Regulation of glucose and insulin release following acute and repeated treatment with the synthetic galanin analog NAX-5055

The neuropeptide galanin is widely expressed in both the central and peripheral nervous systems. However there is limited understanding of how individual galanin receptor (GalR1, 2, and 3) subtypes mediate the physiological activity of galanin in vivo. To address this issue we utilized NAX-5055, a systemically available, metabolically stable galanin analog. NAX-5055 displays a preference for GalR1 receptors and possesses potent anticonvulsant activity in vivo, suggesting that NAX-5055 engages central galanin receptors. To determine if NAX-5055 also modulates the activity of peripheral galanin receptors, we evaluated the effect of NAX-5055 on blood glucose and insulin levels in mice. Acute and repeated (once daily for four days) systemic administration of NAX-5055 (4 mg/kg) significantly increased blood glucose levels compared to vehicle treated mice. However, a hyperglycemic response was not observed following systemic administration of NAX-805-1, a scrambled analog of NAX-5055, with critical receptor binding residues, Trp² and Tyr⁹, reversed. These results suggest that chemical modifications independent of the galanin backbone of NAX-5055 are not responsible for the hyperglycemic response. The effect of NAX-5055 on glucose homeostasis was further evaluated with a glucose tolerance test (GTT). Mice administered either acute or repeated (once daily for four days) injections of NAX-5055 (4 mg/kg) displayed impaired glucose handling and reduced insulin response to an acute glucose (1g/kg) challenge. Here we have shown that systemic administration of a centrally active GalR1-preferring galanin analog produces acute hyperglycemia and an inhibition of insulin release in vivo and that these effects are not attenuated with repeated administration. NAX-5055 thus provides a new pharmacological tool to further the understanding of function of both central and peripheral GalR1 receptors in vivo.     

p14ARF、E2F-1与肺癌

p14ARF基因和核转录因子E2F-1在细胞周期调控，细胞凋亡和肿瘤发生中具有重要作用。近年来，有研究表明p14ARF在肺癌中的表达率低于正常组织，E2F-1的表达率高于正常组织。本文将就p14ARF、E2F-1与肺癌的关系进行综述。     

Graves病介入栓塞治疗的病理研究

目的观察Graves病栓塞后的甲状腺组织动态病理变化。方法15例甲状腺动脉150 mm聚乙烯醇（PVA）微粒及平阳霉素栓塞治疗的Graves病患者,于术前、术后7天、3个月、6个月、1年、3年分别行甲状腺穿刺活检,共行44次穿刺活检,其中动脉栓塞术前15例、栓塞术后7天2例、3个月3例、6个月6例、1年5例次、3年13例次。结果栓塞后7天主要表现为凝固性坏死;栓塞后3-6个月表现为纤维组织增生变性和淋巴细胞浸润,滤泡灶性坏死为主;栓塞后1-3年主要表现为间质纤维组织增生明显和滤泡萎缩,部分散在增生滤泡被纤维间质分隔包裹,难以形成腺小叶结构,滤泡周围血管网减少。结论经甲状腺动脉栓塞治疗Graves病,甲状腺组织的病理变化是在栓塞后近期内主要表现为急性缺血坏死,然后表现为持续的慢性炎性破坏、滤泡萎缩、部分滤泡增生被明显增生的纤维组织分隔包裹的变化过程。提示微循环栓塞能肯定地破坏甲状腺组织,达到治疗Graves病较好的疗效。     

我省医学临床教学基地建设的现状与思考

对我省医学临床教学基地评审结果进行分析，就大部分基地教学意识不强、教学设施不完善、教学条件有待改善、师资队伍素质水平不高等问题进行了阐述，并针对存在的问题提出建议和思考，从建章立制规范管理、加强建设、提供保障、重视培训、提高素质、强化管理、创新机制等方面进行探索，希望能使我省医学临床教学基地质量得以提高、完善，为我省培养一流的医学专业人才奠定基础．     

正常成人脑外段视神经的MRI研究

目的 评价正常成人视神经-眼平面(NOP)视交叉以外段颅神经的MRI表现,建立正常标准。方法 随机选择正常成人志愿者50例,采用GB1.5T MR/i echo spood plus超导型磁共振成像仪及相控阵头线圈,成像序列包括自旋回波T1加权成像(SET1WI)和自旋回波T2加权成像(SET2WI);扫描方位以NOP平面为基准扫描。分别测量两组视神经眼球后神经膨大段直径、眶内段视神经直径、长度,管内段视神经直径及该段视神经起始至同侧视交叉的长度,后者与眶内段视神经长度之和即代表颅外段视神经的长度。结果 NOP平面上,正常人眼球后神经膨大段直径为4.2±0.56mm,眶内段直径为3.1±0.45mm、长度为24.6±2.88mm,管内段视神经直径为3.2±0.49mm,至同侧视交叉的长度为18.7±2.40mm,颅外段视神经的长度为43.3±3.83mm。统计分析,正常成人组内性别和年龄、双侧视神经之间无显著差异。 结论 NOP平面评价视神经有很大优势,MRI可以很好显示视神经的形态,是研究其解剖和疾病的有效检查手段。     

Rural-urban differentials of premature mortality burden in south-west China

Background  

Yunnan province is located in south western China and is one of the poorest provinces of the country. This study examines the premature mortality burden from common causes of deaths among an urban region, suburban region and rural region of Kunming, the capital of Yunnan.     

