Pharmacology & toxicology最新文献_第8页

Beta,gamma-methylene ATP but not alpha,beta-methylene ATP mimics the inhibitory effect of ATP on ventricular automaticity. -亚甲基ATP而非-亚甲基ATP模拟ATP对心室自动性的抑制作用。

Pharmacology & toxicology Pub Date : 2000-02-01 DOI: 10.1034/j.1600-0773.2000.d01-13.x

J Hernández, M L Laorden, F Ruiz, J A Ribeiro

引用次数: 0

Toxicity study of di(2-ethylhexyl)phthalate (DEHP) in combination with acetone in rats. 邻苯二甲酸二(2-乙基己基)酯与丙酮联用对大鼠的毒性研究。

Pharmacology & toxicology Pub Date : 2000-02-01 DOI: 10.1034/j.1600-0773.2000.d01-17.x

M Dalgaard, G Ostergaard, H R Lam, E V Hansen, O Ladefoged

{"title":"Toxicity study of di(2-ethylhexyl)phthalate (DEHP) in combination with acetone in rats.","authors":"M Dalgaard, G Ostergaard, H R Lam, E V Hansen, O Ladefoged","doi":"10.1034/j.1600-0773.2000.d01-17.x","DOIUrl":"https://doi.org/10.1034/j.1600-0773.2000.d01-17.x","url":null,"abstract":"In two separate studies with exposure duration 9 weeks or 4 weeks, male Wistar rats were dosed with di(2-ethylhexyl)phthalate (DEHP) by gavage and exposed to drinking water with or without acetone (0.5% wt/v in the 9-week study, 1.0% wt/v in the 4-week study). In the 9-week study the doses of DEHP were 0, 125, 250, 500 or 1000 mg/kg b.wt. In the 4-week study the doses of DEHP were increased to 1000, 5000 and 10,000 mg/kg b.wt. In the 9-week study, the relative liver weight was increased in the rats exposed to 500 and 1000 mg/kg b.wt. No interaction of DEHP and acetone was observed in any of the measured parameters. In the 4-week study DEHP, at the highest dose level, resulted in severe general toxicity. The group exposed to DEHP in combination with acetone was more affected. Male fertility was decreased. Body weight was decreased, and the relative weight of the liver, kidney, heart, brain and adrenals increased. The relative weight of the testes decreased in the 5000 and 10,000 mg/kg b.wt. groups. The weight of seminal vesicles and epididymals decreased at 10,000 mg/kg b.wt. In animals exposed to 5000 and 10,000 mg DEHP/kg b.wt. a severe atrophy of the seminiferous tubules and a slight diffuse Leydig's cell hyperplasia was observed. The cellular debris and conglomerates of desquamated cells found in the lumen of the seminiferous tubules were immunostained positive for vimentin. This indicates that Sertoli cell cytoplasm is included in the conglomerates an interesting finding not previously described. No specific interaction of DEHP and acetone was observed in any of the measured parameters.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"86 2","pages":"92-100"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21580208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 39

The influence of the nitric oxide synthase inhibitor L-NOARG on the effects of ethanol in rats after acute ethanol administration. 一氧化氮合酶抑制剂L-NOARG对大鼠急性给药后乙醇作用的影响。

Pharmacology & toxicology Pub Date : 2000-02-01 DOI: 10.1034/j.1600-0773.2000.d01-12.x

