Application of the Electrotopological State Index to QSAR Analysis of Flavone Derivatives as HIV-1 Integrase Inhibitors

Purpose. A QSAR study based on electrotopological state (E-state) indices was conducted for a series of flavone HIV-1 integrase inhibitors to guide drug design. Methods. E-state indices formulated to encode electronic and topological information for each skeletal atom in a molecule (Kier and Hall Pharm. Res. 7:801–807 (1990)) were calculated using the Molconn-X program, and partial least squares (PLS) multivariate regression was used to derive QSAR models. Results. Predictive models with correlation coefficients (r²) of 0.98 (3 PLS components) and 0.99 (5 PLS components) and corresponding cross-validated correlation coefficients (c.v. r²) of 0.51 and 0.73, were obtained for inhibition of cleavage and integration, respectively, with one molecule omitted from the analysis. Conclusions. E-state indices at C6, C3, C5, C5, and O4 were found to be more important for prediction of activity than those for any of the other 12 flavone skeletal atoms that are common to the molecules in the data set.     

Electrophysiological determination of the refractive state of the eye of the opossum

The refractive state of the eye of the South American opossum Didelphis marsupialis aurita was investigated with electrophysiological techniques. Using adult specimens, trapped from the wild, averaged cortical evoked responses were recorded from the region of projection of the central visual field. Stimuli consisted of a phase reversal of a square wave grating generated on a CRO screen, with luminance of 2.4 cd/m2 and contrast 0.84. The refractive state of the eye was altered by means of trial lenses and the amplitude of the cortical responses thus obtained compared to those obtained with no lens (control values). Refraction "tuning curves" were determined for each animal. The average refractive state was found to be -2.27 D indicating that this species when raised in its habitat shows, at low ambient luminosity, some degree of myopia. Determination of the Contrast Sensitivity Function indicate that induced ametropias lead to a reduction of the cut-off value of the spatial frequency and a loss of contrast sensitivity.     

Effect on electroencephalogram of chewing flavored gum

The objective of the present study was to evaluate the effect on the electroencephalogram (EEG) of a chewing gum with and without our prepared new flavor. Electroencephalograms were obtained after the following three tests: chewing pure gumbase with sucrose (standard gumbase), chewing flavored standard gum and the inhalation of flavored aromatic oil. As the control, we used the pre-stimulus control EEG record without a stimulus. We examined the relationship between the pre-stimulus control record and the post-stimulus record using the changes of power in four bands. Chewing the standard gumbase led to an increase in the alpha wave and a decrease in the beta wave. Chewing the flavored standard gum and inhaling the flavored aromatic oil each increased the alpha and beta waves. In addition, chewing the flavored standard gum led to a change in the ratio of theta wave in the frontal area. The difference in the theta, alpha and beta bands in chewing gum with and without the added flavor suggested that the flavor as well as chewing could induce concentration with a harmonious high arousal state in brain function.     

Objective assessment of auditory thresholds in noise‐induced hearing loss using steady‐state evoked potentials

Objective assessment of auditory thresholds in noise‐induced hearing loss using steady‐state evoked potentials The purpose of this study is to evaluate whether steady‐state evoked potential (SSEP) can be used for objective estimation of auditory thresholds in patients with noise‐induced hearing loss (NIHL). Eleven subjects (22 ears) with a characteristic audiometric notch between 3000 and 6000 Hz participated in this study. Both pure‐tone thresholds and SSEP thresholds were obtained for each ear of all subjects. The correlation of SSEP thresholds and pure‐tone thresholds was assessed. The results show that SSEP thresholds predicted pure‐tone thresholds with correlation coefficients (r) of 0.86, 0.92, 0.94 and 0.95 at 500, 1000, 2000 and 4000 Hz respectively. Typically, the SSEP thresholds overestimate the pure‐tone thresholds by 10–20 dB, but they closely reflect the configuration of the audiogram. The strength of the relationship between SSEP and pure‐tone thresholds increased with increasing frequency and increasing degree of hearing loss. In conclusion, SSEP can be used as a reliable and objective tool to assess auditory thresholds in patients with noise‐induced hearing loss with high‐frequency dips.     

Synthesis of substrates and inhibitors of botulinum neurotoxin type A metalloprotease*

Abstract: Botulinum neurotoxin (BoNT) metalloproteases and related proteases are the most selective proteases known. X‐ray crystal structures suggest that the active sites of the native enzymes exist in catalytically incompetent forms that must be activated by substrate binding. In order to characterize the postulated substrate‐induced conformational changes for enzyme activation, we synthesized a series of transition‐state analog inhibitors in which the dipeptide cleavage site is replaced by tetrahedral intermediate analogs within the minimal substrate peptide sequence. In this paper, we report our efforts to design inhibitors of BoNT/A metalloprotease. We confirm that an effective substrate sequence for BoNT/A metalloprotease is a 17‐mer peptide corresponding to residues 187–203 of SNAP‐25. A more stable substrate, Nle²⁰²SNAP‐25 [187–203] was synthesized in order to develop an assay for proteolytic activity of BoNT/A metalloprotease that can be used to monitor time‐dependent inhibition. α‐Thiol amide analogs of Gln‐197 were incorporated via solid‐phase peptide synthesis into both 17‐mer minimal peptide substrate sequences. The synthesis, characterization and inhibition kinetics for the α‐thiol amide analogs of holotoxin A substrate are described. These substrate‐derived inhibitors were shown to be submicromolar inhibitors of BoNT/A catalytic activity.     

关于亚健康状态的躯体、心理和社会因素的调查研究

目的：阐明亚健康的躯体、心理、社会多方面的影响。方法：采用问卷评定量表调查表，向每个对象发放问卷评定量表，并由本人自己填写。结果：亚健康患者心理社会应激和宽容者与症状的发生有关，其中心理社会应激对症状的发生影响最大，宽容者自己对付不良身体状态的能力较高，不易发生身体症状。结论：使用躯体、生理、社会因素的测定来掌握“亚健康状态”，寻找发病原因，对患者进行教育非常必要。     

小剂量肝素治疗肺癌患者血栓前状态的临床研究

报道７５例中、晚期肺癌血栓前状态Ｄ－二聚体在治疗过程中的变化情况。小剂量肝素加化疗加／或放疗治疗组４０例，Ｄ－二聚体转正常３２例、有效率（８０％）。化疗加／或放射治疗（无肝素组）３５例，Ｄ－二聚体转正常６例，有效率１７．１％（Ｐ＜０．０１）。观察结果表明：小剂量肝素治疗中、晚期肺癌血栓前状态是一种有效、安全的方法。     

论辨证论治

辨证论治是中医学理论体系的特色之一，也是中国传统科学特征在医学中的体现。1．辨证理路的形成与中国传统文化以辨证的思维方式，《周易》哲学的变易观念，传统科技重视时间因素以时间统摄空间，以及承袭针灸治疗的操作习惯等有关。2．辨证论治的特点，主要体现在思维方式、框架体系、辨析内容、论治原则和操作技巧诸方面。3．辨证论治是建立在理论模型化的证候与“辨”的思维推理基础之上，辨证论治的境界与医生的学养、经验和创造性有关。辨证论治要提高、要发展、要突破。     

2004年武汉地区医院用药状况分析

目的：了解2004年度武汉地区的用药状况.方法：根据HPDIS提供的资料,回顾性统计分析购药金额、用药频度、每日费用及年平均增长率.结果：本年度购药金额与去年相比增幅明显,购药金额列前20名药品用药频度呈上升趋势,日费用有所下降.结论：武汉地区医院用药呈现稳定、健康增长,药品市场具有良好发展空间.     

CT图像中噪声产生机理与维修

本文重点阐述和分析了CT图像中的几种噪声产生的原因和对图像的影响,并结合笔者多年的维修经验,从理论和实际相结合,介绍了几种实用的维修方法,提出了减小噪声提高图像质量的有效措施。