A novel cognition enhancer NS-105 modulates adenylate cyclase activity through metabotropic glutamate receptors in primary neuronal culture

The effect of (+)-5-oxo-D-prolinepiperidinamide monohydrate (NS-105), a novel cognition enhancer, on adenylate cyclase activity was investigated in cultured neurons of the mouse cerebral cortex. NS-105 (10^–7 and 10^–6 M) inhibited forskolin-stimulated cyclic AMP formation, an action that was dependent on pertussis toxin-sensitive G proteins. Conversely, in pertussis toxin-pretreated neurons, NS-105 (10^–7 –10^–5 M) significantly enhanced the forskolin-stimulated cyclic AMP formation, and this action was completely reversed by cholera toxin. A metabotropic glutamate receptor agonist (1S, 3R)-1-aminocyclopentane-1, 3-dicarboxylic acid (1S, 3R-ACPD) produced similar bi-directional actions on the cyclic AMP formation. Both of these inhibitory and facilitatory actions of NS-105 and 1S, 3R-ACPD were blocked by L(+)-2-amino-3-phosphopropinoic acid (L-AP3). NS-105 (10^–6 M) and 1S, 3R-ACPD (10^–4 M) significantly enhanced isoproterenol- and adenosine-stimulated cyclic AMP formation. The enhancement of such Gs-coupled receptor agonists-stimulated cyclic AMP formation was also produced by quisqualate but not by L(+)-2-amino-4-phosphonobutanoate (L-AP4). The phosphoinositides hydrolysis was enhanced by 1S, 3R-ACPD (10^–4 M) but not by NS-105 (10^–6 M), however, 1S, 3R-ACPD-induced increase in phosphoinositides turnover was attenuated by NS-105. These findings suggest that NS-105 stimulates metabotropic glutamate receptor subclasses that are coupled both negatively and positively to adenylate cyclase, but it acts as an antagonist at the receptor subclasses that are linked to phosphoinositides hydrolysis. Received: 3 February 1997 / Accepted: 25 April 1997     

依那普利对离体豚鼠乳头状肌的电生理作用

目的：研究依那普利（Ｅｎａ）对豚鼠乳头状肌电生理特性，哇巴因诱发的延迟后除极（ＤＡＤ）和触发电活动（ＴＡ）的直接作用方法与结果，采用标准玻璃微电极技术记录豚鼠乳头状肌动作电位，Ｅｎａ呈浓度依赖性增加静息膜电位（ＲＰ）和动作电位幅度（ＡＰＡ），而对０期最大除极，超射，和动作电位时程无明显影响Ｅｎａ１０μｍｏｌ．Ｌ＾－１则可明显抑制哇巴因０．５μｍｏｌ．Ｌ＾－１则可明显抑制哇巴因０．５μｍｏｌ．Ｌ＾－     

近节指骨段屈肌腱鞘不同范围损伤对肌腱功能的影响

目的 探索手指屈肌腱在近节指骨段不同范围损伤时对屈指肌腱功能的影响。方法 采用12只成人尸体手指。实验分为:第一阶段屈指肌腱完整,以后四个阶段依次沿近节指骨掌侧小线闭开小央1/4、1/2、3/4及全长。在掌指关节被动屈80°和掌指关节屈80°同时近侧指关节屈100°时,测量指浅屈肌腱(FDS)和指深屈肌腱(FDP)的滑动距离。根据肌腱力臂和滑动距离的关系,得出屈指肌腱在掌指关节处和近侧指间关节及肌腱在近节指骨段的弓弦畸形程度。结果 腱鞘中央1/4切开时,指屈肌腱的滑动距离、力臂均无显著变化;1/2切开后,单纯屈曲掌指关节时的FDS腱和掌指、近节指间关节屈曲时的FDS、HDP腱的滑动距离和力臂较腱鞘完整时显苫增大(P<0.05);切开3/4长度后,FDS、FDP腱滑动距离均有统计学意义变化,FDS、FDP腱力臂平均增加8～9％;全切开腱鞘,FDS、FDP腱滑动距离变化正统计学上有高度显著性(P<0.01),两腱力臂分别增加16％和15％。随腱鞘切开范围增大,FDS、FDP在近节指骨段的弓弦畸形程度也越来越大。结论 从肌腱的生物力学变化可见,近节指骨段腱鞘的小范围损伤如中间1/4以内损伤时,对肌腱功能影响小,可以不予修复;若损伤超过1/2长度,尤其对腱鞘全长损伤,应予以修复以恢复肌腱功能。     

Antioxidant enzyme activities and total nitrite/nitrate levels in the collar model. Effect of nicardipine.

There is a large body of literature describing the causative role of oxidative stress mediated by increased levels of reactive oxygen species in the pathogenesis of cardiovascular disease such as atherosclerosis, hypertension, and restenosis after angioplasty. The positioning of a soft silicone collar around the rabbit carotid artery elicits intimal thickening. The findings from recent studies demonstrated that both intimal thickening and atherosclerosis lead to synthesis of inducible nitric oxide synthase, resulting in abundant amounts of nitric oxide. We investigated the effects of collaring and nicardipine treatment on the activities of antioxidant enzymes, superoxide dismutase and catalase, and total nitrite/nitrate levels, stable products of nitric oxide. Placing the collar increased the total nitrite/ nitrate levels and decreased superoxide dismutase activity in collared arteries. Treatment with nicardipine (20 mg/kg/day, s.c.) prevented enhanced nitric oxide degradation without affecting superoxide dismutase and catalase activities. Our results suggest that enhanced nitric oxide production and superoxide anion are generated in response to the collaring, resulting in oxidative stress within the segment in this model.     

THE BASIC CHARACTERISTICS OF THE NUCLEOTIDE SEQUENCE OF 5S RIBOSOMAL RNA FROM THE HUMAN WORM PARASITE FASCIOLOPSIS BUSKI

With the method of rapid gel sequencing, the complete nueleotide sequence of Fasciolopsis buski 5S rRNA has been determined: AAC GGG AUG AAG CUA GAC AUG UGG CGG CCU AGU UGG AGG UCG GAA CUC GGA AGU UAA GGA AUG UUG GGC CUG GUU AGU ACU GGU AUG GGU GAC CUU GGG AAU ACC GGG UGU UGC GUC CA_(OH) This have been compared with 553 species of other organisms 5S rRNA sequences previously published and fitted to a secondary structural model.     

Sevoflurane anesthesia for a patient with cerebral palsy

We report anesthetic management of a 20-year-old male patient with cerebral palsy who underwent an operation for retinal detachment of the left eye. Induction and maintenance of anesthesia were smoothly done with inhalation of 1-5% sevoflurane with nitrous oxide and oxygen. Emergence of anesthesia was also smooth except for slight and transient excitement. Anesthetic management of a patient with cerebral palsy was also discussed.