to monohydroxylated biphenyls and minor amounts of dihydroxylated derivatives, and the main route of body clearance appeared to be by the urine in both species. Thus, in the urine of guinea pigs 32.9 % of the dose was detected 96 hrs after dosing, while the major part (29.5 %) was eliminated during the first day as conjugates. The main metabolite was 4‐hydroxybiphenyl (25.5 %). During the first 24 hrs faecal recovery was 20.3 % of the dose, and most of this (14.3 %) consisted of biphenyl itself. Biliary excretion of the metabolites of biphenyl origin amounted to 3.3 % of the dose during the first day, and 4‐hydroxybiphenyl was the major metabolite. In the urine of rabbits 49.1 % of the dose was recovered 96 hrs after dosing, and most of this (25.4 and 15.9 %, respectively) was eliminated during the first two days as conjugates. The major metabolite was 4‐hydroxybiphenyl (35.3 %). On the first day faecal recovery was 1.6 %, of which 1.4 % was detected as biphenyl itself. Less than 1 % of the dose was found in the 7 hrs rabbit bile, and exclusively as 4‐hydroxybiphenyl. The experiments thus show that both qualitative and quantitative differences in the metabolism of biphenyl exist between the guinea pig and the rabbit even though 4‐hydroxybiphenyl was the most prominent metabolite of biphenyl in bot

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02068.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe phenolic metabolites of biphenyl in the crustaceanCirolana borealis LILJEBORG(ISOPODA), the gastropodBuccinum undatumL and the ophiuroidOphiocomina nigraABILDGAARD have been analysed qualitatively and semi‐quantitatively as trimethylsilyl (TMS) ethers by combined gas chromatography/mass spectrometry and gas chromatography, respectively. The findings demonstrate thein vivometabolic capacity of these organisms to convert biphenyl into its hydroxylated derivatives. Thus, 2‐hydroxybiphenyl is the most prominent metabolite detected in all these experiments, which also showed that minor amounts of the 4‐hydroxy and 4,4′‐dihydroxy metabolites are formed. Metabolites of biphenyl origin are found both in the sea water from the aquaria and in the tissue of the respective marine organisms. The experiments, moreover, indicate a slow metabolism of biphenyl inC. borealis, B. undatumandO. nigra, between which no qualitative metabolic differences

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02069.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe objective of this study was to investigate the effects of inositol and vitamin D2on bone uptake of45Ca in rats. The radioactive calcium was administered to young rats by orogastric intubation (2 μci/100 g body weight (b. wt.)) with inositol (20 mg/100 g b. wt.) and/or vitamin D2(500IU/100g b. wt.) to normal rats. Bone uptake of45Ca was measured after 24 hours by standard technique. Inositol alone produced a 48 % increase in calcium uptake. It is concluded that inositol significantly increases bone uptake of radioactive calcium (P>0.005). Simultaneous administration of vitamin D2decreases the effect of inositol considerably, while vitamin D2has no significant effect

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02070.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe new sulphonylurea CS 476 has been shown to be a potent hypoglycaemic agent. In normal fasting dogs, rabbits, rats and mice the maximal hypoglycaemia produced by intravenous administration of CS 476 was comparable on a weight basis to that produced by glibenclamide. Randomized Latin square experiments in dogs showed that 0.03 mg/kg orally of CS 476 and of glibenclamide caused the same maximal decrease of blood glucose and that CS 476 had the shorter duration of action. CS 476 had no hypoglycaemic effect in totally pancreatectomized dogs nor in streptozotocin diabetic dogs and rats. The insulin releasing activity was studied in dogs after intravenous and oral administration of equipotent doses of CS 476, tolbutamide and glibenclamide. It was found that the insulin curves after CS 476 tended to have a plateau‐like maximum like those after glibenclamide although the duration of effect was shorte

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02071.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe new sulphonylurea CS 476 does not potentiate the effect of insulin on plasma glucose levels in diabetic dogs in which an oral glucose load does not cause insulin release. In normal dogs propranolol 0.3 mg/kg intravenously inhibites the insulin release and the hypoglycaemia due to CS 476 suggesting involvement of β‐adrenergic receptors in its action on the pancreas. Pretreatment of dogs with phentolamine leads to an augmentation of the insulin response to CS 4

