Intraplaque neovascularization as a novel therapeutic target in advanced atherosclerosis

Introduction: Atherosclerosis is a lipid-driven inflammatory process with a tremendously high mortality due to acute cardiac events. There is an emerging need for new therapies to stabilize atherosclerotic lesions. Growing evidence suggests that intraplaque (IP) neovascularisation and IP hemorrhages are important contributors to plaque instability.

Areas covered: Neovascularization is a complex process that involves different growth factors and inflammatory mediators of which their individual significance in atherosclerosis remains poorly understood. This review discusses different aspects of IP neovascularization in atherosclerosis including the potential treatment opportunities to stabilize advanced plaques. Furthermore, we highlight the development of accurate and feasible in vivo imaging modalities for IP neovascularization to prevent acute events.

Expert opinion: Although lack of a valuable animal model of IP neovascularization impeded the investigation of a causal and straightforward link between neovascularization and atherosclerosis, recent evidence shows that vein grafts in ApoE*3 Leiden mice as well as plaques in ApoE^?/- Fbn1^C1039G+/- mice are useful models for intraplaque neovessel research. Even though interference with vascular endothelial growth factor (VEGF) signalling has been widely investigated, new therapeutic opportunities have emerged. Cell metabolism, in particular glycolysis and fatty acid oxidation, appears to perform a crucial role in the development of IP neovessels and thereby serves as a promising target.     

Orbital colour Doppler imaging in carotid-cavernous sinus fistula

Background: Colour Doppler imaging (CDI) is a recent advance in ultrasonography that allows for colour-encoded blood flow data of a vascular structure to be displayed simultaneously on a conventional real-time gray-scale B mode image. Real time A and B mode ultrasonography have been used for diagnostic evaluation of ophthalmic disorders since the early 1960s. The haemodynamic characteristics of the ophthalmic circulation have recently been studied by the use of CDI.
Method: We present three cases of carotid-cavernous sinus fistulas with different presentations. In each case, orbital CDI was used in evaluating the patient's condition.
Results: Orbital CDI was successful in confirming the diagnosis in all three cases. CDI was capable of showing the haemodynamic changes in the orbital vasculature which resulated from carotid-cavernous sinus fistula.
Conclusion: This non-invasive technique presents as an excellent alternative to invasive vascular studies such as angiography for the diagnosis and evaluation of carotid-cavernous sinus fistulas.     

胀果甘草中皂甙Ⅰ和Ⅱ的结构鉴定

胀果甘草中皂甙Ⅰ和Ⅱ的结构鉴定邹坤，赵玉英，张如意（北京医科大学植化教研室北京１０００８３）继前文工作（１，２，３），我们利用大孔吸附树脂初步分离，ＨＰＬＣ进一步分离，从胀果甘草（Ｇｌｙｃｙ－ｒｒｈｉｚａｉｎｆｌａｔａＢａｔ）根及根茎的１０％乙醇提取...     

Disulfide linkage to polyacrylic resin for automated Fmoc peptide synthesis. Immunochemical applications of peptide resins and mercaptoamide peptides

The use of disulfide bonds for peptide–resin linkage in solid-phase peptide synthesis was investigated using polyacrylic polymers (Expansin^TM) and automated Fmoc methodology. The disulfide moiety was bound to the support either by coupling a protected bifunctional handle or by an original stepwise procedure. Among the three different disulfide handles that were investigated, only the aminoethyldithio-2-isobutyric acid (AEDI) handle was stable enough to achieve peptide synthesis. A series of peptides of up to 10–20 amino acids were prepared in this manner, in good yield and purity. Rapid and quantitative peptide release was obtained by reduction with equimolecular amounts of dithiothreitol at pH 9 or tris(2-carboxymethyl) phosphine at pH 4.5. This allowed direct and rapid coupling of the released cysteamide peptides to an activated protein carrier and the use of free or resin-bound forms of the antigen in immunoassays.     

丙酰螺旋霉素I的分离与鉴别

用大孔吸附树脂等方法分离丙酰螺旋霉素（ＰｒｏＳＰＭ），除得到以前分离的丙酰螺旋霉素ＩＩＩ（ＰｒｏＳＰＭＩＩ）外，又得到一个新成分。根据其理化性质和波谱［ＵＶ，ＨＲＭＳ，１ＨＮＭＲ，１３ＣＮＭＲ（含ＤＥＰＴ）和１Ｈ１３ＣＣＯＳＹ］数据，并与ＰｒｏＳＰＭＩＩ比较，ＰｒｏＳＰＭＩＩ仅Ｃ３酰基不同，命名为丙酰螺旋霉素ＩＩ（ＰｒｏＳＰＭＩＩ）。     

Central venous catheter tip malposition

Central venous catheters are commonly utilised to gain vascular access for varied clinical indications. Successful central venous catheter placement requires not only technical expertise, but also awareness of the potential complications. This article reviews the major procedural and post-procedural complications resulting from central venous catheter tip malposition.     

胚胎干细胞应用及其伦理学问题

目的:介绍胚胎干细胞的研究成果及其可能的临床应用,同时对胚胎干细胞应用中的伦理学问题进行探讨。资料来源:应用计算机检索Medline1996-01/2006-12与胚胎干细胞相关的文章,检索词为“embryonicstemcells,application,morality”,限定文献语种为“English”;同时检索万方数据库2000-01/2006-12相关文章,检索词为“胚胎干细胞,应用,伦理”,限定文献语种为中文。资料选择:共检索到相关文献290条,进一步查找全文,选择与胚胎干细胞可能的应用、以及与其应用相关的论理学讨论相关的文章,筛除明显重复文献,最后纳入30条文献进行综述。资料提炼:30条文献中论述胚胎干细胞可能的应用文章有18篇,探讨胚胎干细胞应用中的伦理学问题的12篇。资料综合:①目前认为,胚胎干细胞在人类医学方面可能应用于癌症、心血管疾病、神经系统疾病、糖尿病、肝脏疾病、烧伤和创伤、骨和软骨疾病等的治疗,胚胎干细胞还能用于器官组织移植、基因治疗和基因功能分析以及新药研制和开发等领域。②国内已经规定用于研究的人胚胎干细胞只能通过4种方式获得:体外受精时多余的配子或囊胚(14d内的胚胎);自然或自愿选择流产的胎儿细胞;体细胞核移植技术所获得的囊胚和单性分裂囊胚;自愿捐献的生殖细胞。同时禁止进行生殖性克隆人的任何研究。结论:胚胎干细胞对临床疾病治疗的应用价值不可估量,在积极鼓励开展胚胎干细胞研究的同时,应加强管理,制定出相应的管理法规和制度,促进胚胎干细胞研究向健康和正确的方向发展。     

Improved efficacy and tolerability of retinoic acid in acne vulgaris: a new topical formulation with cyclodextrin complex ψ

OBJECTIVES: Retinoic acid (RA) has long been used, both topically and systemically, for disorders of keratinization, acne and related disorders. In the present study, the efficacy and tolerability of topical RA prepared as a cyclodextrin beta complex (beta-CD) is investigated in 66 acne vulgaris patients. METHODS: This randomized, double-blind, placebo-controlled study compares nightly topical application of RA/beta-CD complex hydrogel formulation (0.025%), RA/beta-CD complex in moisturizing base (0.025%), hydrogel base, moisturizer base or a commercial RA gel (0.05%) in acne vulgaris patients. Improvement of acne was assessed using a 5-point improvement scale and by measuring sebum and moisture content of the skin using an SM 810 sebumeter/corneometer. RESULTS: After 3 months of treatment, mean scores of acne improvement on the 5-point scale were 4 with the RA/beta-CD complex hydrogel formulation, 4.1 with the RA/beta-CD complex in moisturizing base, 1.2 with hydrogel placebo base, 1.1 with moisturizer placebo base and 3 with the commercial RA product. All patients treated with the commercial product experienced local side-effects. One patient discontinued due to severe irritation. None of the patients treated with the RA/beta-CD complex in the moisturizing base and hydrogel formulation experienced significant local irritation, although the sebum content of the skin decreased after application of the RA/beta-CD preparations. This change was not significant compared to controls. The moisture content of the skin was better preserved in the group treated with the RA/beta-CD complex in the moisturizing base. CONCLUSION: The topical RA/beta-CD complex, in hydrogel and moisturizing base, was more effective than the twice concentrated commercial RA product. There were few topical side-effects with this new formulation, which increases patient compliance. Topical RA/beta-CD (0.025% RA) did not significantly reduce sebum secretion but may help to preserve optimum epidermal moisture content with the proper base formulation. This is the first study in the literature reporting efficacy and tolerability of the topical RA/beta-CD complex in acne vulgaris. We conclude that the topical RA/beta-CD complex displays an improved efficacy and tolerability profile and is an effective treatment alternative for acne vulgaris.