摘要:

AbstractSix metal binding agents were screenedin vivofor their ability to mobilise nickel from the brain, heart, kidney and liver of nickel poisoned rats. Out of these, 1,2 cyclohexylene dinitrilotetraacetic acid (CDTA) was most effective in removing the metal from the heart (78 %) followed by brain (76 %), kidney (65 %) and liver (57 %) whereas diethyl‐dithiocarbamate (DDC) was more effective in the order of heart (85 %), liver (51 %), kidney (44 %) and brain (32 %). Underin vitroconditions, CDTA, diethylene triaminepenta‐acetic acid (DTPA) and nitrilotriacetic acid (NTA) were found to be more effective in dialysing out nickel from the subcellular fractions of liver and kidney and the blood corpuscles of rats prctreated with nickel sulphate. In general, no correlation between the chemical structure or molecular weight of the chelators and their ability to remove nickel from the biological system was obser

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03136.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe uptake process of14C‐neostigmine in striated muscles was studied using the isolated rat diaphragm. Hemidiaphragms were incubated with 3 × 10‐7M14C‐neostigmine at 37° in Krebs‐Ringer solution containing 11 mM glucose and aerated with oxygenxarbon dioxide (95:5 v/v %). The uptake, which is expressed as the muscle‐to‐medium concentration ratio, was 1.41, after 3 hours, after which the rate of uptake diminished and became equal to that of inulin. The uptake which showed partial saturation, was decreased by some tertiary and quarternary amines, metabolic inhibitors, potassium and in an atmosphere of nitrogen. Neostigmine accumulated in all parts of the muscle without preference for the end plate zone. The half‐time for the efflux was about 30 min. The phrenic nerve‐diaphragm preparation became desensitized to the effect of 3 × 10‐7M neostigmine after 2–3 hours. It is suggested that the uptake of neostigmine is mediated via a specialized ca

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03137.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe uptake and retention of14C‐bretylium was studied in rat salivary glands and iridesin vivoat different time intervals after sympathetic denervation or decentralization. The uptake of bretylium was increased on the denervated side during a time period which precedes the degeneration release of sympathetic transmitter, but was later on reduced. On the other hand, the retention of bretylium on the denervated side was already markedly reduced during the time period preceding the onset of the degeneration transmitter release. In experiments with chronically denervated salivary glands, or glands atrophied by means of excretory duct ligation, a pronounced extraneuronal accumulation was observed. The extraneuronal accumulation of bretylium may partly mask the changes in disposition of the drug induced by the sympathetic denervation. The results are in accordance with the hypothesis that bretylium must be associated with special sites at the adrenergic nerve terminals in order to exert its degeneration delaying effec

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03138.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe purpose of this study was to determine whether lithium also inhibits hormone‐stimulated adenylate cyclasein vivo. The effect of long‐term lithium treatment on unstimulated and glucagon‐stimulated cyclic AMP excretion was studied in the rat and in man. The influence of lithium on plasma glucagon degradation was also investigated. It was found that in the rat lithium doubled unstimulated and glucagon‐stimulated urinary cyclic AMP excretion. In lithium treated rats plasma glucagon concentrations thirty minutes after intraperitoneal injection were twice that of the control rats. In man, lithium affected neither cyclic AMP excretion nor glucagon degradation. These results offer no support for the hypothesis thatin vivolithium in general inhibits hormone‐stimulated adenylate cyclase. However, in the intact organism lithium may have additional pharmacological actions, and complex regulatory mechanisms which may modify the cyclic AMP metabolism. Therefore it may be premature to conclude that lithiumper sedoes not have an inhibitory action on glucagon‐sensitive adenylate cyc

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03139.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe properties of various components of a drug‐oxidizing mono‐oxygenase system in the liver of trout (Salmo trutta lacustris) were studied. The concentration of the cytochrome P‐450 was about 7 nmol/g liver wet weight when measured in the 12,000 × g supernatant and 0.2 nmol/mg protein when measured in the “microsomal” fraction. The activity of NADPH‐cytochrome c reductase was about 2000 nmol cyt. c reduced/g liver/min. measured in the homogenate and 20 nmol/mg protein/min. when measured in the “microsomal” fraction. The distribution of the cytochrome P‐450 into different centrifugal fractions indicates that it is localized in the endoplasmic reticulum. The cytochrome P‐450 present in the fish liver microsomal fraction was capable of interacting with different substances resulting in type II (aniline, n‐octylamine, cyanide) and a reversed type I (n‐butanol) spectra. Substances producing type I spectra in the rat liver microsomes, did not give any spectra (hexobarbital, SKF 525A) or gave unclassified spectral changes with the fish liver cytochrome P‐450 (bromobenzene, DDT, piperonyl butoxide). Spectral dissociation constants were calculated for aniline and n‐octylamine. Further experiments indicated that the mono‐oxygenase system in the trout liver microsomes can metabolize aminopyr

