沉香螺环化合物的研究:10-甲基-螺[4.5]-癸-6-烯-6-羧酸的合成

3-甲基△²环已烯-1-酮(4)与1,4-二溴丁烷在氨钠,液氨中或在叔丁醇钾的苯溶液中进行螺环化反应,得到螺环化合物5a+5b以及双螺环化合物6a+6b。经定量催化氢化;羰基与三甲基硅氰加成反应;硅醚水解;脱水和腈基水解,合成了10-甲基-螺[4.5]-癸-6-烯-6-羧酸(11)。药理试验表明该化合物有一定的麻醉催眠作用。     

复方烧伤喷雾剂的药效学研究

目的：研究以乙酸乙酯为主要溶媒的复方烧伤喷雾的药效学。方法：用烧伤创面感染常见的金黄色葡萄球菌、绿脓假单胞菌、大肠埃希氏菌、普通变形杆菌做豚鼠烧伤感染模型,并用复方烧伤喷雾剂治疗,结果：复方烧伤喷雾剂可促进豚鼠Ⅱ度烧伤创面的愈合,并具有显著的烧伤创面抗感染作用。结论：乙酸乙酯可作为某些中药有效成分的优良提取溶剂。     

纳米靶向给药系统载体材料的研究进展

目的:综述及讨论近年来新材料在靶向给药系统载体材料方面的应用及存在问题。资料来源:以网络数据库资源为主,查询Science Direct,Pubmed,Springer,Ovid等数据库1995-01/2006-06关于靶向给药系统载体材料方面的相关文献,检索词“Targetdrug delivery system”and“Materials”,限定文章的语种种类为“English”;同时检索CNKI数据库2001-01/2006-06的相关文章为补充,限定文章语种种类为中文,检索关键词“靶向给药系统,载体材料”。资料选择:对资料进行初审,纳入标准:①关于靶向给药系统的研究。②应用的较新的材料作为药物载体。排除标准:重复性研究。资料提炼:共收集到122篇文献,98篇符合纳入标准,取其中有关新型载体材料应用于靶向给药系统的30篇相关文献进行归纳总结。资料综合:靶向给药是目前药剂学领域的研究热点之一,但多年来转化为产品的研究成果极为少见。其中关键问题之一就是药物载体材料的研究瓶颈,药剂学研究与材料学研究间学科交叉与衔接的严重滞后阻碍了新型给药系统的产业化。结论:新型给药系统载体材料研究开发尤为重要,载体材料应用的安全性一旦解决,必将带来新型给药系统全面用于临床的新局面,从而使药效得到更好的发挥,提高疾病的预防治疗能力。     

Investigation of the mechanism of action of 2% fusidic acid lotion in the treatment of acne vulgaris

We describe the results of a single-centre, double-blind, vehicle-controlled, parallel group study on the quantitative effects of 2% fusidic acid lotion (Fucidin® lotion) in facial acne vulgaris. The trial was completed by 52 patients aged 15–25 years with mild to moderate acne who had been randomized to either Fucidin® Lotion (n= 25) or its base (n= 27). Primary outcome measures included colony counts of Propionibacterium acnes and microcoecaceae and measurements of skin surface lipid free tatty acids and sebum excretion rate. Clinical assessment was based on the acne grade, count of inflamed and non-inflamed lesions and evidence of a primary irritant dermatitis. There was a variable hut gradual reduction in lesion counts with the maximum improvement at 12 weeks for inflamed lesions, where the reduction was 19·9% for fusidic acid and 247% for the placebo. The non-inflamed lesions decreased by 10·8% in the fusidic acid group and increased by 15·9% in the placebo group; this difference was not statistically significant. Although the fusidic acid reduced the micrococcaceae count by 1 log cycle, inferring adequate compliance, there was no reduction in the counts of P. acnes, surface free fatty acids or sebum excretion rate. This study has failed to explain the mechanism of action of topical fusidic acid.     

Spindles and active vortices in a model of confined filament-motor mixtures

Background

Although biological membranes are organized as lipid bilayers, they contain a substantial fraction of lipids that have a strong tendency to adopt a nonlamellar, most often inverted hexagonal (H_II) phase. The polymorphic phase behavior of such nonbilayer lipids has been studied previously with a variety of methods in the fully hydrated state or at different degrees of dehydration. Here, we present a study of the thermotropic phase behavior of the nonbilayer lipids egg phosphatidylethanolamine (EPE) and monogalactosyldiacylglycerol (MGDG) with a focus on interactions between the lipid molecules in the interfacial and headgroup regions.