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02072.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe new sulphonylurea CS 476 was tested for positive inotropic effect on the isolated cat papillary muscle. Unlike tolbutamide CS 476 had no positive inotropic effect. CS 476 had no adverse effect on blood pressure in dogs, cats and rats nor on the electrocardiogram of dogs in doses up to ten times the therapeutic dose. Unlike chlorpropamide CS 476 did not potentiate the effect of exogenous antidiuretic hormone in hydrated dogs. In therapeutic concentrations the drug had no effect on smooth muscle preparations. 1,000–10,000 times therapeutic concentrations had a papaverine‐like effect ‐ similar to therapeutic concentrations of tolbut

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02073.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractSeven subjects received diazepam 0.3 mg/kg intravenously twice with a 2‐week interval between the doses. The subjects ingested a fatty or carbohydrate meal in a cross‐over fashion 4 hours after the injection on both experimental days. Venous blood samples were drawn 2, 3, 4, 5 and 6 hours after the injection of diazepam for measurement of the serum levels of total and free (unbound) diazepam, N‐desmethyldiazepam, and free fatty acids. Serum levels of diazepam decreased progressively with time until the food intake, after which a significant (P<0.01) postprandial increase (average 23 %) occurred with both diets as compared to the preprandial levels at 4 hours (average 240 ng/ml). Serum levels of free fatty acids decreased significantly both after a fatty (P<0.01) and a carbohydrate (P<0.05) meal. Diazepam was extensively (96 to 98 %) bound to proteins and no changes in its protein binding was found. It is concluded that the late impairment of psychomotor skills that occurs with an increase in the diazepam serum level after its intravenous administration is due rather to its re‐mobilization from a storage site than to variations in its protein

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02074.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe effect of five sympathomimetic amines and some of their acetyl derivatives on the blood pressure of the rat was determined on the left carotid artery. After pretreatment with chlorisondamine (1 mg/kg subcutaneously) the blood pressure rise by sympathomimetic amines and their acetyl derivatives was compared with that of adrenaline. If the potency of adrenaline is specified as 100, the potencies of the other drugs are phenylephrine (metaoxedrinum, NFN) 37, tyramine 1.1, O‐acetyltyramine 0.52, amphetamine 0.50, O‐diacetyl‐phenylephrine 0.25, ephedrine 0.23, O‐acetylephedrine 0.02, N‐acetylphenyl‐ephrine 0.01. The effects of N‐acetyltyramine, N‐acetylephedrine and N‐acetyl‐amphetamine are even weaker. Reserpine 5.0 or 0.05 mg/kg intraperitoneally 24 hours before the experiment increased the blood pressure rise by the directly acting sympathomimetic amines and their acetyl derivatives, but decreased the effects of the indirectly acting drugs. After treatment with phenoxybenzamine (2 mg/kg intraperitoneally), adrenaline exhibited the greatest blood pressure decrease and the effects of the other drugs in descending order: orciprenaline, O‐acetyltyramine, phenylephrine, ephedrine, amphetamine, O‐diacetylphenyl‐ephrine and O‐acetylephedrine. Tyramine did not show any blood pressure decrease. The blood pressure decrease by sympathomimetic amines and by their acetyl derivatives was probably due to β‐receptor stimulation because it was prevented by propranolol. The N‐acetyl derivatives recembled their parent drugs with regard to the immediate onset and short duration of their effects. The O‐acetyl derivatives exhibited slower onset and longer duration of effect than their parent drugs. Physostigmine‐pretreatment diminished the rise in blood pressure by O‐acetyltyramine, but the

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02075.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe effects of ouabain 5 × 10‐5M, noradrenaline 10‐7M and nifedipine 100 μg/1 on the contractile force of the isolated rat left atrium were tested and compared at varying concentrations of calcium in the Ringer solution. The effect of ouabain was small, developed slowly and almost independently of the calcium concentration. Noradrenaline, which increases Ca++influx during excitation, caused an increase in the contractile force which was complete within 2 min. The percentage as well as the absolute increase in contractile force was pronounced at lower, but small at higher calcium concentrations. Nifedipine, which reduces Ca++influx during excitation, caused a decrease in contractile force which was complete within 2–4 min. The nifedipine‐induced depression in contractile force decreased with a rise in the calcium concentration. It is assumed that the ouabain‐induced increase in contractile force in the rat, is not mediated by an increase in the magnitude of the inward calcium current, and other modes of action for the inotropic effect of glycosides ar

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02076.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractSingle and/or repeated administrations of bumetanide, bendroflumethiazide and hydralazine to normotensive and spontaneously hypertensive rats resulted in an increase of urinary kallikrein excretion. No correlation was found with sodium output. The role of the increased plasma renin activity is discussed and it is suggested that the activation of the renal kallikrein‐kinin system is related to the increase in renal blood flo

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02077.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY