Selectivity of repaglinide and glibenclamide for the pancreatic over the cardiovascular KATP channels

Aims/hypothesis Sulfonylureas and glinides close beta cell ATP-sensitive K⁺ (K_ATP) channels to increase insulin release; the concomitant closure of cardiovascular K_ATP channels, however, leads to complications in patients with cardiac ischaemia. The insulinotrope repaglinide is successful in therapy, but has been reported to inhibit the recombinant K_ATP channels of beta cells, cardiocytes and non-vascular smooth muscle cells with similar potencies, suggesting that the (patho-)physiological role of the cardiovascular K_ATP channels may be overstated. We therefore re-examined repaglinide’s potency at and affinity for the recombinant pancreatic, myocardial and vascular K_ATP channels in comparison with glibenclamide.Methods K_ATP channel subunits (i.e. inwardly rectifying K⁺ channels [Kir6.x] and sulfonylurea receptors [SURx]) were expressed in intact human embryonic kidney cells and assayed in whole-cell patch-clamp and [³H]glibenclamide binding experiments at 37°C.Results Repaglinide and glibenclamide, respectively, were ≥30 and ≥1,000 times more potent in closing the pancreatic than the cardiovascular channels and they did not lead to complete inhibition of the myocardial channel. Binding assays showed that the selectivity of glibenclamide was essentially based on high affinity for the pancreatic SUR, whereas binding of repaglinide to the SUR subtypes was rather non-selective. After coexpression with Kir6.x to form the assembled channels, however, the affinity of the pancreatic channel for repaglinide was increased 130-fold, an effect much larger than with the cardiovascular channels. This selective effect of coexpression depended on the piperidino substituent in repaglinide.Conclusions/interpretation Repaglinide and glibenclamide show higher potency and efficacy in inhibiting the pancreatic than the cardiovascular K_ATP channels, thus supporting their clinical use.The first two authors listed contributed equally to this work.     

Motor inhibition and cognitive flexibility in eating disorder subtypes

Anorexia Nervosa (AN) and Bulimia Nervosa (BN) are complex Eating Disorders (EDs). Even if are considered two different diagnostic categories, they share clinical relevant characteristics. The evaluation of neurocognitive functions, using standardized neuropsychological assessment, could be a interesting approach to better understand differences and similarities between diagnostic categories and clinical subtypes in EDs thus improving our knowledge of the pathophisiology of EDs spectrum. This study explored cognitive flexibility and motor inhibition in patients with AN considering both Restricter and Binge/Purge subtypes, patients with BN and healthy comparisons subjects (HC). Intra-Extra Dimentional Set shifting Test and Stop Signal Task, selected from CANTAB battery, were administered to analyzed set-shifting and motor inhibition respectively. AN patients showed a deficient motor inhibition compared to HC, while no evidence for impaired motor inhibition was found in BN patients; a significant relationship between commission errors in the Stop Signal Task and attentional impulsiveness was found. Moreover, no difference in set-shifting abilities was found comparing all clinician groups and HC. So our results indicated no cognitive impairment in these two cognitive functions in BN patients, while AN and BN showed different performances in motor inhibition. A similar cognitive profile was found in other obsessive compulsive spectrum disorders. Finally, the paper suggests a new interactive approach for the study of cognitive profile in psychiatric disorders; it might be more useful since it is more closely related to the executive functions complexity.     

