苯丙胺诱发小鼠激怒反应及其机制

苯丙胺15mg/kg ip能诱发小鼠激怒反应,使小鼠出现攻击和殴斗行为。强安定药、弱安定药和利血平有明显拮抗效果。镇静剂如巴比妥类、抗胆碱药及抗肾上腺素药均无拮抗作用。金刚胺、左旋多巴和阿扑吗啡均能增强苯丙胺的激怒效应。因苯丙胺激怒小鼠的方法简便易行,可作为筛选抗精神病药的动物模型。苯丙胺产生激怒作用的机制与增强多巴胺能神经的功能有关,推测可能是促进边缘系统多巴胺释放的结果。     

Patellofemoral joint: kinematic MR imaging to assess tracking abnormalities

The patellofemoral joint was imaged with magnetic resonance (MR) in the axial plane while the knee was positioned from 0 degrees to 32 degrees of flexion (nine positions). These multiple sequential images obtained within the early phases of flexion of the knee were viewed in a "cine-loop" format, producing a kinematic study that clearly demonstrated the relationship of the patella to the trochlear groove. Four healthy subjects and one patient with known bilateral subluxing patellae were studied. The preliminary results suggest that kinematic MR imaging of the patellofemoral joint is potentially useful for the evaluation of patellar tracking abnormalities.     

Analysis of Scottish Duchenne and Becker muscular dystrophy families with dystrophin cDNA probes.

One hundred and thirty-two Scottish families, representing the majority of currently known cases in this country with at least one living subject affected by DMD (110) or BMD (22), were studied with a series of cDNA probes excluding the 3' region of the gene (probes 10-14). Using mainly HindIII digested DNA from affected males, 89 patients showed deletions which ranged from 1 to 32 HindIII fragments in size. Two patients were also detected with exon duplications. Abnormalities were found to be particularly concentrated in the area of probe cDNA 8, with 56 patients being deleted for at least one of the fragments detected by this probe. A second smaller concentration of deletions was found with probe 1-2a which showed 16 deletions and two duplications. The endpoints of cDNA deletions or duplications were determined with a maximum variability of one HindIII fragment in 83 patients, while the remaining eight patients had a single deletion endpoint defined. The deletions found in two of our patients appear to conflict with the previously stated exon order at the 5' end of the gene. Although no specific deletion patterns were apparent for DMD, the deletions found in 13 of the BMD patients all included the most proximal (10 kb) fragment detected by probe 8.     

Histamine H1 receptor occupancy and pharmacodynamics of second generation H1-antihistamines

Summary. The predictive efficacy of drugs in humans is frequently estimated from both a high affinity for their receptor as measured in vitro and a long plasmatic half-life. This is grossly misleading since one key parameter is missing: drug concentration at the receptor site in vivo. As a case study we compared the efficacies of three H₁ antihistamines in inhibiting histamine-induced wheal and flare in humans at two different time points with the above mentioned parameters. It is concluded that estimating in vivo receptor occupancy, which takes into account both the affinity of the drug for the receptor and its free plasma concentration, is a far better predictor for human pharmacodynamics and hence antihistamine potency, than considering in vitro affinity and plasmatic half-life only. Received 2 May 2005; returned for revision 7 June 2005; accepted by M. J. Parnham 13 June 2005