3-芳基-4(3H)-喹唑酮衍生物J35构象研究

采用MNDO法计算得到安眠酮类似物-J35的优势构象,所得结果与紫外、核磁共振数据相符。进一步研究表明,不同构象具有不同的分子轨道指数,因此建议:运用分子轨道指数研究药物的构效关系时,应采用药效构象的分子轨道指数;在不知道药效构象的情况下,可采用优势构象的分子轨道指数。     

肟类胆碱酯酶重活化剂进入脑的探讨

肟类胆碱酯酶重活化剂目前常用的有氯磷定(PAM)、双磷定(TMB_4)和双复磷(L(?)H-6)。它们是季铵化合物,水溶性大,脂溶性小,其穿透血脑屏障的能力,及在中枢神经系统重活化被有机磷酸酯抑制的胆碱酯酶的作用一直有争论,至今仍是一个比较活跃的研究课题。1976年BodorN.等合成了氯磷定的前体(Prodrug)Pro-2-PAM·Cl(二氢氯磷     

二苯并[b，e]氧（硫）杂■羟基羧酸酯类抗胆碱能化合物的构象分析

用系统构象搜索方法计算得到了６，１１二氢二苯并［ｂ，ｅ］氧（硫）杂１１羟基１１羧酸酯类抗胆碱能化合物在不同构型时的低能构象。通过对这些构象能的分析、比较，从中确定出每种化合物能量最低的优势构象，并发现在含有哌啶醇的羧酸酯中，酯键处于直立键时的构象能要低于处于平伏键时的构象能，即酯键处于直立键时的构象更为稳定     

一类“非季铵型重活化剂”的构效关系及其作用机理的研究

乙酰胆碱酯酶的叔胺型重活化剂一直被认为是比较理想的重活化剂,但是,由于缺少明确的理论指导,国际上探索了20多年仍未见有明显进展。本研究对文献报道的“非季铵型”重活化剂,通过分子力学(MMPM程序)和量子化学(MNDO程序)计算,进行构效关系分析,讨论其作用机理,并根据我们自己的重活化剂作用机理,设计了新型重活化剂的基本分子结构,可供药物合成参考。     

梭曼抗毒剂HGG类化合物定量构效关系的研究

梭曼膦酰化胆碱酯酶很易脱烷基,发生老化,一般肟类重活化剂较难使之重活化。近年来,合成了大量肟基取代的不对称双吡啶季铵盐,其中一些化合物对抗梭曼中毒有效。至于构效关系方面的分析,一般只涉及定性讨论。在一系列肟类双吡啶季铵盐研究中发现,对抗VX、沙林及梭曼中毒,肟基取代在吡啶环2-位上要比取代在4-位的化合物有较高的抗毒效价。为此,文献报道的双吡啶季铵盐大都属于2肟取代的化合物。对于第2个吡啶环上取代基位置,Moksimovic等指出3-取代的化合物比4-位异构体     

二苯并[b,e]氧（硫）杂Zhuo羟基羧酸酯类抗胆碱能化合物的构…

用系统构象搜索方法计算得到了６，１１－二氢－二苯并（ｂ，ｅ）氧（硫）杂Ｚｈｕｏ－１１羟基－１１－羧酸酯类抗胆碱能化合物在不同构型时的低能构象，通过对这些构象能的的分析，比较，从中确定出每种化合物能量最低的优势构象，并发现在含有哌啶醇的羧酸酯中，酯键处于直立键时的构象能要低处于处于平伏键时的构象能，即酯键处于直立键时的构象更为稳定。     

新型叔胺型重活化剂的研制及其意义

自80年代以来,难防难治的梭曼已成为世界防化研究的主攻目标。其主要原因是由于梭曼中毒酶老化快,梭曼结构中频哪基的空间位阻障碍着重活化剂的效能和梭曼的毒性强等。为此,对梭曼中毒酶重活化剂的研究是至关重要的。对神经性毒剂梭曼的防治水平可作为衡量一个国家防化医学研究水平的标志。 50年代推出的肟类重活化剂如2—PAM(含不同盐)和TMB—4等,抗梭曼无效,对梭曼中毒酶也无重活化作用。70年代出现一系列“H”肟类季铵盐化合物是文献报道的治疗梭曼中毒很有效的一类重活化剂,其中HI-6疗效最佳并对膈肌等梭曼中毒酶有确切的部分重活化作用。     

抗胆碱能药物的构象研究 Ⅰ.阿托品类茄科生物碱的分子力学研究

用分子力学研究了颠茄生物碱类包括阿托品、东茛菪碱、山茛菪碱和樟柳碱等抗胆碱能药物的构型构象,说明了天然茄科植物中只存在这些分子某种异构体的原因,推测了药物分子与胆碱能毒蕈碱(M)受体四点作用方式,同时考察了抗胆碱能药物中枢与外周作用的相关性。     

心电基线漂移去除方法的比较研究

基线漂移可严重影响心电信号的分析与处理.滤波法和拟合基漂法是去除心电基线漂移的两类主要算法.本文讨论了形态滤波、中值滤波、线性相位FIR滤波、小波变换、形态和小波相结合、中值滤波和小波相结合等去除基漂的滤波方法,并与导数法与坐标法这两类基漂拟合方法进行了对比.实验结果表明,滤波法实现简单,但精度较低;分段拟合法去除基漂的效果更好,有自适应的特性而且失真较小.无论是实时性还是准确性,基漂拟合法都比滤波法更有优势;但某些场合下,基漂拟合点的提取十分困难,此时只能使用滤波法.本文比较了基漂去除的常用方法,从而为基漂去除方法的选择提供参考.     

