摘要:

AbstractThe effect of 10 mM fluoride on glycerol productionin vitrofrom rat epididymal adipocytes was investigated. Fluoride had no effect on the basal glycerol production, irrespective of the presence or absence of Ca++and Mg++ions. When stimulating the glycerol production with 10 mM theophylline, fluoride reduced the stimulation in the absence of either Ca++or Mg++or both. In the presence of both ions, fluoride had no effect on the theophylline stimulation. Fluoride also reduced the stimulative effect of adrenaline on glycerol production, but not that of glucagon. Increased adrenaline concentration could not overcome the inhibitory effect of fluoride.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02130.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe release from the depot, hydrolysis and distribution in the organism as well as the metabolism and elimination of intramuscularly injected Clopenthixol decanoate in Viscoleo® have been studied in dogs and rats with radioactive as well as non‐labelled drug after single as well as repeated administration. The studies clearly demonstrate the depot effect of Clopenthixol decanoate given intramuscularly in oil compared to orally administered clopenthixol. The amounts of drug remaining at the site of injection in dogs suggest monoexponential release of drug from the depot and a half‐life of 4‐5 days. Rapid hydrolysis to Clopenthixol in the organism was indicated byin vitroexperiments andin vivofindings. Clopenthixol was found to be the main compound in the organism after single as well as repeated doses. The Clopenthixol formed by hydrolysis appeared to be metabolized in the same way as clopenthixol given orally i. e. by dealkylation of the side chain and by S‐oxide and N‐oxide formation. The elimination pattern with predominant fecal excretion also appeared to be the same after Clopenthixol and its esterified derivative apart from the reflection in the latter case of the slow release from depot. A rapid exchange in the organism between tritium from the drugs and hydrogen from the body water was demonstrated. This has to be considered in studies with tritium labelled drugs, where estimation of total radioactivity gives the sum of tritium in drug, metabolites

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02131.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractA low blood selenium level has previously been observed in healthy inhabitants of Finland (Westermarcket al.1977). In this study even lower blood selenium values were observed in patients with acrodermatitis entero‐pathica, dystrophia musculorum progressiva (Duchenne), infantile and juvenile type of neuronal ceroid lipofuscinosis (NCL), severe mental retardation caused by various factors, and myocardial infarction. The selenium content of the brain, heart, kidney and liver in patients of different ages was also determined. The highest selenium level was found in the kidney. The mean liver selenium concentrations in stillborn, premature and full‐term neonates were 1.11 ± 0.23 (8), 1.21 ± 0.17 (12) and 0.93 ± 0.16 γg/g dry weight (12) respectively (the number of subjects in parentheses). The selenium values are considerably higher than those in infants of from one to nine months of age and adults, whose liver selenium values were 0.58 ± 0.21 (8) and 0.67 ± 0.08 γg/g dry weight (8) respectively. The vitamin E levels of serum in patients with NCL, as well as in subjects with severe mental retardation (controls), were low compared with values in healthy normal subjects. Sodium selenite supplementation in patients with NCL produced at least a transitory improvement without causing any toxic effects during one year of admi

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02132.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractRats were pretreated either by the injection of 3‐methylcholanthrene (MC) 40 mg/kg intraperitoneally for 3 days or by giving phenobarbitone (PB) 0.5 g/1 in the drinking water for 7 days. Benzo(a)pyrene (BP) and its metabolites were measured by thin‐layer chromatography (TLC) and radiometry in samples of perfusion medium up to two hours. In perfusion medium the half‐life of BP was about 15 min. in the perfusions of lungs from MC‐pretreated rats and 60‐90 min. in the perfusions of lungs from PB‐pretreated and control rats. The appearance of water‐soluble metabolites was most marked in the perfusions of lungs from MC‐pretreated rats being at fifteen minutes 2.5‐fold and at two hours 2‐fold in comparison to the controls. In the perfusions of lungs from PB‐pretreated rats the accumulation was retarded perhaps indicating an inhibition of lung enzymes by PB. Water‐soluble metabolites included glucuronic and sulphuric acid conjugates as well as those conjugates resistant to acid hydrolysis. Phenols were the most pronounced organic‐soluble metabolites at the beginning of perfusion of lungs from MC‐pretreated rats. At fifteen minutes the amount of phenols in the perfusions of lungs from PB‐pretreated rats was 1/6 and in controls 1/3 of that in the perfusions of lungs from MC‐pretreated rats. Towards the end of perfusion phenols decreased in the perfusions of lungs from MC‐pretreated rats. In other perfusions all metabolite fractions increased slowly during the perfusion. Covalently bound radioactivity and BP‐hydroxylase in lung homogenates were studied after perfusions. The covalent binding of radioactivity in the lungs from MC‐pretreated rats was 3.5 times higher than in control lungs and the lungs from PB‐pretreated rats. There was a correlation between covalent binding and the activity of BP‐hydroxylase in lung homogenates. Exposure of rats to cigarette smoke resulted in effects on the BP metab