云南不同产地灯盏细辛药材中灯盏乙素的HPLC测定

目的：以灯盏乙素的含量为指标来比较云南不同产地灯盏细辛药材的质量差异。方法：灯盏细辛药材经50％乙醇提取，用高效液相色谱方法（C18柱，用甲醇-乙腈-0．5％甲酸为流动相梯度洗脱）测定灯盏乙素的含量。结果：云南不同产地灯盏细辛中灯盏乙素的含量在0．72％～2．95％之间，平均含量1．40％．结论：云南不同产地灯盏细辛药材质量基本一致，以弥勒县等传统产区的药材灯盏乙素含量相对较高。     

Poststroke DNA immunization against neurite growth inhibitors is beneficial to the recovery from local cerebral ischemia in rats

BACKGROUND： Inhibitory signals, i.e. neurite growth inhibitors （NGIs）, presenting on central nervous system （CNS） myelin have been shown to play a crucial role in inhibiting lesioned axonal sprouting and leading to less functional recovery. Vaccines targeting NGIs may provide multifactorial protection against brain insults by overcoming the inhibitory effects of these NGIs and boosting the body＇s immune repair mechanisms. OBJECTIVE： To evaluate the effect of poststroke DNA immunization against NGIs on the rehabilitation for sensorimotor function of rat models of local cerebral ischemia. DESIGN： Completely randomized grouping design, and controlled experiment. SETTING： Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute, Singapore. MATERIALS： Sixty adult male Sprague-Dawley rats ranging in age from 45 to 120 days and in weight from 180 to 250 grams were provided by Animal Center of Department of Anatomy, Faculty of Medicine, National University of Singapore. pcDNA3.1（＋）-neurite growth inhibitors （pcDNA-NGIs） a gift was provided by Dr. Xiao from Department of Clinical Research, Singapore General Hospital, Singapore. METHODS： The experiment was carried out at Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute, Singapore from August 2003 to April 2005. （1）The involved rats were randomized into 3 groups： pcDNA-NGIs group （group A）, pcDNA3.1 （＋） group （group B） and model group （group C）, with 20 rats in each group. Left focal cerebral ischemia （FCI） was permanently induced through middle cerebral artery occlusion （MCAO） with the assistance of an operating microscope. Successful MCAO was determined by a 20% decrease to baseline in the ipsilateral cerebral blood flow. 100 μg of pcDNA-NGIs eluted in phosphate-buffered saline （PBS） was intramuscularly injected into the tibial muscle once a week after MCAO for 6 weeks in group A. As control, pcDNA3.1 （＋） was also administrated in the same way in group B and nothing was administrated in group C. （2） The modified neurological severity score （mNSS）, a composite of motor, sensory, reflex and balance tests, was used to test the sensorimotor deficit. The mNSS was graded on a scale of 0 - 18, i.e. normal score was 0, maximal deficit score was 18, and 1 point was warded for the inability to perform the tasks or the lack of a tested reflex. （3） The newly generated axons of corticorubral projection were traced by stereotaxic guided injection of 100 g/L biotinylated dextran amine. Rats were sacrificed two weeks after tracing, and cryostat coronal sections of midbrains （30μm） were reacted to BDA according to the manufacturer＇s instruction by the free-floating method. Images were captured on a DM RXA2 LEICA Microscope with a Spot Digital Camera system （Germany）, and the numbers of labeled axons on the denervated side in four standard coronal sections including the red nucleus were manually quantified. MAIN OUTCOME MEASURES： （1） The number of newly generated axons of corticorubral projection. （2）The improvement in sensorimotor deficit. RESULTS： All the involved 60 rats entered the stage of final analysis. （1） The number of newly generated axons of corticorubral projection of rats： Only ipsilateral axons of CRP were noted with little evidence of fibers crossing to the contralateral red nucleus in rats of groups B and C. More BDA-positive fibers crossing the midline and terminating in the contralateral red nucleus in appropriate target areas mirroring the non-differentiated red nucleus were found in rats of group A. Quantitative analysis showed that BDA-labeled axons in the denervated side of rats in group A were more than those in group B （P 〈 0.05）. （2） Improvement in sensorimotor deficit of rats： At 2 weeks after immunization, significant improvement in sensorimotor deficit was found in rats of group A. There were significant differences of improvement in sensorimotor deficit of rats between group A and group B or group C at 12 and 14 weeks after immunization （P 〈 0.05）. CONCLUSION： （1） Poststroke DNA immunization against NGIs leads to increased sensorimotor recovery following FCI and compensatory newly growth of axons from corticorubral projection.     

云南省卫生资源配置标准的弹性系数研究

目的　在进行云南省区域分类基础上制定云南省区域卫生资源配置标准标志值后 ,根据云南省各个地区的特点增加不同弹性系数。方法　采用流行病学研究方法 ,收集和分析云南省不同地州市 1990～ 1999年有关人口、社会经济状况及卫生经费的投入、居民健康状况、居民文化、生活水平、少数民族状况、旅游地区、边境线长短及贫困状况等资料。结果　研究结果表明曲靖地区、玉溪市、保山地区增加弹性系数最少 ,分别为 0 67%、 1 5 8%和1 68% ,怒江州、迪庆州和西双版纳州增加弹性系数最多 ,分别为 11 15 %、 10 2 5 %和 9 84 %。其它地区的弹性系数分别为昆明市 5 88% ,昭通地区 2 3 1% ,楚雄州 2 3 0 % ,红河州 7 0 3 % ,文山州 5 5 3 % ,思茅地区 7 4 3 % ,大理州4 94 % ,德宏州 6 78% ,丽江地区 4 3 5 % ,临沧地区 6 13 %。结论　云南省区域卫生配置标准的弹性系数研究为云南省卫生资源区域分类配置标准提供了科学依据 ,不同弹性系数体现了云南省不同地区的卫生资源区域分类配置标准的公平性、合理性及实用性