摘要:

AbstractLithium inhibitsin vitroas well asin vivoseveral hormone‐stimulated adenylate cyclases. The aim of this study was to investigate the mechanism by which lithium inhibits adenylate cyclasein vitro. It was found that lithium inhibited both the norepinephrine‐ and the glucagon‐induced cAMP accumulation in rat fat cells at lithium concentrations above 10 mM. The basal cAMP content was unaffected even at 40 mM of lithium. The inhibitory action was time‐dependent and reversible, indicating an intracellular site of action. Lithium inhibited both norepinephrine‐ and glucagon‐stimulated cAMP accumulation in a mainly non‐competitive way, but the inhibitory effect decreased with increasing hormone concentrations. In accordance, lithium and propranolol had a supraadditive effect on norepinephrine‐induced cAMP accumulation. It is suggested that lithium affects both the hormone‐receptor binding as well as the transfer of the hormonal stimulus by an intracellul

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02401.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe mechanism of action of theophylline was studied by investigating the relationship between relaxant effect and inhibition of cyclic nucleotide phosphodiesterase (PDE) and by studying interactions with adenosine actions. Guinea pig tracheal smooth muscle cyclic AMP PDE had two apparent Kms′: 0.4 and 70 μM for cyclic AMP. Theophylline and papaverine competetively inhibited the low Kmform. Hydrolysis of 2.0 μM cyclic AMP and cyclic GMP was inhibited by several drugs. Some agents (e.g. ZK 62 711, ICI 63, 197, Ro 20‐1724, dipyridamol) were considerably more potent as inhibitors of cyclic AMP than of cyclic GMP hydrolysis, while other agents (M&B 22.948 and dilazep) selectively inhibited cyclic GMP breakdown, and some (theophylline, papaverine, IBMX and SQ 20,006) showed little selectivity. There was a weak but significant correlation between inhibition of cyclic AMP phosphodiesterase and relaxation of tracheal smooth musclein vitro. There was also a correlation between the ratio of IC25 cyclic AMP/IC25 cyclic GMP and the smooth muscle relaxation, indicating that inhibition of cyclic AMP rather than cyclic GMP hydrolysis determined relaxation. However, there was a marked tachyphylaxis to the relaxant effect of the cyclic AMP selective PDE‐inhibitors, while the nonselective methylxanthines did not show tachyphylaxis. The effect of theophylline was antagonized by low concentrations of adenosine, which by itself caused a weak tracheal contraction. The effect of PDE‐inhibitors can be partly explained by decreased cyclic AMP breakdown but other mechanisms, such as antagonism of endogenous adenosine, may contribute to the observed relaxa

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02402.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe effects of a sugar mixture containing 43% glucose and 36% fructose on ethanol metabolism and on ethanol‐induced impairment were studied in intact rats. When ethanol was given orally mixed with the sugars there was a significant reduction in the area of the blood alcohol time curve accompanied by a decrease in the peak ethanol concentration and a slowing in the rate of ethanol absorption. The whole curve followed a lower course and the time for complete removal of ethanol from the body was markedly reduced even though the slope of the elimination phase (β) was not significantly increased. Ethanol‐induced impairment as measured using a tilting plane device was significantly less when ethanol was given mixed with the sugars and paralleled the reduced area and duration of the blood alcohol curve. The magnitude of the effect observed on blood alcohol levels and impairment was dependent on the dose of sugars administered in relation to the alcohol dose. When the sugars were given orally after absorption and distribution of ethanol were complete the slope of the elimination phase (β) was increased by 30%. These findings point to an increased rate of ethanol metabolism in rats in the presence of sugars. The action of the sugars prevails only for the first few hours after administration thereafter the rate of ethanol metabolism returns to n