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02133.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe actions of neurotensin and (Gln4)‐neurotensin have been investigated on a number of isolated tissues. They were ineffective in contracting the guinea pig vas deferens, the rabbit aortic strip or the frog rectus abdominis muscle in concentrations up to 0.24 γM. Neurotensin and (Gln4)‐neurotensin relaxed the rat duodenum at fairly high concentrations (24 nM). The guinea pig ileum contracted in response to increasing doses, although the maximum response were only one half that caused by histamine. Tachyphylaxis was observed at dose intervals of less than 12 minutes, but this tachyphylaxis did not inhibit responses to acetylcholine, histamine, 5‐HT or to DMPP, suggesting that the neurotensins may act at specific receptor sites. They contracted the rat fundus strip at concentrations of 0.24 nM and higher. The neurotensins and 5‐HT were approximately equipotent on this tissue, although the maximum respones was about 80 % of that to 5‐HT. The contractions of the rat fundus strip could not be blocked by atropine, hexamethonium, methysergide, morphine or by 7‐OH‐THC. These data indicate that neurotensin and (Gln4)‐neurotensin are equipotent as far as smooth muscle stimulating activity is concerned. Of those organs tested, the rat fundus strip seems to be the most suitable one for studies concerning structure‐acti

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02134.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe blood cell/plasma concentration ratio of quinidine, as influenced by the plasma protein binding, was studied in normal and anuric rats by applying incubation and equilibrium dialysis techniques on blood and plasma, respectively, from normal and anuric rats. The plasma protein binding of quinidine in anuria was increased at concentrations of unbound drug of less than 1.75 × 10‐4M and decreased above this concentration. At an assumed “therapeutic” quinidine concentration (1 × 10‐5M), the mean concentration ratio (total quinidine in blood cells)/(total quinidine in plasma) was 1.84 in normals and 0.46 in anuria, and the mean ratio (total quinidine in blood cells)/(unbound in plasma) was 4.45 and 1.81, respectively. As the latter ratios were concentration dependent and greater than could be accounted for by pH‐dependent distribution, quinidine is presumably bound in/on the blood cells. Reduced distribution ratio in anuria, even when related to unbound quinidine in plasma, also indicates changed binding in blood cells, a finding confirmed by applying the data to modified Scatchard plot. This may have implication for the use of blood cell/plasma concentration ratio as screening procedure for the altered plasma binding of quinidine

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02135.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

AbstractThe pharmacokinetics of quinidine were investigated in normal and anuric rats after intravenous injection (25 mg per kg b. wt.). In normal rats only 2.6 percent of the injected dose was excreted as unchanged quinidine in the urine. Quinidine concentrations were determined in the blood and in different tissues after injection, and the serum protein binding was measured. Results were applied to a one compartment model. In normal rats a total body clearance of 18.5 ml/min. and a renal clearance of 0.5 ml/min. was found. The residual non‐renal clearance (18.0 ml/min.), presumably taking place in the liver, exceeds the estimated liver blood flow (16.8 ml/min.), indicating efficient extraction of quinidine from plasma and blood cells (non‐restrictive elimination). The apparent volume of distribution was greatly reduced, biological half‐life slightly longer and the body clearance greatly reduced in anuric as compared to normal rats. The fraction of unbound quinidine in serum was 30.6 ± 0.6 (n=23) and 16.7 ± 0.5) (n=23) percent in normal and anuric rats. The reduction in the apparent volume of distribution is mainly explained by increased serum binding. The decline of body clearance of quinidine is most likely caused by a decreased liver blood flow in this complex state of renal insuff

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02136.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

Abstract1. Incubation of liver microsomes from phenobarbital‐treated rats with N‐hydroxyamphetamine or norbenzphetamine in the presence of NADPH and molecular oxygen gave rise to the formation of a cytochrome P‐450‐product complex characterized by maximal light absorption at 456 nm. Complex formation was more rapid and extensive with N‐hydroxyamphetamine than with norbenzphetamine as substrate.2. When incubation was performed with hepatocytes isolated from phenobarbital‐treated rats, the formation of the cytochrome P‐450‐product complex was less rapid as well as less extensive. In fact, with some cell preparations incubation with norbenzphetamine failed to produce any spectrophoto metrically observable cytochrome P‐450‐product complex.3. Incubation of the hepatocytes with norbenzphetamine caused a decrease in the cellular level of reduced glutathione (GSH) suggesting consumption of GSH during the metabolism of the drug. Moreover, GSH and certain other sulfhydryl compounds inhibited norbenzphetamine‐induced cytochrome P‐450‐product complex formation in the liver microsomal fraction. The extent of inhibition by GSH was moderately enhanced by the addition to the microsomes of a purified preparation of glutathione‐S‐epoxide transferase.4. When higher concentrations of norbenzphetamine (>1 mM), or certain other lipophilic amines, were added to suspensions of hepatocytes, there was a rapid lysis of the cells which was preceeded by a dramatic decrease in the cellular ATP level. This effect could be correlated to uncoupling of phosphorylation from respiration in experiments on isolated rat liver mitochondria.5. It is suggested that further metabolism via a GSH‐linked pathway may act by decreasing the concentration of cytochrome P‐450‐binding norbenzphetamine metabolite(s) in the hepatocyte, thus inhibiting cytochrome P‐450‐product

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02137.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1977.tb02138.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY