Chronic peripheral administration of somatostatin receptor subtype-4 agonist NNC 26-9100 enhances learning and memory in SAMP8 mice

Selective somatostatin receptor subtype agonists have been proposed as a means to mitigate learning and memory loss associated with Alzheimer's disease. The first aim of this study evaluated blood-to-brain transport and regional brain distribution of NNC 26-9100, a selective somatostatin subtype-4 (sst4) receptor agonist. The entry rate of ¹³¹I-NNC 26-9100 was K_i = 0.25 μl/g min, with an ~ 93% association with the parenchymal component. The second goal of this study was to evaluate the effect of chronic NNC 26-9100 administration (i.p.) on learning and memory, brain Aβ_x-42 levels, and protein expression of sst4 receptor and amyloid precursor protein (APP) in the senescence-accelerated mouse p8 (SAMP8) model of Alzheimer's disease. Mice chronically treated with NNC 26-9100 showed improved learning (day 21) and memory (day 28) using the T-maze paradigm (20 and 200 μg). Ex vivo tissue analyses showed a decline in Aβ_x-42 levels at the 20 μg dose, while no alterations were observed in sst4 receptor or APP protein expression compared to vehicle controls. These findings indicate NNC 26-9100 is taken up into key brain regions associated with learning and memory. Furthermore, chronic administration of NNC 26-9100 improved learning and memory and decreased Aβ_x-42 brain levels. These results suggest sst4 receptor agonists may provide a viable therapy in the treatment of Alzheimer's disease and other forms of cognitive impairment.     

Analgesic effects of JCM-16021 on neonatal maternal separation-induced visceral pain in rats

AIM:To investigate the pharmacological effect of JCM-16021,a Chinese herbal formula,and its underlying mechanisms.METHODS:JCM-16021 is composed of seven herbal plant materials.All raw materials of the formula were examined according to the quality control criteria listed in the Chinese Pharmacopeia(2005).In a neonatal maternal separation(NMS)model,male SpragueDawley rats were submitted to daily maternal separation from postnatal day 2 to day 14,or no specific handling(NH).Starting from postnatal day 60,rats...     

完全切除的Ⅰ期，Ⅱ期和ⅢA期非小细胞肺癌术后放疗联合辅助化疗对生存率的影响：国际诺维本辅助治疗组织随机临床试验

研究背景:1998年术后放疗(post operative radiotherapy,PORT)的meta分析表明术后放疗相关死亡率风险增加21%,术后放疗的作用一直是探讨的热点.     

HPLC分离测定格列齐特片及其有关物质

目的：建立新的HPLC法分离测定格列齐特征及其有关物质。方法：色谱条件为：Shim-Pack VP-ODS(5um,150mm*4.6mm i.d.)色谱柱;甲醇－0．02mol/L磷酸（用三乙胺调节PH至3．5）,（70：30）为流动相;检测波长为229nm。结果：在50－300ug;/ml的浓度范围内线性关系良好。r=0.9999(n=6);平均回收率为100．5％,RSD为0．17％（n=6),重复进样RSD为0．12％（n=6),格列齐特及其有关物质得到基线分离。结论：本法简便,快速,准确,适用于格列齐特及其制剂的质量控制。     

Induction Of Endothelin-1 Expression By Glucose: An Effect Of Protein Kinase C Activation

Enhanced actions or levels of endothelin-1 (ET-1), a potent vasoconstrictor, have been associated with decreased blood flow in the retina and peripheral nerves of diabetic animals and may be related to the development of pathologies in these tissues. Hyperglycemia has been postulated to increase ET-1 secretion in endothelial cells. We have characterized the mechanism by which elevation of glucose is increasing ET-1 mRNA expression in capillary bovine retinal endothelial cells (BREC) and bovine retinal pericytes (BRPC). Elevation of glucose, but not mannitol, from 5.5 to 25 mmol/l for 3 days increased membranous protein kinase C (PKC) activities and ET-1 mRNA in parallel levels by 2-fold in BREC and BRPC. These effects were reversed by decreasing glucose levels to 5.5 mmol/l for an additional 2 days. Glucose-induced ET-1 overexpression was inhibited by a general PKC inhibitor, GF109203X, and a mitogen-activated protein kinase kinase inhibitor, PD98059, but not by wortmannin, a phosphatidylinositol 3-kinase inhibitor. By immunoblot analysis, PKC-beta 2 and -delta isoforms in BREC were significantly increased relative to other isoforms in the membranous fractions when glucose level was increased. Overexpression of PKC-beta 1 and -delta isoforms but not PKC-zeta isoform by adenovirus vectors containing the respective cDNA enhanced in parallel PKC activities, proteins, and basal and glucose-induced ET-1 mRNA expression by at least 2-fold. These results showed that enhanced ET-1 expression induced by hyperglycemia in diabetes is partly due to activation of PKC-beta and -delta isoforms, suggesting that inhibition of these PKC isoforms may prevent early changes in diabetic retinopathy and neuropathy.     

