Recycling and EH domain proteins at the synapse

In neurons, a network of endocytic proteins accomplishes highly regulated processes such as synaptic vesicle cycling and the timely internalization of intracellular signaling molecules. In this review, we discuss recent advances on molecular networks created through interactions between proteins bearing the Eps15 homology (EH) domain and partner proteins containing the Asn–Pro–Phe (NPF) motif, which participate in important aspects of neuronal function as the synaptic vesicle cycle, the internalization of nerve growth factor (NGF), the determination of neuronal cell fate, the development of synapses and the trafficking of postsynaptic receptors. We discuss novel functional findings on the role of intersectin and synaptojanin and then we focus on the features of an emerging family of EH domain proteins termed EHDs (EH domain proteins), which are important for endocytic recycling of membrane proteins.     

从“治未病”思想探讨中医药防治EH相关子宫内膜癌的研究意义

子宫内膜癌为女性生殖道三大恶性肿瘤之一。子宫内膜增生症(endometrial hyperplasia,EH)乃子宫内膜癌的癌前病变,因而早期诊断和治疗EH非常必要。中医药防治EH相关子宫内膜癌有其应用简便、价格低廉、有效安全等优势,符合中医"治未病"的思想。由此推理,中医药防治EH相关子宫内膜癌有着广阔前景,值得深入研究。     

A psoriasis vulgaris protective gene maps close to the HLA-C locus on the EH18.2-extended haplotype

We determined the molecular haplotypes of the HLA-A, HLA-C and HLA-B loci and the MHC class I-B-related (MIB) microsatellite in 179 unrelated psoriatic patients (72 familial cases) and in 120 controls. The HLA-A*3002-Cw*0501-B*1801-MIB1 haplotype showed a strong negative association with psoriasis vulgaris (PV) and in particular with familial PV, revealing the presence of a PV-protective gene. Analysis of association and linkage disequilibrium of the single alleles and the various two-three-four-locus segments of this haplotype indicated the presence of a protective gene telomeric to the HLA-C locus. This finding was confirmed in 13 informative multiplex PV families, in which at least one parent carried the EH18.2 haplotype. In two families, an affected sibling presented HLA-A/C recombination on the EH18.2 haplotype. A study of 12 polymorphic microsatellites in all members of the informative families, 145 PV patients, 120 controls and 32 EH18.2 homozygous healthy individuals demonstrated that the protection conferred by the EH18.2 haplotype lies within a 170 kb interval between the C143 and C244 loci, most probably in a 60 kb segment between the C132 and C244 loci.     

原发性高血压患者骨量减少机制初探

为探讨原发性高血压 (EH)与骨量减少的关系 ,采用双能X线骨密度仪测定了 1 2 1例肝、肾功能正常的EH患者的腰椎 (L2 ～L4 )、股骨上端的骨密度 (BMD) ;采用放免法测定血清骨钙素 (BGP)、甲状旁腺素中间片段 (PTH m) ;采用酶免法测定尿脱氧吡啶啉 (DPD)。结果 :EH病人骨密度均低于正常对照组 ,除女性≤ 4 0岁组外P均 <0 .0 1 ;血清BGP、PTH m、DPD均高于正常对照组 (P <0 .0 1 ) ;且BGP、PTH m、DPD与骨密度呈负相关 ,r分别为 -0 .30 7、-0 .2 68、-0 .2 51 (P <0 .0 1 ) ;而血清钙、磷、碱性磷酸酶与正常对照组无显著差异 (P >0 .0 5) ;男女EH病人骨量减少检出率分别为 4 4.83%及 36.50 % ,骨质疏松检出率分别为 6.90 %及 2 6.98% ,且以股骨上端华氏三角区骨量减少为著。结论 :EH病人存在钙、磷代谢紊乱 ,可导致骨量减少 ,以骨吸收大于骨形成、高骨转换为特点。提示在治疗高血压的同时应补充活性维生素D及钙剂 ,防治骨质疏松的发生。     

缬沙坦降血压和逆转左心室肥厚的作用观察

目的 观察缬沙坦降压疗效及对原发性高血压(EH)左心室肥厚(LVH)的逆转作用。方法 入选患者服用缬沙坦80—160mg，晨服一次，治疗12周，用携带式动态血压监测仪监测血压，用超声心动图测定患者的左心室结构及功能改变。结果 缬沙坦使24小时血压稳定下降，室间隔厚度、左心室后壁厚度、左心室舒张末内径、左室心肌重量指数均较治疗前显著改善(P＜0．01)。结论 缬沙坦能有效治疗高血压，有逆转左心室肥厚，改善左心室舒张功能。     

Temporal changes in extra-axial brain hematoma's signal intensity in magnetic resonance images of trauma patients: A preliminary,technical study

IntroductionDating the exact or estimated time of trauma is an important issue facing forensic medicine. Several clinical and radiological methods were used to achieve this purpose. In the recent study, we aimed to track the changes in the signal intensity of the extra-axial brain hematoma using magnetic resonance imaging (MRI) conventional sequences as well as diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC).Materials and methodsConsidering inclusion and exclusion criteria, all patients with blunt head trauma were involved. After proper management., stabilization, and resuscitation, the participants were assessed using conventional sequences of MRI and DWI twenty-four hours, forty-eight hours, and three weeks after the injury. Temporal changes of signal intensity were compared by Wilcoxon ranged test.ResultsSixteen patients sustaining blunt head trauma were included in this study. The study showed that during the time, diffusion restriction could be seen in an extraaxial hematoma. At the first 24 hours, the signal of hematoma was void in 87.5% of DWI and 100% of ADC. On the second day, they were hypo-signal in 75% of DWI and 100% 0f ADCs, and after three weeks, 100% of cases were hyper-signal in DWI and hypo-signal ADCs.ConclusionThis preliminary study has shown that the DWI can be used to detect and track the extra-axial hematoma. The signal intensity was void during the first twentyfour hours, although it became hypo-signal after 48 hours. Of note, the diffusion restriction is noted after three weeks.     