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02403.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe fate of sesame oil and Viscoleo was studied in dogs after single intramuscular injection into the thigh of14C‐labelled oil (0.5 ml/kg). Parts of Viscoleo was absorbed as liquid oil to the regional lymph nodes occasionally to such an extent that small oil droplets were drained from the iliac lymph nodes into the lymph of the thoracic duct causing pulmonary oil microembolisation. Sesame oil was also absorbed to the regional lymph nodes after single injection but in no case to such an extent that pulmonary oil microembolism occurred. In dogs which received unlabelled sesame oil (0.45 and 1.0 ml/kg) or Viscoleo (0.45 ml/kg) intramuscularly once a week for six months and finally an injection of14C‐labelled oil, pulmonary oil microembolism was seen in all three groups and most markedly after the higher sesame oil dose. The iliac lymph nodes in both sesame oil dose groups were highly enlarged and appeared cystic due to presence of oil. The lungs from the dogs receiving Viscoleo were seat of small mononuclear interstitial cell infiltrations sometimes present in the vicinity of oil microemboli. In the sesame oil groups oil was additionally found extravascularly in the lung interstities together with accumulation of macrophages and leucocytes and focal hemosiderosis in the lungs occurred on the highest dose level. In the sesame oil groups of dogs pulmonary oil microembolism was found microscopically in a higher number than that seen on autoradiograms. The embolisation obtained at one injection may thus not disappear before the next injection. Except for presence of very few oil microemboli and small focal areas with interstitial oil deposits the lungs were normal in dogs examined three months after six month chronic weekly injection of sesame oil. Small oil deposits were still present at the injection site and in the iliac lymph nodes of these dogs, but the lymphoid tissue of the nodes had partly recovered. Pulmonary oil microembolism was also seen microscopically in rabbits after intramuscular injection of sesame oil or Viscoleo three times a week for two weeks, and also in rats after injection of sesame oil three times a week for five weeks. The content of radioactivity in the heart, kidneys, liver and lungs were generally low and the liver had the highest content (up to 1.32% of dose). The content in the lungs was not increased by presence of Viscoleo microemboli whereas sesame oil microembolisation significantly raised the amount of radioactivity in the lungs. The amounts of radioactivity at the injection site of dogs were reduced to half of the injected dose two days after injection of14C‐Viscoleo and five weeks after injection of14C‐sesame oil. In rats receiving an intramuscular injection (0.5 ml) into the thigh of14C‐Viscoleo or14C‐sesame oil the amounts of radioactivity at the injection site disappeared exponentially with time, and half of the dose had disappeared one week after injection of14C‐Viscoleo and 9 weeks after injection of14C‐sesame oil. The acute intravenous toxicity of sesame oil and Viscoleo was estimated in rabbits by determination of the LD50 dose which for sesame oil was 0.74 ml/kg and for Viscoleo 0.84 ml/kg. In the lungs of rabbits receiving 0.5 ml/kg of sesame oil or Viscoleo intravenously, numerous focal haemorrhages were present in the sesame oil group. Four weeks after the injection oil microembolisation was still pronounced in lungs from the sesame oil group while only few emboli were found in lungs from the Viscoleo group two weeks after the injection, In addition sesame oil was found extravascularly in the lung interstities with cellular infiltrate. Thus the pulmonary Viscoleo microemboli disappeared considerably faster than the sesame oil microemboli. In conclusion the present studies have revealed that chronic intramuscular injection of large volumes of two different oily drug vehicles may cause pulmonary oil microembolisation after lymphatic absorption as liquid oil. This occurred in spite of markedly different absorption rates of oil from the injection site. Toxicological implications of the present experiments with intramuscular injections of oil were related to the injection site, the regional lymph nodes and the lungs. Consequently the present finding demonstrate that the regional lymph nodes and the lungs may be the organs of interest in future studies on the relations to the human clinic. If pulmonary oil microembolisation should occur in patients receiving large volumes of oil the pathological sequelae may according to the present findings in animals be wit

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02404.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe effect of methyl mercury and two selenium compounds have been studied in cell cultures. Methyl mercury in concentrations above 1 μM had a pronounced inhibiting effect on the growth of rat Morris hepatoma cells. Glucose and lactate uptake in relation to cell protein was appreciably stimulated by the organic mercury compound. Selenite in low concentrations (0.5 μM) and seleno‐di‐N‐acetyl glycine in thousandfold higher concentrations offered considerable protection against these effects of methyl mercury. The same selenite concentration (0.5 μM), which did not affect cell growth, caused an appreciable protection against methyl mercury (6 μM), even if it was added 3 days after methyl mercury. The methyl mercury inhibited the growth of human embryonic fibroblasts and the DNA‐synthesis in the human lymphocytes. However, no protective effect of selenite were observed in these cell types. These results suggest that selenium compounds exert their protective effects through cell specific processes rather than by a direct chemical reaction between selenite and met

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02405.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe effects of surface‐active alkyltrimethylammonium salts (C10‐C20) on the contractile activity of isolated rat jejunum and on the gastrointestinal motility in anaesthetized rats were studied. The surfactants caused a dose‐dependent depression of spontaneous contractions and of acetyl‐β‐methylcholine and BaCl2induced contractions of isolated rat jejunum. The depressant activity of the surface‐active alkyltrimethylammonium salts on smooth muscle contraction increased with an increase in the length of the alkyl chain to maximum activity at C16. It is suggested that the depressant activity of the surface‐active alkyltrimethylammonium salts on smooth muscle contraction is due to a non‐specific interaction of the surfactants with the cellmembrane of the muscle cells. No effect on gastric and intestinal motilityin vivowas observed following intragastric or intraintestinal administrations of surface‐active alkyltrimethylammonium salts. This lack of effect upon intraintestinal or intragastric administration probably depends on an inability of the surfactants to reach the site of action when administered fro

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02406.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractEthanol in concentrations higher than 10‐2M (or about 0.5 ‰ W/W) inhibited the uptake of14C‐5‐hydroxytryptamine (serotonin) in human blood platelets in an artificial, protein‐free medium, by a noncompetitive mechanism. The inhibition was not influenced by the alcohol dehydrogenase inhibitor methylpyrazole (10‐3M). In concentrations up to 0.1M, ethanol had no effect on 5‐HT efflux from the platelets. At higher concentrations, ethanol increased efflux. Inhibition of 5‐HT uptake was found to increase progressively in the sequence methanol ‐ ethanol ‐

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02407.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

摘要:

AbstractThe effects of TCPO (trichloropropylene oxide) on the embryotoxicity and teratogenicity of styrene and styrene oxide on chick embryos were investigated. The compounds were injected into the air space of the eggs in a total volume of 25 μI on the third day of embryogenesis. TCPO increased embryotoxicity and teratogenicity of styrene and styrene oxide. Our results present evidence that the epoxides possess embryotoxic and teratogenic properties in chick embryos

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02408.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02409.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1979.tb02410.x

出版商:Blackwell Publishing Ltd    

年代:1979

数据来源: WILEY