不同亚型注意缺陷多动障碍儿童家庭环境与行为比较

目的 对注意缺陷多动障碍(ADHD)常见亚型的家庭环境与冲突处理能力进行比较,寻求ADHD行为问题的危险因素,探讨不同亚型认知损伤的差异.方法 选择ADHD注意缺陷型(ADHD-Ⅰ型)和混合型(ADHD-C型)各39例、正常儿童38名,进行Conners父母问卷(PSQ)、家庭环境量表(FES-CV)的评定和空间整合Simon-Stroop任务的完成.结果 1.量表:①PSQ:ADHD-Ⅰ型和ADHD-C型的品行问题[(0.65±0.32)分,(1.05±0.44)分]、学习问题[(1.58±0.58)分,(1.97±0.52)分]、冲动-多动[(1.06±0.46)分,(1.56±0.60)分]及多动指数[(1.01±0.31)分,(1.45±0.40)分]与正常组[(0.42±0.24)分,(0.77±0.49)分,(0.58±0.40)分,(0.55±0.34)分]比较,差异有统计学意义(P＜0.05);两亚型间上述4个评分差异有统计学意义;②FES-CV:ADHD-Ⅰ型和ADHD-C型的亲密度[(6.75±2.27)分,(6.61±2.03)分]、情感表达[(5.03±1.54)分,(5.06±1.91)分]、矛盾性[(3.28±1.70)分,(4.61±2.56)分]、知识性[(3.83±2.30)分,(3.61±1.81)分]、娱乐性[(3.70±2.12)分,(3.47±2.32)分]、控制性[(4.78±2.23)分,(4.81±2.07)分]与正常组[(8.06±1.71)分,(6.03±1.54)分,(2.36±1.44)分,(4.86±1.91)分,(4.83±2.29)分,(3.67±1.90)分]比较,差异有统计学意义(P＜0.05);两亚型间矛盾性评分差异有统计学意义.2.行为学:Simon不一致(Siin)和Stroop不一致(Stin)条件,ADHD-Ⅰ型和ADHD-C型的反应正确率(Siin:0.76±0.13,0.69±0.13;Stin:0.82±0.10,0.78±0.08)和反应时[Siin( 876.4±97.34) ms,( 893.8±130.1) ms;Stin(864.4±91.82) ms,(860.2±125.0) ms]与正常组[Siin(0.81 ±0.11)ms,(810.4±136.1) ms;Stin(0.87±0.08) ms,(797.4±136.1 )ms]比较,差异有统计学意义(P＜0.05);两亚型间Siin及Stin的正确率差异有统计学意义.3.Pearson相关分析:FES-CV某些环境因素与ADHD儿童的行为特点存在不同程度相关性.结论 不良的家庭环境是ADHD儿童发生行为问题的危险因素,且ADHD-C型的家庭、行为问题较ADHD-Ⅰ型突出.ADHD两亚型均存在冲突信息的处理能力不足,损害程度有所不同,ADHD-C型较ADHD-Ⅰ型重.     

Role of Elective Nodal Irradiation in Patients With ypN0 After Neoadjuvant Chemotherapy Followed by Breast-Conserving Surgery (KROG 16-16)

Background

Given the lack of established indications for elective nodal irradiation (ENI) in ypN0 patients after neoadjuvant chemotherapy (NAC) and breast-conserving surgery (BCS), we set out to investigate the role of ENI in ypN0 patients according to subtype and pathologic complete remission (pCR) status.

Clear Cell Type A and B Molecular Subtypes in Metastatic Clear Cell Renal Cell Carcinoma: Tumor Heterogeneity and Aggressiveness

Background

Intratumor molecular heterogeneity has been reported for primary clear cell renal cell carcinoma (ccRCC) tumors; however, heterogeneity in metastatic ccRCC tumors has not been explored.

女性膀胱脱垂亚型患者的二维超声声像图特征分析

目的 分析经会阴二维超声对女性膀胱脱垂亚型的声像图特征,为超声诊断女性膀胱脱垂提供参考.方法 选择2013年7月至2016年6月海南省妇幼保健院收治的88例经盆腔器官脱垂定量评估系统进行检测初步确诊为阴道前壁膨出、膀胱脱垂的患者作为观察组,另选择88例健康体检者作为对照组.对所有入选者膀胱所处位置超声检查,并测定其膀胱尿道后角静息期和张力时期的倾斜角,分析声像图特征.结果 在静息状态以及最大Valsalva动作时,观察组患者的尿道前角为(121.34±28.74)°,对照组为(123.62±13.71)°,差异无统计学意义(P>0.05),但是观察组患者的前角缩小率为(15.60±0.14)%、明显大于对照组的(9.02±0.07)%,差异有统计学意义(P<0.05);在静息状态以及最大Valsalva动作时,观察组患者和对照组的尿道后角分别为(113.25±12.01)°、(113.29±14.37)°,后角缩小率分别为(3.75±0.16)%、(3.81±0.26)%,差异均无统计学意义(P>0.05);静息状态下,观察组患者和对照组的的会阴长度分别为(5.40±2.03)cm、(5.39±2.51)cm,厚度分别为(7.11±1.36)mm和(6.82±1.29)mm,差异均有统计学意义(P>0.05);观察组患者中直肠膨出2例,膨出物深度为(16.15±5.24)mm,会阴运动过度10例,膨出物深度为(10.15±1.17)mm.结论 经会阴二维超声技术可以获得膀胱脱垂亚型的超声特征,为临床诊断提供参考.     

