Inhibitory effects of benzoate on chiral inversion and clearance of N(G)-nitro-arginine in conscious rats.

N(G)-nitro-arginine (NNA) is known to exhibit stereoselective pharmacokinetics in which N(G)-nitro-d-arginine (d-NNA) has a faster clearance rate than N(G)-nitro-l-arginine (l-NNA) in anesthetized rats, and d-NNA undergoes unidirectional chiral inversion. It was postulated that chiral inversion of d-NNA was performed in a two-step pathway by d-amino acid oxidase (DAAO) followed by an unidentified transaminase. Such chiral inversion contributes (at least partially) to the pharmacokinetic stereoselectivity of NNA. This study used the selective inhibitor of DAAO, sodium benzoate, to test the above hypothesis. An i.v. bolus injection of d-NNA (32 mg/kg) and l-NNA (16 mg/kg) in conscious rats exhibited biphasic disposition with different pharmacokinetic parameters in a stereospecific manner (approximately 5-10-fold differences). Unidirectional chiral inversion of d-NNA but not l-NNA was found from these animals. In addition to its similar inhibitory effects on the d-NNA conversion and DAAO activity in kidney homogenates, sodium benzoate completely blocked chiral inversion of d-NNA and led to a smaller stereospecific difference, reflected by a nearly 50% reduction of d-NNA clearance and a 2-fold increase in t(1/2) and area under the curve of d-NNA in benzoate-pretreated rats. The results suggest that DAAO plays an essential role in chiral inversion of d-NNA and chiral inversion contributes mostly to the pharmacokinetic stereospecificity of NNA.     

椎间盘镜系统治疗腰椎间盘突出症550例

目的探讨椎间盘镜系统治疗腰椎间盘突出症的疗效. 方法改进部分手术器械,采用膝胸坐位,穿刺黄韧带进入椎管等方法,应用METRx进行腰椎间盘取出术550例. 结果随访6～36个月,平均21个月,疗效参考Nakai标准,优478例 (86.9%),良60例(10.9%),可6例(1.1%),差6例(1.1%).疗效差6例再次镜下扩大侧隐窝清理残留髓核疗效转良. 结论 METRx下行腰椎间盘取出术,创伤小、安全、疗效好,值得推广.     

备劳特联合爱喘乐雾化吸入治疗儿童哮喘急性发作的疗效观察

目的 :观察氧雾化吸入备劳特和爱喘乐治疗儿童哮喘急性发作的疗效。方法 :选择 15 8例哮喘急性发作患儿作为研究对象 ,分为观察组和对照组。观察组采用氧驱动雾化吸入备劳特和爱喘乐 ;对照组静脉滴注氨茶碱和地塞米松。结果 :观察组显效率 87.3% (96 /110 ) ,总有效率 99.1% (10 9/110 ) ,临床治愈率 94 .5 % (10 4 /110 ) ;对照组显效率 2 2 .9% (11/48) ,总有效率 6 0 .4 % (2 9/48) ,临床治愈率 5 4 .2 % (2 6 /48)。观察组显效率、总有效率及临床治愈率皆显著高于对照组 ,差异有高度统计意义 (P <0 .0 1)。观察组治疗后心率较治疗前明显下降 ,差异有统计意义(P <0 .0 5 )。结论 :采用氧驱动雾化吸入备劳特和爱喘乐能快速、有效地控制哮喘发作。     

原发性软骨肉瘤CT诊断2例

软骨肉瘤的X线诊断已有较多研究,但软骨肉瘤的CT诊断较少研究,为此,提供经穿刺活检病理证实的软骨肉瘤2例,以提高对软骨肉瘤的CT诊断水平。病例1男,52岁。左肩关节疼痛、活动受限10年余,加重半年。查体:左肩关节活动受限、僵直,不能抬举。实验室检查:碱性磷酸酶增高。CT表现:左肱骨、干骺端骨质破坏,病变上下连续约6·0cm,中心呈大囊状,周围呈小囊状,破坏区中见1·5cm×1·5cm的不规则高密度灶,肱骨外侧骨皮质不连续,向周围软组织侵犯,形成软组织肿块,肿块内钙化灶呈斑块状。无骨膜反应,肩关节间隙可,关节面未见侵犯(图1)。CT诊断:①左…     

Glutamate acts at NMDA receptors on fresh bovine and on cultured human retinal pigment epithelial cells to trigger release of ATP

Efficient vesicle membrane recycling at presynaptic terminals is pivotal for preventing depletion and maintaining high firing rates in neuronal networks. We used a new approach, based on the combination of spectrally different optical probes, to investigate how stimulation determines the fate of synaptic vesicles after endocytosis. We found that in the small central synapses of rat hippocampal neurones low frequency stimulation (40 action potentials at 2 Hz) targets vesicles preferentially to vesicle pools that were kinetically faster. Vesicles taken up during endocytosis triggered by high frequency stimulation (400 action potentials, 20 Hz) were also placed in the back of the release queue. We performed a spatial analysis of the recycled vesicles in living hippocampal boutons using two spectrally different FM-dyes (FM1-43 and FM5-95). By using these consecutively, vesicles endocytosed by either stimulation protocol were labelled with a different colour. This revealed that the kinetic arrangement was also reflected in the spatial organization of vesicles within the bouton. Next, we identified the postsynaptic site of the active zone by transfecting the neurones with postsynaptic density protein PSD-95-CFP. The data from these triple colour experiments suggest that retrieval after low frequency stimulation keeps vesicles in a more confined region closer to the active zone as identified by PSD-95-CFP expression at the postsynaptic site.     