V Vassiljev, I Mesila, M Väli, P Pokk

{"title":"The influence of the nitric oxide synthase inhibitor L-NOARG on the effects of ethanol in rats after acute ethanol administration.","authors":"V Vassiljev, I Mesila, M Väli, P Pokk","doi":"10.1034/j.1600-0773.2000.d01-12.x","DOIUrl":"https://doi.org/10.1034/j.1600-0773.2000.d01-12.x","url":null,"abstract":"The aim of this work was to study the effects of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine (L-NOARG) on the sedative and toxic effects of ethanol in rats. Ethanol at a dose of 3 g/kg, intraperitoneally induced sleep in rats (sleep time: 111.2+/-10.3 min.). Administration of the nitric oxide synthase inhibitor L-NOARG (20 and 40 mg/kg, intraperitoneally) 30 min. before ethanol significantly increased the duration of ethanol-induced sleep. L-NOARG at doses of 20 and 40 mg/kg reduced the exploratory activity of rats in the open-field test and significantly enhanced the sedative effect of ethanol in this test. It is possible that this effect is not caused by the interaction of ethanol with nitric oxide pathways but by synergistic CNS depression caused by ethanol and L-NOARG. L-NOARG (20 and 40 mg/kg) had no effect on ethanol concentrations in blood after acute ethanol administration (2 and 3 g/kg). Moreover, the combined administration of ethanol (2 g/kg) and L-NOARG (20 and 40 mg/kg) caused a decrease in the body weight of animals, observed for 14 days. Also, livers of these rats were studied for necrosis and connective tissue reaction. In histological studies L-NOARG at a dose of 40 mg/kg had no effect on hepatic necrosis caused by the acute administration of ethanol but strengthened connective tissue reaction. L-NOARG is widely used in pharmacological studies, including those concerning the effects of ethanol. However, on the basis of our data the possibility of toxic interactions with ethanol should be considered.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"86 2","pages":"63-7"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21580203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Effect of loperamide on mucosal guanylyl cyclase activity in rat jejunum following Escherichia coli heat-stable toxin-induced fluid accumulation. 洛哌丁胺对大肠杆菌热稳定性毒素引起的液体积聚后大鼠空肠粘膜观乙酰环化酶活性的影响。

Pharmacology & toxicology Pub Date : 2000-02-01 DOI: 10.1034/j.1600-0773.2000.d01-15.x

U M Farack, A Asher, B Elsenhans, B Schütte-Lückenga, R Gerzer

{"title":"Effect of loperamide on mucosal guanylyl cyclase activity in rat jejunum following Escherichia coli heat-stable toxin-induced fluid accumulation.","authors":"U M Farack, A Asher, B Elsenhans, B Schütte-Lückenga, R Gerzer","doi":"10.1034/j.1600-0773.2000.d01-15.x","DOIUrl":"https://doi.org/10.1034/j.1600-0773.2000.d01-15.x","url":null,"abstract":"Loperamide has antidiarrhoeal activities against secretagogues with different mechanisms of action. Besides its opioid-like effect on intestinal motility and secretion it might exhibit additional antisecretory properties which may not be completely elucidated yet. Direct effects of loperamide on mucosal guanylyl cyclase have never been observed. We therefore investigated the effect of loperamide on intestinal fluid transport altered by heat-stable Escherichia coli enterotoxin which acts by stimulating mucosal guanylyl cyclase. Net fluid movement was determined during a 1 hr incubation period in ligated jejunal loops of anaesthetised female Wistar rats. Transport rates of net fluid movement were calculated from the loop contents measured gravimetrically at the beginning and the end of the experiments. Addition of heat-stable Escherichia coli enterotoxin to the luminal solution resulted in a net secretion of water which was significantly reversed into net absorption by loperamide. The specific activity of the particulate guanylyl cyclase was determined in mucosal scrapings of the jejunum without and with the addition of heat-stable Escherichia coli enterotoxin and/or loperamide. Additions of loperamide of up to 10 micromol/l did not change guanylyl cyclase activity. We conclude that the effect of loperamide counteracting heat-stable Escherichia coli enterotoxin induced changes of intestinal fluid transport does not involve a direct effect on guanylyl cyclase.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"86 2","pages":"78-82"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21580206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Cyclic adenosine monophosphate inhibits ursolic acid-induced apoptosis via activation of protein kinase A in human leukaemic HL-60 cells. 单磷酸环磷酸腺苷通过激活人类白血病 HL-60 细胞中的蛋白激酶 A 抑制熊果酸诱导的细胞凋亡。

Pharmacology & toxicology Pub Date : 2000-02-01 DOI: 10.1034/j.1600-0773.2000.d01-10.x

B M Choi, R Park, H O Pae, J C Yoo, Y C Kim, C D Jun, B H Jung, G S Oh, H S So, Y M Kim, H T Chung