Expression of cadherins and CD44 isoforms in ovarian endometrial cysts

We evaluated the immunohistochemical expression of cadherins and CD44 variants in 20 endometriomas, 20 cystadenomas, 20 borderline ovarian tumours as well as 20 ovarian carcinomas, and the serological and cystic fluid concentrations of soluble E-cadherin and soluble CD44 standard (sCD44sdt) in 20 endometriomas, 20 cystadenomas, six borderline and 11 carcinomas of the ovary. In endometriomas, immunostaining of E- and N-cadherin was negative (20 and 30% respectively). CD44 H, v3 and v6 immunostaining were detected in 63, 10 and 40% respectively. A difference in immunostaining for E-cadherin was found between endometriomas and cystadenomas (P < 0.001) and for N- cadherin between endometriomas and carcinomas (P < 0.001). A difference in CD44H immunostaining was observed between endometriomas and cystadenomas (P < 0.035) but not with borderline ovarian tumours and carcinomas. No difference in serum concentrations of soluble E- cadherins and CD44 standard was found between the four groups of tumours. Cystic fluid concentrations of E-cadherin were lower in endometriomas than in borderline tumours and ovarian carcinomas (P < 0.001). High concentrations of soluble CD44 standard cystic fluid were found in endometriomas than in other ovarian cysts. Endometriomas and borderline tumours share alterations of cadherins and CD44 isoforms which may help in the understanding of the aggressive and invasive potentials of endometriotic cells.      

应用四唑盐比色法对5种骨水泥的细胞毒性的测试

0　引言　应用细胞培养法对牙科材料的生物相容性进行评价是一种简便、有效、经济的方法 .近年来 ,国内外有许多学者报道用 MTT检测细胞活性 ,并认为用 MTT法可以代替活细胞计数、同位素标记进行细胞毒性试验 .我们应用 MTT法对 5种骨水泥的细胞毒性进行了评价 ,并对有关问题进行了讨论 .1　材料和方法1.1　测试材料　 1号 :生物水泥 ,2号 :羟基磷灰石人工骨 ,3号 :氰基丙烯酸酯骨水泥 1号 (自制 ) ,4号 :氰基丙烯酸酯骨水泥 2号 (自制 ) ,5号 :氰基丙烯酸酯骨水泥 3号 (自制 ) .阴性对照采用珊瑚 ,阳性对照采用聚氯乙烯 .1.2　实验步骤…     

冠心病合并2型糖尿病患者血脂检测

目的:观察冠心病(CHD)合并2型糖尿病患者血脂水平的变化,并探讨CHD合并2型糖尿病的危险性与脂质代谢紊乱间的相关性.方法:检测CHD组患者29(男18,女11)例,年龄40～70(平均55.2)岁;CHD合并2型糖尿病组[CHD伴非胰岛素依赖型糖尿病(NIDDM)]患者22(男12,女10)例,年龄41～70(平均56.5)岁;正常对照组[健康献血员31(男17,女14)例,年龄38～50(平均43.5)岁]的血脂水平.结果:CHD伴NIDDM组患者总胆固醇(TC),三酰甘油(TG),低密度脂蛋白胆固醇(LDLC)和载脂蛋白B(ApoB)水平明显高于CHD组患者[TC:(5.87±1.02)mmol/Lvs(4.10±1.13)mmol/L;TG:(2.10±1.05)mmol/Lvs(1.13±0.85)mmol/L;LDLC:(4.23±0.97)mmol/Lvs(2.97±0.90)mmol/L;ApoB:(0.90±0.18)mmol/Lvs(0.58±0.19)mmol/L,均P<0.01],但CHD伴NIDDM组患者高密度脂蛋白胆固醇(HDLC),载脂蛋白A1(ApoA1)水平明显低于CHD组患者[HDLC(0.71±0.12)mmol/Lvs(0.94±0.16)mmol/L,ApoA1:(0.73±0.19)mmol/Lvs(1.03±0.20)mmol/L,均P<0.01].结论:CHD合并2型糖尿病患者在脂质代谢紊乱方面存在更多致CHD的危险因素,应重视这类患者的血脂检测并及时纠正脂质代谢紊乱,以降低CHD的危险性.     

MRI evaluation of the levator ani muscle: anatomic correlations and practical applications

Summary A comparative study of serial anatomic sections in the transverse, frontal and sagittal planes with corresponding MRI sections of the pelvis allowed the authors to define the most suitable sectional planes and MRI modes for a morphologic study of the levator ani muscle. This study shows the value of MRI examination in the assessment of anorectal malformations.

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Les muscles elevateurs de l'anus en IRM. Corrélations anatomiques et applications pratiques

Résumé A partir de l'étude comparative de coupes anatomiques dans les plans transversal, frontal, sagittal et des coupes IRM correspondantes du petit bassin, les auteurs déterminent quels sont les plans de coupe et les modes IRM les plus performants pour l'étude morphologique des muscles élévateurs de l'anus. Cette étude montre l'intérêt de l'examen IRM dans le bilan des malformations ano-rectales opérées.