立体着床模型--小鼠囊胚与子宫内膜的共培养

目的:建立小鼠囊胚体外着床的三维模型,为着床机制的研究提供重要工具.方法:将小鼠囊胚与其自身子宫内膜分别共培养在空气、含500,750和950 mL/L O2的混合气体与组织培养液的气液界面上,比较不同O2浓度下小鼠囊胚的贴附率,确定体外共培养的最佳O2浓度;同时将确认有囊胚贴附的子宫内膜取出作HE染色.结果:不同O2浓度下,囊胚的贴附率分别为64.75%,47.86%,42.37%和30.97%,x2检验提示其差异有显著性(x2=28.145,P=0.000);且随着混合气体中O2浓度的逐渐升高,囊胚贴附率呈逐渐降低趋势.因此50 mL/L CO2 950 mL/L空气对囊胚与子宫内膜的共培养是最有利的;同时,囊胚贴附子宫内膜后并无扩展行为而是直接侵入子宫内膜.结论:50 mL/L CO2 950 mL/L空气最有利于囊胚与子宫内膜的共培养;且囊胚贴附子宫内膜后不发生外延生长,而是直接侵入子宫内膜.本实验成功地建立了小鼠囊胚体外着床的三维模型.     

Nerve growth factor and tyrosine kinase A in human salivary adenoid cystic carcinoma: expression patterns and effects on in vitro invasive behavior.

PURPOSE: Perineural invasion is a frequent occurrence in salivary adenoid cystic carcinoma (ACC) and may prevent complete surgical resection. Studies have indicated that nerve growth factor (NGF) and its high-affinity receptor tyrosine kinase A (TrkA) may play a role in perineural invasion in several malignancies in which perineural invasion is observed. The present study was conducted to investigate the expression of NGF and TrkA in salivary ACC and to examine the effects of NGF on adhesion, migration and invasion capacities of a salivary ACC cell line (SACC-83) in vitro. PATIENTS AND METHODS: Expression of NGF and TrkA was explored using immunohistochemistry in paraffin-embedded tissues of 32 cases of salivary ACC. The effects of NGF on in vitro adhesion, migration, and invasion capacities of the SACC-83 cell line were examined using an MTT assay and a modified Boyden chamber assay respectively. RESULTS: In ACC specimens, 31 (96.9%) and 32 (100%) tumors showed immunoreactivity for NGF and TrkA respectively. Significant correlations were found between NGF/TrkA expression levels and perineural invasion (P < .05). In cell adhesion assay, the percent adherences of SACC-83 cells co-cultured with 25 ng/ml NGF at 1.5 hours and 5, 25 ng/ml NGF at 6 hours were significantly higher than that co-cultured with 0 ng/ml NGF (P < .05). However, high concentration of NGF (500 ng/ml) resulted in a significant inhibition of invasion (P < .05). CONCLUSION: Overexpression of NGF and TrkA in human salivary ACC tissues may constitute a reason for perineural invasion in salivary ACC.     

清胆汤治疗慢性胆囊炎52例

近3年来，笔者自拟清胆汤治疗慢性胆囊炎52例收到较好效果，现报告如下。     

Brain natriuretic peptide enhances the endothelium-independent cAMP and vasorelaxant responses of calcitonin gene-related peptide in rat aorta

Calcitonin gene-related peptide (CGRP) causes vasorelaxation in rat aorta involving endothelium/nitric oxide (NO)-dependent elevations of both cAMP and cGMP levels. When endothelium is removed, preincubation with exogenous NO uncovers and potentiates direct (endothelium-independent) cAMP elevations and vasorelaxations caused by CGRP. This enhancing effect of NO potentially involves elevation of cGMP and inhibition of Type III (cGMPinhibitable) phosphodiesterase, causing accumulation of cAMP. However, NO may have other actions. The aim of the present study was to determine if brain natriuretic peptide (BNP), which elevates cGMP levels independent of NO, could enhance cAMP accumulations and vasorelaxations induced by CGRP in rat aortic rings denuded of endothelium. When added separately, neither CGRP (100 nM) nor BNP (10 nM) altered cAMP levels. When added in combination, CGRP (100 nM) and BNP (10 nM) significantly elevated cAMP levels (from control of 0.95 ± 0.08 to 1.53 ± 0.09 pmol/mg protein) at 2 min. BNP (10 nM) elevated cGMP levels 10-fold at 2 min and this response was not altered by co-administration of CGRP (100 nM).Pretreatment with BNP at concentrations as low as 1 nM in endothelium-denuded aortic rings greatly enhanced the direct vasorelaxant effects of CGRP (100 nM) (from control of 0% to 57.6 ± 6.8% relaxation of phenylephrineprecontractions). Our findings indicate that BNP enhances direct (endothelium-independent) cAMP elevations and vasorelaxations caused by CGRP in rat aorta, thus supporting the concept that cGMP inhibits cAMP metabolism and enhances CGRP-induced responses in aortic smooth muscle cells.