{"title":"Cyclic adenosine monophosphate inhibits ursolic acid-induced apoptosis via activation of protein kinase A in human leukaemic HL-60 cells.","authors":"B M Choi, R Park, H O Pae, J C Yoo, Y C Kim, C D Jun, B H Jung, G S Oh, H S So, Y M Kim, H T Chung","doi":"10.1034/j.1600-0773.2000.d01-10.x","DOIUrl":"10.1034/j.1600-0773.2000.d01-10.x","url":null,"abstract":"This study was designed to investigate the effect of cAMP on ursolic acid-induced apoptosis of HL-60 cells. Ursolic acid decreased the viability of the cells in a dose-dependent manner, which was revealed as an apototic process characterized by ladder-pattern DNA fragmentation in agarose gel electrophoresis and segmented nuclei in DAPI-sulpharhodamin 101 staining. Ursolic acid-induced apoptosis of the cells was markedly inhibited by the addition of cAMP-elevating agents including DB-cAMP, CPT-cAMP, 8-Br-cAMP and forskolin. These results were further evidenced by the fact that inhibitors of cAMP-dependent protein kinase including H89 and KT5720 completely inhibited the cAMP-mediated rescue of HL-60 cells from ursolic acid-induced apoptosis. In addition, differentiating agents of the cells such as dimethyl sulfoxide and retinoic acid did not affect the ursolic acid-induced apoptosis of HL-60 cells. These results suggest that signaling pathway of cAMP-dependent activation of protein kinase A may affect the responsiveness of tumor cells upon ursolic acid.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"86 2","pages":"53-8"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21580267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 37

Effects of anticonvulsants on local anaesthetic-induced neurotoxicity in rats. 抗惊厥药对大鼠局部麻醉神经毒性的影响。

Pharmacology & toxicology Pub Date : 2000-02-01 DOI: 10.1034/j.1600-0773.2000.d01-11.x

K Sawaki, K Ohno, K Miyamoto, S Hirai, K Yazaki, M Kawaguchi

{"title":"Effects of anticonvulsants on local anaesthetic-induced neurotoxicity in rats.","authors":"K Sawaki, K Ohno, K Miyamoto, S Hirai, K Yazaki, M Kawaguchi","doi":"10.1034/j.1600-0773.2000.d01-11.x","DOIUrl":"https://doi.org/10.1034/j.1600-0773.2000.d01-11.x","url":null,"abstract":"The effects of various anticonvulsants on local anaesthetics procaine- and lidocaine-induced convulsions were investigated in rats. Pretreatment with diazepam (2.5-5 mg/kg, intraperitoneally) and clonazepam (5-10 mg/kg, intraperitoneally) completely protected the rats against both local anaesthetic-induced convulsions. Phenobarbital (12.5-50 mg/kg, subcutaneously) also significantly decreased the incidence of both convulsions and prolonged their latencies. Carbabazepine (10-40 mg/kg, intraperitoneally) did not completely repress both convulsions, but it prolonged their latencies. Phenytoin (5-20 mg/kg, intraperitoneally) and primidone (30-60 mg/kg, intraperitoneally) markedly enhanced both local anaesthetic-induced convulsions, as shown by shortening of latency and increase in mortality. Valproate (100-200 mg/kg, intraperitoneally) produced a protective effect against procaine-induced convulsions, while it strongly enhanced lidocaine-induced convulsions. These results suggest that the benzodiazepines are effective drugs to prevent neurotoxicity induced by local anaesthetics, while phenytoin and primidone potentiate them.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"86 2","pages":"59-62"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21580268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 29

New safe medicines faster: A proposal for a key action within the European union's 6th framework programme. 更快地开发新的安全药物:欧盟第六个框架规划内的一项关键行动建议。

Pharmacology & toxicology Pub Date : 2000-01-01

O J Bjerrum

{"title":"New safe medicines faster: A proposal for a key action within the European union's 6th framework programme.","authors":"O J Bjerrum","doi":"","DOIUrl":"","url":null,"abstract":"The global competitiveness of the European pharmaceutical industry is under threat. Technology currently available for the development of new medicines is unable to match the pace of drug discovery and design; and the ever-growing demand for safety, efficacy and quality documentation has increased the cost and time involved in getting new medicines on the market. Although the pharmaceutical industry is one of the strongest in Europe in terms of research, innovation, exports and employment, there are severe restrictions on its ability to create wealth and launch safe drugs for the treatment of common and rare afflictions. The present situation should not be allowed to continue. For this reason, the European Federation for Pharmaceutical Sciences (EUFEPS) has proposed a key action under the title \"New safe medicines faster\" for the forthcoming EU 6th RTD framework programme. The key action has three main objectives: to seek new technologies capable of more effective selection of potential drug candidates for innovative medicines while accommodating safety demands; to use such technologies to speed up the pharmaceutical development process and eliminate bottlenecks created by initial exploratory drug research; and to cultivate a pan-European interdisciplinary network that bridges the gap between industry, academia and regulatory authorities. By involving regulatory authorities early on and fuelling research and innovation with EU money it should be possible to create a new set of recognised European standards whereby new safe medicines can be brought onto the market faster and cheaper.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"86 Suppl 1 ","pages":"23-6"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21745734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of omega-conotoxin GVIA on noradrenaline release from postganglionic sympathetic neurones in rabbit aorta. omega- concontoxin GVIA对兔主动脉节后交感神经元去甲肾上腺素释放的影响。