Results

Liposomes were investigated in the dry state by Fourier-transform Infrared (FTIR) spectroscopy and Differential Scanning Calorimetry (DSC). Dry EPE showed a gel to liquid-crystalline phase transition below 0°C and a liquid-crystalline to H_II transition at 100°C. MGDG, on the other hand, was in the liquid-crystalline phase down to -30°C and showed a nonbilayer transition at about 85°C. Mixtures (1:1 by mass) with two different phosphatidylcholines (PC) formed bilayers with no evidence for nonbilayer transitions up to 120°C. FTIR spectroscopy revealed complex interactions between the nonbilayer lipids and PC. Strong H-bonding interactions occurred between the sugar headgroup of MGDG and the phosphate, carbonyl and choline groups of PC. Similarly, the ethanolamine moiety of EPE was H-bonded to the carbonyl and choline groups of PC and probably interacted through charge pairing with the phosphate group.

Conclusions

This study provides a comprehensive characterization of dry membranes containing the two most important nonbilayer lipids (PE and MGDG) in living cells. These data will be of particular relevance for the analysis of interactions between membranes and low molecular weight solutes or soluble proteins that are presumably involved in cellular protection during anhydrobiosis.     

Severe Hypertension Following Accidental Clonidine Overdose During the Refilling of an Implanted Intrathecal Drug Delivery System

Background: Complications associated with intrathecal pumps may be linked to the surgical procedure, the implanted device, or the medication itself. Case Reports: Three patients treated chronically with intrathecal clonidine presented with clonidine overdose due to inadvertent extravasation during the refilling procedure. All patients experienced loss of consciousness and severe systemic hypertension that required aggressive parenteral treatment. Discussion: Clonidine is an alpha‐2 agonist with a nearly 100% bioavailability after oral or rectal administration. With high plasma concentration secondary to massive systemic overdose, the specificity for the alpha‐2 receptor is lost and an alpha‐1 agonist activity predominates and causes marked hypertension. Management of clonidine overdose consists of supportive therapy guided by signs and symptoms. Conclusion: Inadvertent injection into the subcutaneous pocket rather than the reservoir is rare but very dangerous as the drug cannot be retrieved and massive doses are involved. Signs and symptoms of systemic overdose with drugs commonly used in implanted drugs delivery system should be well known to ensure early diagnosis and treatment.     

Guidelines for anaesthesiologist specialist training in pain medicine

The Section and Board of Anaesthesiology of the European Union of Medical Specialists aims (EUMS/UEMS) at harmonization of training of anaesthesiologists and at improvement of patient care throughout Europe. Pain medicine is considered to be an area of expertise in anaesthesiology although exclusivity is not claimed. The Section and Board has approved both a core syllabus for pain medicine to be part of the specialist training in anaesthesiology and an additional qualification in pain medicine following the completion of a 5 yr basic specialty training in anaesthesiology. These proposals were prepared by the Working Party on Pain Medicine of the Section and Board. It considers a multidisciplinary approach to pain to contribute to quality in care and has taken the initiative to set up a Multidisciplinary Joint Committee on Pain Medicine within the EUMS/UEMS, for which these guidelines define the area of expertise of anaesthesiology.     

Double-strand breaks may initiate the inversion mutation causing the Hunter syndrome

We have previously shown that patients with the Hunter syndrome frequently have suffered from a recombination event between the IDS gene and its putative pseudogene, IDS-2, resulting in an inversion of the intervening DNA. The inversion, which might be the consequence of an intrachromosomal mispairing, is caused by homologous recombination between sequences located in intron 7 of the IDS gene and sequences located distal of exon 3 in IDS-2. In order to gain insight into the mechanisms causing the inversion, we have isolated both inversion junctions in six unrelated patients. DNA sequence analysis of the junctions showed that all recombinations have taken place within a 1 kb region where the sequence identity is >98%. An interesting finding was the identification of regions with alternating IDS gene and IDS-2 sequences present at one inversion junction, suggesting that the recombination event has been initiated by a double-strand break in intron 7 of the IDS gene. The results from this study suggest that homologous recombination in man could be explained by mechanisms similar to those described for Saccharomyces cerevisiae. The results also have practical implications for diagnosis of patients with the Hunter syndrome.      

泽兰合剂质量标准研究

目的；建立泽兰合剂质量控制方法。方法：采用TLC对金银花，红花进行定性鉴别，HPLC测定绿原酸的含量。结果：TLC鉴别方法专属性强。含量测定绿原酸在0.2-1.0μg间有良好的线性关系。回收率为98.67%,RSD为2.19%。结论：本法简便，准确，重现性好，可作为该制剂的质量控制方法。