Methodological advances in the design of peptide-based vaccines

The tremendous advances in genomics, recombinant DNA technology, bioengineering and nanotechnology, in conjunction with the development of high-end computations, have been instrumental in the process of rational design of peptide-based vaccines. The use of peptide vaccines was limited owing to their inherent instability when systemically administered; however, advanced formulation techniques have been developed for their systemic delivery, thereby overcoming their degradation, clearance, cellular uptake and off-target effects. With the rise of sophisticated immunological predictors and experimental techniques, several methodological advances have occurred in this field. This review examines contemporary methods to identify and optimize epitopes, engineer their immunogenic properties and develop their safe and efficient delivery into the host.     

Hyaluronan-based delivery of therapeutic oligonucleotides for treatment of human diseases

Introduction: Oligonucleotide therapeutics such as antisense oligonucleotides and siRNA requires chemical modifications and nano-sized carriers to circumvent stability problems in vivo, to reach target tissues, and to overcome tissue and cellular barriers. Hyaluronic acid (HA), already utilized in drug delivery and tissue engineering, possess properties that are useful to solve these problems and achieve full potential of oligonucleotide therapeutics.

Areas covered: Complexes of oligonucleotide therapeutics with HA are discussed in terms of interactions providing the complexes formation and genes targeted by the therapeutics to cure diseases such as cancer, atherosclerosis, liver cirrhosis, and inflammation. The achieved therapeutic effects are rationalized as consequences of biodistribution, cell internalization and endosomal escape provided by HA.

Expert opinion: Design of electrostatic, coordination, and hydrophobic interactions as well as covalent conjugation between oligonucleotide drugs, HA macromolecules and intermediate ligands are crucial for carrier–cargo association and dissociation under different conditions to impart oligonucleotides stability in vivo, their accumulation in diseased organs, cellular uptake, and dissociation in cytoplasm intact. These are the delivery factors that provides eventual complex formation of oligonucleotide therapeutics with their mRNA, microRNA, or protein targets. Elucidation of the impact of structural parameters of oligonucleotide/HA complexes on their therapeutic effect in vivo is important for the future rational design of the delivery agents.     

Creutzfeldt-Jakob病与路易体痴呆脑电图表现的研究进展

社会老龄化加速使神经系统变性疾病成为神经病学一个备受关注的领域。EEG作为一项无创、廉价、可重复的检查手段,在神经系统变性疾病中已有广泛应用。目前已有多种特征性EEG被纳入相应疾病的诊断标准。本文从临床角度对Creutzfeldt-Jakob病(CJD)及路易体痴呆(DLB)的EEG表现、产生机制、鉴别诊断及临床应用作以总结,以期对诊断及鉴别诊断起提示作用。     

The effect of complexation with cyclodextrins on the antioxidant and antimicrobial activity of ellagic acid

Purpose: The aim of the paper was to develop the simple procedures for preparation of inclusion complexes of ellagic acid (EA) with cyclodextrins (CDs) and to investigate their antioxidant and antimicrobial activity.

Methods: The structural characterization was carried out using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and nuclear magnetic resonance (NMR) methods. The phase solubility technique was used to investigate the interactions between ‘host’ and ‘guest’ molecules and to estimate the molar ratio between them. The antioxidant and antimicrobial activity of EA and inclusion complexes were determined.

Results: The apparent stability constants were found to be 117?dm³ mol^?1 for the complex with β-CD and 161?dm³ mol^?1 for the complex with (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD). The results of phase-solubility studies showed that EA formed the inclusion complexes with CDs in the molar ratio of 1:1. The calculated half-maximal inhibitory concentration was 41.18?μg cm^?3 for butyl hydroxy toluene, 1.96?μg cm^?3 for EA, 0.88?μg cm^?3 for inclusion complex with HP-β-CD, and 1.27?μg cm^?3 for inclusion complex with β-CD.

Conclusion: The stability constants indicated the rapid release of EA from the inclusion complexes in the aqueous medium at 25?°C. The antioxidant activity of EA was increased, while the antimicrobial activity was preserved after complexation with CDs.     

手性金属配合物d,l-[Ni(phen)3]2+经Caco-2细胞单层模型的吸收转运

目的:研究手性金属配合物经Caco-2细胞单层转运吸收的手性选择性.方法:采用动力学研究方法,测定手性金属配合物跨Caco-2细胞单层的转运速率.结果:金属配合物的手性不同,导致金属配合物经Caco-2细胞单层的转运速率不同.结论:手性金属配合物经Caco-2细胞单层的转运吸收存在手性选择性的差异.     

High levels of serum glycans monovalent IgG immune complexes detected by dissociative ELISA in experimental visceral leishmaniasis

Visceral leishmaniasis (VL) is epidemic in Brazil with an increasing incidence of human cases and canine reservoirs, with host hypergammaglobulinemia. Conventional enzyme-linked immunosorbent assay (cELISA) based on several parasitic antigens is the main method for diagnosis and indication of treatment. Dissociative ELISA (dELISA) uses acidic treatment to free immunoglobulin G (IgG) from immune complexes, and its use revealed a significant positive fraction of suspected cases with negative serology. Looking for small molecules or haptens that block IgG antibodies, we purified by molecular exclusion chromatography, 1000–3000 MW molecules from promastigote soluble extract, mostly oligosaccharides comprising 6–13 sugar residues using MALDI-TOF analysis. Glycan-BSA complex (GBC) was constructed by conjugating promastigote glycans to BSA molecules, allowing their use in the solid support in cELISA or dELISA. Sera from experimentally infected hamsters showed higher levels of blocked monomeric IgG during infection, mostly against GBC, which was also present in lower concentrations in the promastigote soluble extract dELISA. Those data show that most of the specific monomeric IgG in serum are blocked by haptens composed by glycans produced by the parasite, better detected in the high dilution of sera in the dELISA assays. dELISA is a useful technique for detecting blocked monomeric antibodies that could have difficult clearance from blood, which could result in hypergammaglobulinemia.     

攻癌利水散外敷联合重组p53基因腺病毒治疗肺癌胸水30例

目的:观察攻癌利水散外敷联合重组p53基因腺病毒注射液胸腔灌注治疗对肺癌胸水的临床疗效。方法:将150例患者随机分为中药组、p53组、中药+p53组、顺铂组、空白组,每组30例。用药2疗程后观察临床疗效、毒副作用与生活质量的改变情况。结果:总有效率中药+p53组最高,与其他各组比较,差异均有统计学意义(P0.05)。白细胞下降及消化道反应情况顺铂组较明显,与其他各组比较,差异有统计学意义(P0.05);发热p53组较明显,与其他各组比较,差异有统计学意义(P0.05)。PKS评分治疗后中药+p53组升高最明显,与其他各组比较,差异有统计学意义(P0.05)。结论:攻癌利水散外敷联合重组p53基因腺病毒注射液胸腔灌注治疗肺癌胸水临床疗效显著,且不良反应小。     

Competitive adsorption versus surface complexation as models for the simultaneous adsorption of metal complexes and free ligands

A statistical thermodynamical approach to the study of anion-induced adsorption of Cd(II) from halide solutions is presented. The simultaneous adsorption of metal complex and ligand is introduced in the isotherms by considering two possible mechanisms — competitive adsorption and surface complexation. These isotherms have been tested for the system Cd(II) in KBr at several ionic strengths. The experimental surface excesses of Cd(II) calculated from single-step chronocoulometry can be simulated, giving an explanation for the desorption of the metal complex at positive potentials. Also, the change in ligand adsorption promoted by the adsorption of the metal complex has been calculated. Both approaches lead to the conclusion that the anionic tricoordinate metal complex CdBr₃^? and the tetracoordinate CdBr₄^2? are the absorbed species on the electrode surface, with CdBr₄^2? dominating at higher bromide concentrations.     

Steady-state voltammetry for the reduction of labile metal complexes in the absence and presence of different concentrations of supporting electrolyte1

Steady-state voltammetry for the reduction of labile complexes of lead, cadmium and mercury, in the absence of deliberately added supporting electrolyte and with different concentrations of supporting electrolyte, has been studied at mercury (lead and cadmium) and platinum disc (mercury) microelectrodes. The effects of ionic strength and nature of an inert electrolyte on the migrational component, which usually adds to diffusion in the mass transport in solutions with low electrolyte, have been examined. The results obtained have demonstrated that the ratio of limiting current at different concentrations of supporting electrolyte to diffusive limiting current I_lm/I_ld, depended not only on the charge of the free ion, but also on the amount of labile complexes formed between the metal ion with ligands which may arise from the counter-ion accompanying the metal in its starting salt, from small amounts of supporting electrolyte and from the autoprotolysis of water, i.e., OH^?. Moreover, the I_lm/I_ld ratio is affected by the background electrolyte, which is almost unavoidable in water, and by the hydrolysis of the metal ion which yields protons. A comprehensive theoretical equation, based on already known treatments, has been also derived to predict the limiting current ratios in the presence of all the effects cited above.