Pharmacology & toxicology Pub Date : 2000-01-01

O A Nedergaard

{"title":"Effect of omega-conotoxin GVIA on noradrenaline release from postganglionic sympathetic neurones in rabbit aorta.","authors":"O A Nedergaard","doi":"","DOIUrl":"","url":null,"abstract":"The aim of the present work was to examine the effect of the selective N-type calcium blocking agent omega-conotoxin GVIA on stimulation-evoked release of noradrenaline from sympathetic nerves in rabbit isolated aorta with regard to stimulation frequency, extracellular Ca2+ concentration, and transmitter uptake. Rings of rabbit isolated aorta were preloaded with (-)-3H-noradrenaline and the fractional 3H-overflow evoked by electrical-field stimulation was determined by liquid scintillation spectrometry. Omega-conotoxin GVIA (3 x 10(-10)-3 x 10(-8) M) did not alter the spontaneous 3H-outflow. Omega-conotoxin GVIA (3 x 10(-10)-3 x 10(-8) M) caused a slowly developing reduction of stimulation-evoked 3H-overflow at 1 and 30 Hz. The Emax for the omega-conotoxin-induced inhibition was less (70%) at 30 Hz than that (96%) seen at 1 Hz. Short-term incubation with omega-conotoxin GVIA caused a subsequent steady-state inhibition. The inhibitory action of omega-conotoxin GVIA (3 x 10(-10)-3 x 10(-9) M) was inversely related to the extracellular Ca2+ concentration (6.5 x 10(-4)-2.7 x 10(-3) M). Cocaine (3 x 10(-5) M) plus corticosterone (4 x 10(-5) M), neuronal and extraneuronal uptake inhibitors, respectively, did not alter the inhibitory effect of omega-conotoxin GVIA (3 x 10(-9) M) on 3H-overflow evoked by stimulation at a frequency of either 1 or 30 Hz. It is concluded that omega-conotoxin GVIA acts on prejunctional N-type calcium channels to inhibit stimulation-evoked noradrenaline release from sympathetic neurone terminals in rabbit aorta. At a high frequency, another subtype calcium channel may possibly be involved. The action of omega-conotoxin GVIA is independent of neuronal and extraneuronal uptake mechanisms for noradrenaline, but dependent on the amount of Ca2+ to be transported across the neurilemma from the extracellular space into the neurone.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"86 1","pages":"30-5"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21572130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The influence of repeated prestressors on single stress response in rats. 反复应激对大鼠单次应激反应的影响。

Pharmacology & toxicology Pub Date : 2000-01-01

A Yamamotová, M Starec, H Rasková, R Rokyta

{"title":"The influence of repeated prestressors on single stress response in rats.","authors":"A Yamamotová, M Starec, H Rasková, R Rokyta","doi":"","DOIUrl":"","url":null,"abstract":"The effect of various stressors of different intensity applied in random order before the final single immersion restraint stress was tested in two inbred rat strains, isoprenaline-sensitive and isoprenaline-resistant. The isoprenaline-sensitive strain revealed higher incidence of heart lesions after this single acute stress and low incidence of gastric lesions. The isoprenaline-resistant strain had the opposite characteristics. These differences were constantly reproducible when this strong stressor was used. After prestress by different stressors (tail-flick, ether anaesthesia, Porsolt swimming stress) at different time schedules, the incidence of gastric ulcer lesions, the weight of organs (heart, adrenals, spleen) changed substantially in isoprenaline-sensitive rats only. The most important result was reversal of the extent of gastric lesions. The isoprenaline-sensitive strain revealed more lesions than the isoprenaline-resistant one. The repeated different prestressors mainly changed the reactivity of animals, isoprenaline-sensitive rats becoming more similar to isoprenaline-resistant rats. These findings urged us to interpret carefully the results obtained in stress research with different and multiple stressors both in animals and humans.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"86 1","pages":"8-15"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21572127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

10th Porto Meeting on Adrenergic Mechanisms. Porto, Portugal, September 25-27, 2000. Abstracts. 第十届波尔图肾上腺素能机制会议。波尔图，葡萄牙，2000年9月25-27日。摘要。

Pharmacology & toxicology Pub Date : 2000-01-01

引用次数: 0