Discovery of Novel Multiacting Topoisomerase I/II and Histone Deacetylase Inhibitors

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Discovery of Imidazo[1,2-α][1,8]naphthyridine Derivatives as Potential HCV Entry Inhibitor

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AaeAP1 and AaeAP2: Novel Antimicrobial Peptides from the Venom of the Scorpion,Androctonus aeneas: Structural Characterisation,Molecular Cloning of Biosynthetic Precursor-Encoding cDNAs and Engineering of Analogues with Enhanced Antimicrobial and Anticancer Activities

The main functions of the abundant polypeptide toxins present in scorpion venoms are the debilitation of arthropod prey or defence against predators. These effects are achieved mainly through the blocking of an array of ion channel types within the membranes of excitable cells. However, while these ion channel-blocking toxins are tightly-folded by multiple disulphide bridges between cysteine residues, there are additional groups of peptides in the venoms that are devoid of cysteine residues. These non-disulphide bridged peptides are the subject of much research interest, and among these are peptides that exhibit antimicrobial activity. Here, we describe two novel non-disulphide-bridged antimicrobial peptides that are present in the venom of the North African scorpion, Androctonus aeneas. The cDNAs encoding the biosynthetic precursors of both peptides were cloned from a venom-derived cDNA library using 3''- and 5''-RACE strategies. Both translated precursors contained open-reading frames of 74 amino acid residues, each encoding one copy of a putative novel nonadecapeptide, whose primary structures were FLFSLIPSVIAGLVSAIRN and FLFSLIPSAIAGLVSAIRN, respectively. Both peptides were C-terminally amidated. Synthetic versions of each natural peptide displayed broad-spectrum antimicrobial activities, but were devoid of antiproliferative activity against human cancer cell lines. However, synthetic analogues of each peptide, engineered for enhanced cationicity and amphipathicity, exhibited increases in antimicrobial potency and acquired antiproliferative activity against a range of human cancer cell lines. These data clearly illustrate the potential that natural peptide templates provide towards the design of synthetic analogues for therapeutic exploitation.     

Development of a new ferulic acid certified reference material for use in clinical chemistry and pharmaceutical analysis

This study compares the results of three certified methods, namely differential scanning calorimetry (DSC), the mass balance (MB) method and coulometric titrimetry (CT), in the purity assessment of ferulic acid certified reference material (CRM). Purity and expanded uncertainty as determined by the three methods were respectively 99.81%, 0.16%; 99.79%, 0.16%; and 99.81%, 0.26% with, in all cases, a coverage factor (k) of 2 (P=95%). The purity results are consistent indicating that the combination of DSC, the MB method and CT provides a confident assessment of the purity of suitable CRMs like ferulic acid.Abbreviations: ASTM, American Society for Testing and Materials; CRM, certified reference material; CT, coulometric titrimetry; DAD, diode-array detector; DSC, differential scanning calorimetry; EDQM, European Directorate for Quality Medicine; GUM, Guide to the Expression of Uncertainty in Measurement; ISO, International Organization for Standardization; MB, mass balance; RM, reference material; SI, International System of Units; WHO, World Health OrganizationKEY WORDS: Differential scanning  calorimetry, Mass balance, Coulometric titrimetry, Certified reference  material, Uncertainty, Ferulic acid     

Chromopeptide A,a highly cytotoxic depsipeptide from the marine sediment-derived bacterium Chromobacterium sp. HS-13-94

A bicyclic depsipeptide, chromopeptide A (1), was isolated from a deep-sea-derived bacterium Chromobacterium sp. HS-13-94. Its structure was determined by extensive spectroscopic analysis and by comparison with a related known compound. The absolute configuration of chromopeptide A was established by X-ray diffraction analysis employing graphite monochromated Mo K_α radiation (λ=0.71073 Å) with small Flack parameter 0.03. Chromopeptide A suppressed the proliferation of HL-60, K-562, and Ramos cells with average IC₅₀ values of 7.7, 7.0, and 16.5 nmol/L, respectively.KEY WORDS: Chromopeptide A, Bacterium, Depsipeptide, Absolute configuration, Marine-derived, Sediments, Cytotoxicity, Chromobacterium sp.     

聚乙二醇滴眼液治疗干眼症30例

目的探讨聚乙二醇滴眼液治疗干眼症的临床疗效。方法选择2011年10月至2013年4月收治的干眼症患者60例(120只眼),随机分成对照组30例(60只眼),治疗组30例(60只眼)。对照组给予热敷、睑板腺按摩及玻璃酸钠滴眼液,4次/日,治疗组同时联合聚乙二醇滴眼液,4次/日。结果治疗后1,2,4周较治疗前泪膜破裂时间及泪液分泌试验(SchirmerⅠ)均明显增加(P<0.05);治疗组和对照组比较,泪膜破裂时间显著延长,比较差异有统计学意义(P<0.05);SchirmerⅠ治疗组较对照组明显增加,但无显著差异(P>0.05)。结论聚乙二醇滴眼液治疗干眼症疗效显著,可有效促进患者泪膜恢复、缓解干眼症状,保持泪膜的稳定性。     

帕瑞昔布超前镇痛对腹部手术患者围术期应激反应及术后镇痛的影响

目的观察帕瑞昔布钠超前镇痛对腹部手术患者围术期应激反应和术后镇痛的影响。方法选择美国麻醉医师协会(ASA)Ⅰ~Ⅱ级行腹部手术患者100例,随机观察组和对照组,每组50例。两组患者分别在术前30 min单次肌肉注射帕瑞昔布钠40 mg和相同容积的0.9%氯化钠注射液2 m L。两组患者分别在注射前10 min(T1)、手术开始后30 min(T2)、60 min(T3)、术毕即刻(T4)及术后6 h(T5)、12 h(T6)抽取静脉血样,测定各时点肾上腺素(E)、去甲肾上腺素(NE)、皮质醇(Cor)、促肾上腺皮质激素(ACTH)的血浆浓度。结果与对照组比较,观察组在T2及T3时点血浆E和NE浓度显著降低(P<0.01),在T2,T3,T4时点血浆Cor浓度显著降低(P<0.01),在T2,T3,T 4,T5时点血浆ACTH浓度显著降低(P<0.01)。与对照组比较,观察组在术后1,2,6,12,24 h疼痛视觉模拟评分(VAS)降低(P<0.05)。结论腹部手术前预先给予帕瑞昔布钠可产生良好的超前镇痛效果,减少手术患者围术期应激激素的释放,提高术后镇痛质量,有利于术后恢复。     

锁定钢板与动力髋螺钉治疗老年股骨粗隆粉碎性骨折疗效分析

目的：评价锁定钢板治疗股骨粗隆粉碎性骨折的临床疗效。方法对我科2009年至2013年就诊的115例老年股骨粗隆粉碎性骨折患者随机分为：观察组58例应用锁定钢板;对照组57例应用动力髋螺钉,手术后通过至少6个月的观察和随访并进行Sanders髋关节等级评分,比较分析其临床治疗效果。结果观察组总满意率为96.6%（56/58）,对照组78.9%（51/57）,有统计学意义（P＜0.01）。结论锁定钢板治疗股骨粗隆粉碎性骨折疗效比较确切,具有良好的临床应用价值,值得借鉴和推广。