缺血性脑卒中的A-S-C-O(表型)分类

背景和目的:国际5国脑血管病专家提出一种新的腩卒中亚型分类法,旨在介绍完整的"脑卒中表型"分类的新观念,该分类是包括脑卒中的病因和存在的所有病因相关的疾病,并将病因疾病按严重程度分成3级.     

血管成形术和支架辅助血管成形术治疗颅内动脉粥样硬化的报告标准（下）

本刊经Philip M．Meyers博士代表写作组授权,将“ Reporting standards for angioplasty and stent-assisted angioplasty for intracranial atherosclerosis”译为中文在本刊刊登。标准中对患者的选择、颅内动脉狭窄程度的判断、最佳内科治疗、围手术期处理、血管内治疗、术后并发症等,进行了规范化总结,拟为今后的临床试验和研究的规范化确定标准,以保证结果的可比性,对神经介入医师具有重要的指导意义。     

血管成形术和支架辅助血管成形术治疗颅内动脉粥样硬化的报告标准（上）

背景和目的颅内动脉粥样硬化可造成众多患者发生缺血性卒中。过去10年间血管内治疗技术已经取得突破性进展,能够开展颅内动脉粥样硬化性狭窄的血管内治疗。采用血管成形术和支架辅助阻管成形术治疗颅内动脉粥样硬化性狭窄的患者例数不断增加。但是鉴于目前血管成形术和支架辅助血管成形术治疗狭窄性和闭塞性颅内动脉粥样硬化仍缺乏普遍认可的临床和放射学评估以及皿管内治疗技术及预后的规范,此文就是提供该方面报告标准、术语和书面定义的共识性建议。报告摘要报告标准是在技术评价委员会、神经介入外科学会、介入放射学会、美国神经外科医师协会和神经外科医师代表大会的脑血管外科分会、美国神经科学会的卒中和介入神经病学分会的联合写作组共同起草完成。对1997年1月-2007年12月间,美国国立图书馆医学文献数据库（PubMed）进行计算机检索,旨在确定已发表的狭窄性颅内动脉粥样硬化的神经介入治疗中,能用作质量评价基准的资料。我们尽可能地确定影响神经介入治疗成功及并发症可能性的危险调节变量。对狭窄性和闭塞性颅内动脉粥样硬化进行麻管内治疗的临床试验设计中,不同临床和技术问题可能影响血管内治疗的疗效,此文章为这些问题提供相关的理论基础。该指南中包括对血管内治疗试验报告标准的建议。虽然制定规范和标准主要是出于研究用途,但是这也将有助于临床实践,还适用于所有相关的出版物。结论总之,报告标准提出的建议将有助于构建有效的研究数据库,同时促进产生科学可靠的研究结果,使相似研究之间或内部能够进行可靠的比较。存某些情况下,为报告和出版的一致性,本文中的定义可能是写作组专家的共识性建议。这些建议将促使不同研究组的结果具有直接可比性。     

Intranasal c-di-GMP-adjuvanted plant-derived H5 influenza vaccine induces multifunctional Th1 CD4+ cells and strong mucosal and systemic antibody responses in mice

Vaccination is the best available measure of limiting the impact of the next influenza pandemic. Ideally, a candidate pandemic influenza vaccine should be easy to administer and should elicit strong mucosal and systemic immune responses. Production of influenza subunit antigen in transient plant expression systems is an alternative to overcome the bottleneck in vaccine supply during influenza pandemic. Furthermore, a needle-free intranasal influenza vaccine is an attractive approach, which may provide immunity at the portal of virus entry.The present study investigated the detailed humoral and cellular immune responses in mice vaccinated intranasally or intramuscularly with plant-derived influenza H5N1 (A/Anhui/1/05) antigen alone or formulated with bis-(3′,5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) as adjuvant. The use of c-di-GMP as intramuscular adjuvant did not enhance the immune response to plant-derived influenza H5 antigen. However, intranasal c-di-GMP-adjuvanted vaccine induced strong mucosal and systemic humoral immune responses. Additionally, the intranasal vaccine elicited a balanced Th1/Th2 profile and, most importantly, high frequencies of multifunctional Th1 CD4⁺ cells. Our results highlight that c-di-GMP is a promising mucosal adjuvant for pandemic influenza vaccine development.     

Inhibition of nitric oxide-activated guanylyl cyclase by calmodulin antagonists

Background and purpose:

Nitric oxide (NO) controls numerous physiological processes by activation of its receptor, guanylyl cyclase (sGC), leading to the accumulation of 3′-5′ cyclic guanosine monophosphate (cGMP). Ca²⁺-calmodulin (CaM) regulates both NO synthesis by NO synthase and cGMP hydrolysis by phosphodiesterase-1. We report that, unexpectedly, the CaM antagonists, calmidazolium, phenoxybenzamine and trifluoperazine, also inhibited cGMP accumulation in cerebellar cells evoked by an exogenous NO donor, with IC₅₀ values of 11, 80 and 180 µM respectively. Here we sought to elucidate the underlying mechanism(s).

Experimental approach:

We used cerebellar cell suspensions to determine the influence of CaM antagonists on all steps of the NO-cGMP pathway. Homogenized tissue and purified enzyme were used to test effects of calmidazolium on sGC activity.

Key results:

Inhibition of cGMP accumulation in the cells did not depend on changes in intracellular Ca²⁺ concentration. Degradation of cGMP and inactivation of NO were both inhibited by the CaM antagonists, ruling out increased loss of cGMP or NO as explanations. Instead, calmidazolium directly inhibited purified sGC (IC₅₀= 10 µM). The inhibition was not in competition with NO, nor did it arise from displacement of the haem moiety from sGC. Calmidazolium decreased enzyme V_max and K_m, indicating that it acts in an uncompetitive manner.

Conclusions and implications:

The disruption of every stage of NO signal transduction by common CaM antagonists, unrelated to CaM antagonism, cautions against their utility as pharmacological tools. More positively, the compounds exemplify a novel class of sGC inhibitors that, with improved selectivity, may be therapeutically valuable.