ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03622.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractFour new synthetic indoles have been found to suppress the synthesis of collagen both in incubated granuloma–slices and in detached embryonic–chick tendon cells as well as to decrease the secretion of collagen to the extracellular space, the latter of which was also inhibited by a membrane–active detergent. The effects of serotonin and indomethacin were studied as a background and data are presented on the association of serotonin to plasma membrane fractions. The synthesis of collagenin vitrois suggested as a useful test in the preliminary screening of potential antirheumatic

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03150.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractIsolated rat liver cells were used in the study of p–nitroanisole and p–nitrophenol metabolism.p–Nitroanisole was o–dealkylated to formp–nitrophenol which was subsequently conjugated to form predominantly sulphate esters and β–glucuronides.1. At low concentrations ofp–nitrophenol, sulphate conjugation was predominant but with increasing substrate concentration the glucuronidation activity was increased. At 250 μMp–nitrophenol the major conjugate formed was glucuronide while sulphate conjugation was inhibited.2. Withp–nitroanisole in low concentration, resulting in low oxidation rate, all thep–nitrophenol formed was further conjugated to sulphate esters. With higher phenol production, glucuronide conjugates were also formed.3. Phenobarbital treatment of the rats increased the rate of p–nitroanisole oxidation by more than four times but had very little effect on the conjugation reactions. In these cells the major conjugate formed was glucuronide.4. The rate of glucuronidation in the isolated liver cells was higher than in microsomes and responded differently to various inhibitors. Alprenolol, a substrate of the hepatic mono–oxygenase system, had no inhibitory effect on glucuronidation in microsomes in the absence of NADPH. However, low concentrations of alprenolol showed similar inhibitory effects in microsomes in the presence of NADPH as in isolated liver cells.5. Nitrophenol glucuronide was strongly inhibitory to the glucuronidation in microsomes while almost no inhibition was observed in the isolated liver cells, probably due to poor penetration of the glucuronide through the cell membrane.6. Rotenone, menadione and ethanol had little effect in microsomes but were potent inhibitors of glucuronidation in the isolated liver cells, most probably by interfering with the synthesis of UDPGlcA.The effect of ethanol was maximal at as low a concentration as 10 mM and was shown to be due to alcohol dehydrogenase–dependent ethanol oxidation. The inhibition was presumably caused by the the increased cytoplasmic NADH/NAD4ratio resulting fro

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03151.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe biliary clearances of3H–mannitol (5 and 50 μmol/kg) and3H–ibuterol (diisobutyrate ester of terbutaline) (0.5 and 5 μmol/kg) after intraarterial administration have been studied using unanaesthetized rats with uninterrupted enterohepatic circulation. The mean bile flow was 0.08 ml/min./kg. The biliary clearance of mannitol ranged from 0.06–0.17 ml/min./kg. The biliary clearance of ibuterol and its metabolites (total radioactivity) ranged from 2.05 to 4.81 ml/min./kg and that of the formed terbutaline from 0.53 to 2.05 ml/min./kg indicating a concentrative transfer from the plasma to the bile. The cumulative biliary excretion during the 3 hour sampling period amounted to 1 % of the administered doses of mannitol and 25 % of the doses of i

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03152.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe absorption from the airways, uptake from the vascular compartment and biotransformation of3H–ibuterol (diisobutyrate ester of terbutaline) and3H–terbutaline have been studied using isolated perfused and ventilated rat lungs. After endotracheal instillation, ibuterol was more rapidly absorbed than terbutaline (P<0.01 at 5 and 10 min. after administration) at doses of 55 and 550 nmol/lung. No difference was noted at 5.5 nmol/lung. When the drugs were added to the perfusion medium the calculated lung uptake for ibuterol was about 30 times that for terbutaline. Ibuterol was shown to be rapidly hydrolyzed to terbutaline. No or minor biotransformation of terbutaline was no

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03153.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractMorphine concentrations in the recirculating plasma of a perfused rat liver preparation declined in a monoexponential manner with a half–life of 5.3 ± 0.4 min. The mean hepatic clearance was calculated to 13.1 ± 1.0 ml–min.–1, and using an average blood flow of 17.3 ml min.–1this corresponds to an extraction ratio of 0.76 ± 0.02. In experiments with steady state concentration of morphine almost identical results were obtained. Measurements of different morphine concentrations in the in– and outflow of plasma of the liver yielded a mean clearance of 13.3 ± 0.7 ml–min.–1and a mean extraction ratio of 0.77 ± 0.03, indicating a constant clearance at different concentrations. The clearance of morphine in the perfused liver experiments was in close agreement with anin vivocalculated hepatic clearance of 75 % of the total body clearance. It is concluded that the blood flow to the liver can be an important factor in determining availability of orally administered morphine, and that the high hepatic extraction of this drug can explain the low effectiveness of this mode

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03154.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractLiver homogenized in phosphate buffer was incubated with different amounts of crimidin for 0, 15, 30 or 45 min. The reactions were stopped by heating. The influence of their supernatants on glutamic acid decarboxylase activity in brain tissue was investigated. When 1 g of liver had been incubated with 1.17 or 1.75 μmol of crimidin for at least 30 min., the supernatant significantly reduced the decarboxylase activity; so did supernatants from 2.33 and 3.5 μmol of crimidin per g and this was already seen after 15 min. of incubation. Brain homogenate did not convert crimidin into a compound which could inhibit the decarboxylase activity within the reaction tim

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03155.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe distribution and elimination of 2–methyl–4–chlorophenoxyacetic acid (MCPA) in male rats were studied. 3 mg of14C–labelled and non–labelled MCPA in 50 % ethanol was injected into the stomach of male rats and urine, faeces and internal organs or tissues were analyzed for radioactivity. During the first 24 hrs 92.26 ± 5.36 % of the radioactivity was excreted in the urine and 6.76 ± 3.56 % in the faeces. Recovery in the urine and faeces after five days was 102.78 ± 1.10 % of the dose administered, indicating that practically all MCPA is eliminated in the urine and faeces. The maximum concentrations of MCPA in the tissues occurred between 2 to 8 hrs after administration. Thereafter the concentrations declined rapidly. The highest concentrations of MCPA were observed in the blood, kidney, lung, heart, suprarenal gland, liver, thyroid gland and bone marrow. The lowest concentrations were those in the brain, adipose tissue, testi

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03156.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractTwenty–seven days exposure of 10 male volunteers to marijuana cigarettes containing a total dose of 16 mg of Δ9–tetrahydrocannabinol resulted in a significant reduction in the effect of the drug on heart rate. The results are consistent with and best explained by the hypothesis of tolerance develop

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03157.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe biochemical and histopathological changes in lungs of guinea pigs were studied 120 days after intratracheal injection of three varieties of asbestos dusts, viz. chrysotile, amosite and anthophyllite. The salient histopathological features observed were the development of dust cell lesions in the lungs of animals exposed to the different varieties of asbestos. Maximum fibrosis and minimal asbestos body formation was observed in animals exposed to chrysotile and anthophyllite, respectively. With amosite and anthophyllite the development of diffuse interstitial fibrosis ensued, accompanied by well developed asbestos body formation in the amosite exposed animals. Biochemical studies revealed significant alterations in various phosphorylated compounds, an accumulation of orthophosphate and depletion of esters and nucleotides being very marked. RNA content increased significantly in the amosite treated group while the nucleic acid content remained unaltered in the chrysotile group.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03158.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY