神经梅毒的诊断与治疗（附23例分析）

观察神经梅毒的临床特点,以提高对神经梅毒的诊断与治疗水平。回顾性分析哈尔滨医科大学附属第一医院2005年1月至2010年12月收治的23例神经梅毒患者的临床资料。神经梅毒患者男17例（73.9%）,女6例（26.1%）,男女比约为2.8∶1;年龄27~71岁,平均年龄43.1岁。本组首发症状：麻痹性痴呆（7例）、精神异常（3例）、急性脑梗死（3例）、癫痫（2例）、脊髓病变（2例）、颅高压（2例）、周围神经损害（2例）、脑神经损害（1例）、无症状性神经梅毒（1例）。23例患者血清及脑脊液快速血浆反应素实验及梅毒螺旋体血凝试验均呈阳性反应。颅脑电子计算机断层扫描（CT）和/或磁共振成像（MRI）检查多表现为额叶、顶叶、颞叶、基底节等多发病变。本组患者经大剂量青霉素治疗后病情有显著改善20例,死亡1例,自动出院2例。神经梅毒的临床表现复杂多样,神经系统各部位均可受累,诊断依靠病史及临床表现、实验室血清及脑脊液梅毒抗体检测,误诊率高,应早期诊断,诊断后应进行规范治疗,早期治疗效果较好。     

Treatment of Biogas Produced in Anaerobic Reactors for Domestic Wastewater: Odor Control and Energy/Resource Recovery

Anaerobic municipal wastewater treatment in developing countries has important potential applications considering their huge lack of sanitation infrastructure and their advantageous climatic conditions. At present, among the obstacles that this technology encounters, odor control and biogas utilization or disposal should be properly addressed. In fact, in most of small and medium size anaerobic municipal treatment plants, biogas is just vented, transferring pollution from water to the atmosphere, contributing to the greenhouse gas inventory. Anaerobic municipal sewage treatment should not be considered as an energy producer, unless a significant wastewater flow is treated. In these cases, more than half of the methane produced is dissolved and lost in the effluent so yield values will be between 0.08 and 0.18 N m³ CH₄/kg COD removed. Diverse technologies for odor control and biogas cleaning are currently available. High pollutant concentrations may be treated with physical-chemical methods, while biological processes are used mainly for odor control to prevent negative impacts on the treatment facilities or nearby areas. In general terms, biogas treatment is accomplished by physico-chemical methods, scrubbing being extensively used for H₂S and CO₂ removal. However, dilution (venting) has been an extensive disposal method in some small- and medium-size anaerobic plants treating municipal wastewaters. Simple technologies, such as biofilters, should be developed in order to avoid this practice, matching with the simplicity of anaerobic wastewater treatment processes. In any case, design and specification of biogas handling system should consider safety standards. Resource recovery can be added to anaerobic sewage treatment if methane is used as electron donor for denitrification and nitrogen control purposes. This would result in a reduction of operational cost and in an additional advantage for the application of anaerobic sewage treatment. In developing countries, biogas conversion to energy may apply for the clean development mechanism (CDM) of the Kyoto Protocol. This would increase the economic feasibility of the project through the marketing of certified emission reductions (CERs).     

Binding cavities and druggability of intrinsically disordered proteins

To assess the potential of intrinsically disordered proteins (IDPs) as drug design targets, we have analyzed the ligand-binding cavities of two datasets of IDPs (containing 37 and 16 entries, respectively) and compared their properties with those of conventional ordered (folded) proteins. IDPs were predicted to possess more binding cavity than ordered proteins at similar length, supporting the proposed advantage of IDPs economizing genome and protein resources. The cavity number has a wide distribution within each conformation ensemble for IDPs. The geometries of the cavities of IDPs differ from the cavities of ordered proteins, for example, the cavities of IDPs have larger surface areas and volumes, and are more likely to be composed of a single segment. The druggability of the cavities was examined, and the average druggable probability is estimated to be 9% for IDPs, which is almost twice that for ordered proteins (5%). Some IDPs with druggable cavities that are associated with diseases are listed. The optimism versus obstacles for drug design for IDPs is also briefly discussed.     

Analysis of the inhibition potential of zosuquidar derivatives on selected bacterial and fungal ABC transporters

Abstract

The increasing number of multidrug-resistant pathogenic microorganisms is a serious public health issue. Among the multitude of mechanisms that lead to multidrug resistance, the active extrusion of toxic compounds, mediated by MDR efflux pumps, plays an important role. In our study we analyzed the inhibitory capability of 26 synthesized zosuquidar derivatives on three ABC-type MDR efflux pumps, namely Saccharomyces cerevisiae Pdr5 as well as Lactococcus lactis LmrA and LmrCD. For Pdr5, five compounds could be identified that inhibited rhodamine 6G transport more efficiently than zosuquidar. One of these is a compound with a new catechol acetal structure that might represent a new lead compound. Furthermore, the determination of IC₅₀ values for rhodamine 6G transport of Pdr5 with representative compounds reveals values between 0.3 and 0.9 μM. Thus the identified compounds are among the most potent inhibitors known for Pdr5. For the ABC-type efflux pumps LmrA and LmrCD from L. lactis, seven and three compounds, which inhibit the transport activity more than the lead compound zosuquidar, were found. Interestingly, transport inhibition for LmrCD was very specific, with a drastic reduction by one compound while its diastereomers showed hardly an effect. Thus, the present study reveals new potent inhibitors for the ABC-type MDR efflux pumps studied with the inhibitors of Pdr5 and LmrCD being of particular interest as these proteins are well known model systems for their homologs in pathogenic fungi and Gram-positive bacteria.     

Isolation and characterisation of nuclear mutants with enhanced mitochondrial mutability in the fission yeast Schizosaccharomyces pombe

In this paper we report the isolation and preliminary characterisation of nuclear mutants with increased mitochondrial mutability in fission yeast. Screening of about 2000 clones after nitrosoguanidine mutagenesis led to the isolation of ten mutator mutants. For one of them (mut-1) we show that the mutation is chromosomally encoded. The activity of the mutator is restricted to the mitochondrial genome, since it increases the mutation rate to mitochondrially encoded drug resistance considerably, whereas the mutability of nuclear genes is not altered.     

菊芋HtCCR1基因的克隆与表达分析

肉桂酰辅酶A还原酶(cinnamoyl-CoA reductase,CCR)是木质素合成代谢的关键酶。该研究以菊芋(Helianthus tuberosus L.)‘廊芋8号’为材料,克隆到1个菊芋的CCR基因,命名为HtCCR1(GenBank登录号为MN205540),其开放阅读框(ORF)长975bp,编码324个氨基酸,其中含有FR_SDR_e保守结构域。系统进化分析表明,HtCCR1与向日葵CCR蛋白(XP_021989763.1)共聚于一支,二者亲缘关系最近。实时定量PCR分析表明,HtCCR1基因在菊芋茎和叶中的表达量显著高于在根和块茎中;盐(150mmol·L-1 NaCl)胁迫处理6、12和24h后,处理组HtCCR1基因的表达量均显著高于对照组;干旱(20%PEG6000)胁迫6和12h后,处理组HtCCR1基因的表达较对照组均显著上调。成功构建pET-28a-HtCCR1原核表达载体,转化大肠杆菌BL21(DE3)并诱导出了符合预期大小的蛋白,表明HtCCR1重组蛋白已成功表达。该研究结果为进一步研究HtCCR1基因的功能及利用基因工程手段调节菊芋中木质素的生物合成奠定了基础。     

Biological characteristics of dengue virus and potential targets for drug design

Dengue infection is a major cause of morbidity in tropical and subtropical regions, bringing nearly 40% of the world population at risk and causing more than 20,000 deaths per year. But there is neither a vaccine for dengue disease nor antivirai drugs to treat the infection. In recent years, dengue infection has been particularly prevalent in India, Southeast Asia, Brazil, and Guangdong Province, China. In this article, we present a brief summary of the biological characteristics of dengue virus and associated flaviviruses, and outline the prowess on studies of vaccines and drugs based on potential targets of the dengue virus.     

混凝复配剂的制备及其污水处理效果

采用静态实验遴选不同种硅藻土,进而研究其与常用混凝剂的最佳组合及复配比,考察其中几种复配剂在一定条件对城市污水的处理效果。实验结果表明:硅藻土和混凝剂组成的复配剂具有强化混凝作用;氯化铝、硫酸亚铁和高分子絮凝剂与硅藻土分别在1:9,1:11,和1:9的配比时制备复配剂处理生活污水的效果最佳。     

Screening of Drugs That Suppress Ste11 MAPKKK Activation in Yeast Identified a c-Abl Tyrosine Kinase Inhibitor

The yeast MAPKKK Ste11 activates three MAP kinase pathways, including pheromone signaling, osmosensing, and pseudohyphal/invasive growth pathways. We identified two chemical compounds, BTB03006 and GK03225, that suppress growth defects induced by Ste11 activation in diploid yeast cells. BTB03006, but not GK03225, was found to suppress growth defects induced by both α-factor and Ste4 G_β overexpression in the pheromone signaling pathway, suggesting that GK03225 is an osmosensing pathway-specific inhibitor. We also performed genome-wide suppressor analysis for Ste11 activation, using a yeast deletion strains collection, and identified PBS2 and HOG1, and several genes associated with chaperone functions, which represent potential target proteins of the drugs screened from Ste11 activation. GK03225 possesses an Iressa-like quinazoline ring structure, and its chemical analog, 11N-078, suppresses c-Abl human tyrosine kinase activity. These results suggest that drug screening in yeast can identify human tyrosine kinase inhibitors and other drugs for human diseases.