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03140.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe effect of methotrexate (20 mg/kg intramuscularly) on the absorption of phenobarbitone, sulphafurazole, mecamylamine, quinidine and isoniazid from the rat small intestine was studiedin situandin vitro. The disappearance of all drugs studied from the intestinal fluidin situwas retarded on the third day after methotrexate administration. The fluid transfer and the amount of drugs passed through the intestinal wallin vitrowere also decreased. The absorption of phenobarbitone was reversible within six days, whereas the absorption of quinidine was still retarded on the sixth day after methotrexate administration. Methotrexate did not modify the amount of quinidine excreted into the intestinal lumen after intravenous administration. The levels of other drugs except isoniazid in the blood at the end of the experiment showed changes corresponding to their disappearance from the intestinal lumen.In situthe drug levels in the intestinal wall were much lower thanin vitro. Their levels in the intestinal wall reflected drug absorptionin vitrobut notin situ. The methotrexate‐induced reversible decrease in absorption seems to be attributable at least partly to diminished water flux through the intestinal wall, although other mechanisms may also exis

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03141.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe effect of chlorhexidine (Chx) and cetrimonium bromide (Ctab) on the haemolysis of erythrocytes has been studied. A concentration dependent release of haemoglobin was observed in isotonic media, with total haemolysis at 80 nmol Chx per 107cells and 20 nmol Ctab per 107cells. The rate of haemolysis induced by Chx shows a biphasic pattern in contrast to the uniphasic pattern of Ctab. In concentrations below 10 nmol per 107cells, Chx produces more haemolysis than Ctab whereas the opposite effect is observed at higher concentrations. Chx and Ctab stabilize the erythrocyte membrane against hypotonic shock. The concentrations of Chx and Ctab giving maximal stabilization are 0.25 nmol per 107cells and 2 nmol per 107cells respectively. The normal biconcave disc form of the erythrocytes is converted to cup forms and in‐vaginated spheres by Chx and Ctab. The binding of Chx to erythrocytes in isotonic media increases linearly with the total concentration up to about 25 nmol Chx per 107cells where the curve has a point of inflection. With more than 25 nmol Chx per 107cells the amount of Chx bound again increases linearly up to 120 nmol per 107cells. The slope of the curve above the point of inflection is approximately 4 times that of the curve below this point. No level of saturation of the binding is observed at the concentrations of Chx used in this study. The mode of action of Chx on erythrocyte membranes is discussed in the light of the present result

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03142.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractIn order to study how acetylation affects the activity of sympathomimetic amines the effects of tyramine, amphetamine, ephedrine, phenylephrine, orciprenaline and their O‐ and N‐acetyl derivatives on acute toxicity, locomotor activity and barbiturate anaesthesia time were studied. N‐acetylated derivatives were always significantly less toxic whereas O‐acetylated derivatives except O‐diacetylphenylephrine were more toxic than the parent compounds. Amphetamine>ephedrine>tyramine increased locomotor activity of mice. O‐acetylephedrine had a similar though weaker effect in this respect than ephedrine. O‐acetyltyramine and N‐acetylated derivatives of tyramine, amphetamine and ephedrine reduced the locomotor activity of mice. Phenylephrine and its O‐ and N‐acetyl derivatives reduced the locomotor activity of mice to about the same degree. Amphetamine>ephedrine>O‐acetylephedrine>tyramine reduced the duration of barbiturate anaesthesia, whereas this was prolonged by adrenaline, N‐acetyltyramine, N‐acetylamphetamine and N‐acetylephedrine. The results show that N‐acetylation decreased or even reversed the action of the parent compound. O‐acetylation increased toxicity but reduced the other effects of the drugs studied. It is probable that the effects of O‐acetyl derivatives are at

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03143.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractMale Sprague‐Dawley rats were given a single intraperitoneal dose of a thioxanthene neuroleptic, thiothixene. The effect on the spontaneous motor activity and the level of homovanillic acid in the striatum and the olfactory tubercle were studied at various times after the injection of the drug. The concentration of thiothixene in the blood and brain was also followed. The rats showed a significant decrease in motor activity from 15 min. to 12 hours after the injection. The HVA‐levels in the striatum and olfactory tubercle were significantly elevated from 0.5 to 18 hours, the effect on the striatum being relatively more pronounced. No clear relation between drug levels and changes in motor activity of HVA‐levels was

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03144.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe binding of digitoxin to purified human serum albumin was studied under equilibrium conditions. The binding affinity was uninfluenced by the strongly bound free fatty acids of the albumin. All bile acids studied were found to inhibit the binding of digitoxin to albumin. Cholic acids and desoxycholic acid induced a competitive inhibition of the digitoxin‐albumin interaction without any physical signs of protein unfolding. Surface active organic anions, known to produce conformational changes of albumin, were found to be powerful inhibitors of the digitoxin‐albumin interact

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03145.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY