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11.
The pharmacological profile of the two 5-HT(3) (5-hydroxytryptamine) receptor antagonists, the putative anxiolytics ICS 205-930 and GR38032F was compared with that of diazepam in four standard behavioural tests in rats. All the investigated drugs induced an anxiolytic effect in the passive avoidance test, having reduced the latency to re-enter the chamber previously associated with an inescapable footshock, and increased the time spent in that chamber. On the basis of the lowest effective dose, both ICS 205-930 and GR38032F were about 20 times more potent than diazepam, though the anxiolytic activity of either 5- HT(3) receptor antagonist was confined to a narrow dose range (ICS 205-930: 93.7-187.5 μg/ kg, GR38032F: 125-375 μg/kg), their higher doses having been ineffective. The anxiolytic effect of diazepam, but not of ICS 205-930, was abolished by flumazenil. In contrast to diazepam, neither ICS 205-930 nor GR38032F-both given in doses up to 20 mg/kg-showed any activity in the pentylenetetrazol-induced seizures, open field, and rota-rod tests. These results suggest that the 5-HT(3) receptor antagonists may represent a new class of anxiolytic drugs devoid of anticonvulsant, sedative or muscle-relaxant properties, and that their anxi olytic activity is not mediated by benzodiazepine receptors. 相似文献
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In the symptomatic treatment of mild to moderately severe dementia associated with Alzheimer's disease, donepezil (E2020) has been introduced for the inhibition of acetylcholinesterase activity in the human brain. However, there is no morphological evidence as to how this chemical agent affects the acetylcholinesterase-positive structures in the various areas of the human and the rat CNS. This study demonstrates by histochemical means that donepezil exerts a dose-dependent inhibitory effect in vitro on acetylcholinesterase activity. The most sensitive areas were the cortex and the hippocampal formation. Within the different layers of the cortex, the cholinoceptive acetylcholinesterase-positive postsynaptic pyramidal cell bodies were more sensitive than the presynaptic cholinergic axonal processes. In the cortex, the cell body staining was already abolished by even 2 x 10(-8)M donepezil, whereas the axonal staining could be eliminated only by at least 5 x 10(-8)M donepezil. In the hippocampus, the axonal acetylcholinesterase reaction end-product was eliminated by 5 x 10(-7)M donepezil. The most resistant region was the putamen, where the staining intensity was moderately reduced by 1 x 10(-6)M donepezil. In the rat brain, the postsynaptic cholinoceptive and presynaptic cholinergic structures were inhibited by nearly the same dose of donepezil as in the human brain. These histochemical results provide the first morphological evidence that, under in vitro circumstances, donepezil is not a general acetylcholinesterase inhibitor in the CNS, but rather selectively affects the different brain areas and, within these, the cholinoceptive and cholinergic structures. The acetylcholinesterase staining in the nerve fibers (innervating the intracerebral blood vessels of the human brain and the extracerebral blood vessels of the rat brain) and at the neuromuscular junction in the diaphragm and gastrocnemius muscle of rat, was also inhibited dose dependently by donepezil.It is concluded that donepezil may be a valuable tool with which to influence both the pre- and the postsynaptic acetylcholinesterase-positive structures in the human and rat central and peripheral nervous systems. 相似文献
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Identification of two point mutations and a one base deletion in exon 19 of the dystrophin gene by heteroduplex formation 总被引:3,自引:0,他引:3
Prior Thomas W.; Papp Audrey C.; Snyder Pamela J.; Burghes Arthur H.M.; Sedra Mary S.; Western Lorraine M.; Bartello Claire; Mendell Jerry R. 《Human molecular genetics》1993,2(3):311-313
Two thirds of the Duchenne muscular dystrophy population haveeither gene deletions or duplications. The nondeletion/duplicationcases are most likely the result of point mutations or smalldeletions and duplications that cannot be easily identifiedby current strategies. The major obstacle in identifying smallmutations is due to the large size of the dystrophin gene. Weselectively screened 5 DMD exons containing CpG dinucleotidesin 110 DMD patients without detectable deletions or duplications.Nonsenses mutations are frequently due to a C- to -T transitionwithin a CG dinucleotide pair. To screen for the nonsense mutations,we used the heteroduplex method. Utilizing this approach, weidentified 2 different nonsense mutations and a single basedeletion all occurring in exon 19. This is the first reportof a clustering of small mutations in the the dystrophin gene. 相似文献
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Koumans EH Black CM Markowitz LE Unger E Pierce A Sawyer MK Papp JR 《Journal of clinical microbiology》2003,41(4):1507-1511
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Characterization of translational frame exception patients in Duchenne/Becker muscular dystrophy 总被引:8,自引:3,他引:8
Winnard Alissa V.; Klein Christopher J.; Coovert Daniel D.; Prior Thomas; Papp Audrey; Snyder Pamela; Bulman Dennis E.; Ray Peter N.; McAndrew Patricia; King Wendy; Moxley Richard T.; Mendell Jerry R.; Burghes Arthur H.M. 《Human molecular genetics》1993,2(6):737-744
The clinical progression of Duchenne muscular dystrophy (DMD)patients with deletions can be predicted in 93% of cases bywhether the deletion maintains or disrupts the translationalreading frame (frameshift hypothesis). We have identified andstudied a number of patients who have deletions that do notconform to the translational frame hypothesis. The most commonexception to the frameshift hypothesis is the deletion of exons3 to 7 which disrupts the translational reading frame. We identifieda Becker muscular dystrophy (BMD) patient, an intermediate,and a DMD patient with this deletion. In all three cases, dystrophinwas detected and localized to the membrane. One DMD patientwith an inframe deletion of exons 418 produced no dystrophin.One patient with a mild intermediate phenotype and a deletionof exon 45, which shifts the reading frame, produced no dystrophin.Two patients with large inframe deletions had discordant phenotypes(exons 341, DMD; exons 1348, BMD), but both produceddystrophin that localized to the sarcolemma. The DMD patient,113, indicates that dystrophin with an intact carboxy terminuscan be produced in Duchenne patients at levels equivalent tosome Beckers. The dystrophin analysis from these patients, togetherwith patients reported in the literature, indicate that morethan one domain can localize dystrophin to the sarcolemma. Lastely,the data shows that although most patients show correlationof clinical severity to molecular data, there are rare patientswhich do not conform. 相似文献
19.
Mria Vastag Tams Papp Zsolt Kasza Csaba Vgvlgyi 《Journal of clinical microbiology》1998,36(7):2153-2156
Nineteen Rhizomucor miehei and Rhizomucor pusillus isolates were assayed for their ability to utilize 87 various substrates as a single carbon source. Besides a difference in sucrose utilization, distinctive differences were found in the utilization of glycine, phenylalanine, and β-alanine. Five isoenzyme systems also proved useful for the determination of markers of distinctive value at a species level. Data were used to obtain information about the genetic polymorphism of these species: a high degree of variability was found among the R. pusillus isolates, whereas the group of R. miehei isolates was more homogeneous genetically. 相似文献
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