H5N6人禽流感病毒分离株序列分析及其生物学特性研究

目的 分析研究H5N6人禽流感病毒基因组序列特征,明确该病毒的分子进化及生物学特性.方法 从GenBank和GISAI中获取人H5N6分离株全序列,通过软件BioEdit7.0.9对各节段基因与其他相关毒株序列进行比对.用软件Mega 5.0,Neighbor-Joining法绘制血凝素(HA)和神经氨酸酶(NA)基因进化树,并全面分析病毒株的基因组序列特征、病毒进化及来源、传染性、致病性和药物敏感等.结果 H5N6病毒的基因组完全属于禽源特征,根据病毒进化及来源可分为两大类.HA基因都属于H5亚型的2.3.4.4进化支,NA基因都来源于H6N6亚型毒株,属于欧亚谱系.其余6段内部基因分别来自于H9N2亚型或H5亚型2.3.2.1进化支毒株.该病毒尚不能在人与人之间有效传播,呈现高致病性病毒特征,对奥斯他韦敏感,但部分毒株对金刚烷胺类药物耐药.结论 H5N6人禽流感分离株并不属于同一毒株,是由H5N1、H5N2、H6N6、H9N2等亚型毒株通过不同组合而重配产生,需加强对这类病毒及其宿主的监控.     

Incidence of epithelial ovarian cancer according to histologic subtypes in Korea, 1999 to 2012

Objective

To investigate trends in the incidence of epithelial ovarian cancer (EOC), according to histologic subtypes, in Korean women between 1999 and 2012.

Methods

Data from the Korea Central Cancer Registry recorded between 1999 and 2012 were evaluated. The incidences of EOC histologic subtypes were counted. Age-standardized incidence rates (ASRs) and annual percentage changes (APCs) in incidence rates were calculated. Patient data were divided into three groups based on age (<40, 40 to 59, and >59 years), and age-specific incidence rates were compared.

Results

Overall, the incidence of EOC has increased. Annual EOC cases increased from 922 in 1999 to 1,775 in 2012. In 1999, the ASR was 3.52 per 100,000 and increased to 4.79 per 100,000 in 2012 (APC, 2.53%; p<0.001). The ASRs in 2012 and APCs between 1999 and 2012 for the four major histologic subtypes were as follows (in order of incidence): serous carcinoma (ASR, 2.32 per 100,000; APC, 4.34%; p<0.001), mucinous carcinoma (ASR, 0.73 per 100,000; APC, –1.05%; p=0.131), endometrioid carcinoma (ASR, 0.51 per 100,000; APC, 1.48%; p=0.032), and clear cell carcinoma (ASR, 0.50 per 100,000; APC, 8.13%; p<0.001). In the sub-analyses based on age, clear cell carcinoma was confirmed as the histologic subtype whose incidence had increased the most since 1999.

Conclusion

The incidence of EOC is increasing in Korea. Among the histologic subtypes, the incidence of clear cell carcinoma has increased markedly across all age groups since 1999.     

北京市吸毒人群HCV感染状况及基因特征分析

目的 分析北京市吸毒人群HCV感染情况及其HCV的病毒基因特征.方法 利用ELISA方法和Real-time PCR方法同时检测684名吸毒人群血清中HCV抗体和HCV RNA,确定该人群的HCV感染情况.对HCV抗体或RNA检测阳性的样本进行C/E1和NS5B基因区扩增并对扩增产物进行序列测定,分析吸毒人群HCV基因亚型构成.结果 吸毒人群HCV感染率为26.2％(179/684).142例样本的C/E1或NS5B基因区扩增成功,基因进化分析发现8种HCV基因亚型:1a、1b、2a、3a、3b、6a、6n和6u.结论 伴随着人口流动性的增加,目前北京市吸毒人群HCV流行情况复杂,具有多种基因亚型.