Different actions of ecdysis-triggering hormone on the brain and ventral nerve cord of the hornworm, Manduca sexta

Ecdysis, or the shedding of the old cuticle, depends on coordinated stereotyped behaviors, regulated by a number of neuropeptides. In the hornworm, Manduca sexta, two neuropeptides interact, namely ecdysis-triggering hormone (ETH) and eclosion hormone. We looked at the effects of ETH in vivo and in vitro, on the brain and the ventral nerve cord to determine the roles played by these hormones. We monitored ecdysis onset and the presence of cGMP and eclosion hormone immunoreactivity. In vivo, only a fraction of larvae lacking the cell bodies containing eclosion hormone, and injected with ETH, were able to undergo ecdysis, with a delayed response. These animals showed strongest cGMP immunoreactivity in the subesophageal and thoracic ganglia, with concomitant reductions in eclosion hormone immunoreactivity in descending axons in comparison with animals not undergoing ecdysis. Animals lacking the brain showed reduced to no cGMP levels in all ganglia. In vitro, isolated CNS preparations lacking the brain initiated ecdysis motor programs after incubation in ETH, with faster onset times than controls, and with reduced cGMP immunoreactivity. If ETH was applied only to the brain of the isolated CNS, cGMP immunoreactivity was noted primarily in the subesophageal and thoracic ganglia, with a decrease in eclosion hormone immunoreactivity in descending axons. ETH addition to the rest of the nerve cord showed reduced eclosion hormone immunoreactivity but little to no cGMP immunoreactivity in any ganglion. Controls showed strong cGMP immunoreactivity in all ganglia, and even greater reductions in eclosion hormone staining after ETH application. These results support previous suggestions that eclosion hormone is required for a positive feedback loop with ETH as well as onset of an inhibitory component, but also suggest that ETH stimulates eclosion hormone release at multiple spike initiation zones. The resultant up regulation of cGMP does not appear to be required for onset of ecdysis. A new model for ecdysis regulation is considered.     

缓释异搏定和开搏通对高血压病纤溶活性的影响

采用发色底物法测定了50例Ⅰ、Ⅱ期高血压病(EH)患者组织型纤溶酶原激活剂(t-PA)及其抑制物(PAI-1)活性,并与25例正常人对照.其中21例EH患者接受缓释异搏定治疗,19例EH患者接受开搏通治疗,共12周.结果显示:EH患者t-PA活性下降(P<0.05),PAI-1活性升高(P<0.05).缓释异搏定和开搏通有效降压12周后,t-PA活性升高,PAI-1活性降低.提示EH患者纤溶活性下降,缓释异搏定和开搏通在有效降压的同时能改善高血压患者的纤溶活性.     

不同制备条件对EH复合型骨水泥抗弯强度的影响

目的 探讨不同制备条件对EH 复合型骨水泥抗弯强度的影响.方法 分别选择EH 复合型骨水泥的不同粉/液比、不锈钢模具内充填后使用/未使用冲压器固定、试样加热/不加热3 种不同条件制备试样,随后进行抗弯强度测试.结果 不同的粉/液比中,6/4 和10/7 两组间的抗弯强度差异无统计学意义(P=0.05),其余组别之间有显著差异(P<0.05);使用/未使用冲压器试样(粉/液比:10/7)两组抗弯强度值之间有显著性差异(P<0.05);使用/未使用热处理试样(粉/液比10/7, 使用冲压器)抗弯强度, 两组数据间没有显著性差异(P>0.05).结论 当粉/液比为10/7、且使用冲压器固定条件下制备的EH 复合型骨水泥试样,其抗弯强度可达到最大;对试样进行热处理,抗弯强度的变化不显著.     

Structural refinement of inhibitors of urea-based soluble epoxide hydrolases

The soluble epoxide hydrolase (sEH) is involved in the metabolism of arachidonic, linoleic, and other fatty acid epoxides, endogenous chemical mediators that play an important role in blood pressure regulation and inflammation. 1,3-Disubstituted ureas, carbamates, and amides are new potent and stable inhibitors of sEH. However, the poor solubility of the lead compounds limits their use. Inhibitor structure-activity relationships were investigated to better define the structural requirements for inhibition and to identify points in the molecular topography that could accept polar groups without diminishing inhibition potency. Results indicate that lipophilicity is an important factor controlling inhibitor potency. Polar groups could be incorporated into one of the alkyl groups without loss of activity if they were placed at a sufficient distance from the urea function. The resulting compounds had a 2-fold higher water solubility. These findings will facilitate the rational design and optimization of sEH inhibitors with better physical properties.