从普罗帕酮的旋光扭转谈对映体命名的旋光旋识

通过考察普罗帕酮对映体及其盐酸盐的比旋光度,强调了旋光方向与对映体构型之间关系的不确定性,建议对映体的命名中不标识旋光方向,而应仅采用构型标示。     

肟类重活化剂对抗氧化乐果抑制离体大鼠膈肌的研究

在离体大鼠膈神经－膈肌标本（膈ＮＭＰ）上观察了和的肟类重活化剂氯磷定碘磷定、双复磷和ＨＩ－６对抗氧化氯对标本的抑制作用，发现４种药物在对抗氧化乐果抑制离体大鼠膈ＮＭＰ的作用中均有对中毒酶的重活化作用，其强弱排序为：双复磷〉氯磷定、碘磷定〉ＨＩ－６。ＨＩ－６具有较强的直接生理对抗作用。     

An interspecies comparison of the phagocytosis and dissolution of 241AmO2 particles by rat, dog and monkey alveolar macrophages in vitro.

Because of the role that alveolar macrophages (PAM) play in the pulmonary clearance of inhaled particles via mechanical transport and dissolution, understanding the uptake and dissolution of particles by these cells might provide insight into the mechanisms of particle dissolution in lungs of various species and hence facilitate the extrapolation of animal data to humans. Therefore, experiments were conducted to study the phagocytosis and dissolution of 241AmO2 particles by rat, dog and monkey PAM in vitro. Rat, dog and monkey PAM were exposed for up to 72 h to 0.19, 0.93 or 4.6 kBq/ml 241Am, after which cell viability was determined. The 241Am concentration, 4.63 kBq/ml, was used for the phagocytosis and dissolution experiments. The phagocytosis and dissolution of 241AmO2 particles were followed up to 20 and 72 h, respectively. Dog and monkey PAM took up 241AmO2 particles at similar rates, whereas rat PAM phagocytosed only 60% of the amount phagocytosed by dog and monkey PAM at 20 h. The PAM of the three species dissolved 241AmO2 particles at similar rates; 8-10% was dissolved by 72 h. The results of the 241AmO2 uptake in vitro may reflect in vivo situations, where the differences in uptake seen in vitro would probably diminish at later times after exposure. The dissolution results imply that the dissolution of 241AmO2 particles by alveolar macrophages of the three species might be species-independent. This, at least, might be true for dog and monkey, where in vivo data have shown that 241AmO2 was translocated similarly in both species. Finally, the alveolar macrophage culture system provides a useful simulation to investigate uptake and dissolution of inhaled particles.     

A simple method for quantitative evaluation of the missing area of the anterior glenoid in anterior instability of the glenohumeral joint

OBJECTIVE: The objective of this study was to describe and validate a simple method to quantitatively calculate the missing area of the anterior part of the glenoid in anterior glenohumeral instability. MATERIALS AND METHODS: The calculations were developed from three-dimensional (3D)-reconstructed computerized tomography en face images of the glenoid with "subtraction" of the humeral head in 13 consecutive cases with known anterior glenohumeral joint instability diagnosed by history and clinical examination. The inferior portion of the glenoid was approximated to a true circle whose center was determined by means of a femoral head gauge. The eroded anterior area was calculated as the ratio between the depth (a perpendicular line from the center of the circle to the eroded edge of the anterior glenoid) and the radius of the inferior glenoid circle. This data was then compared to the results obtained by two additional different methods: direct computerized measurements of the missing area and direct computerized measurement of the ratio between the radius and depth, on two dimensional computed tomography (CT) en face view reconstructions of the glenoid. RESULTS: We provide a function that correlates the ratio between depth and radius of the inferior glenoid circle and the area of the missing anterior glenoid. The results obtained by three different methods were comparable. Simple trigonometric calculations showed that a 5% area defect corresponds to 0.8 (12.5%) of the radius of the inferior glenoid, while a 20% area defect corresponds to 0.5 (50%) of the same radius (Table 1). Table 1 Results according to each different method Patient Sex Side CA1 MA1 PAM1 R2 D2 PAM2 R3 D3 PAM3 1 M R 738 19.1 2.58 15.1 13.4 2.45 16 14 2.6 2 M R 462.6 30.5 6.59 11.9 9.7 4.83 16 10 12.97 3 F L 359 24.5 6.82 17 11.8 9.86 11.8 17 9.86 4 M L 522 59.4 11.37 12.7 9.1 8.95 16 10 12.97 5 M L 670 93.1 13.89 13.6 7.6 16.84 16 9 16.31 6 M R 659 137.5 20.8 14.3 7.1 20.10 20 8 25.23 7 M L 520 137 26.34 11.6 5.1 23.49 16 8 19.55 AVG 12.63 12.36 14.21 SD 8.46 7.92 7.20 CA1 Area of circle directly measured by MPR software, MA1 missing area of circle measured by MPR software, PAM1 calculated (100 x MA1/CA1) percentage area missing for method 1, R2 radius of the circle measured by MPR software, D2 depth from the missing edge to the center of the circle measured by MPR software, PAM2 calculated Percentage area missing from R2 and D2 using the function "q" (Appendix), R3 radius of the circle measured with a femoral gauge, D3 depth from the missing edge to the center of the circle measured with a femoral gauge, PAM3 calculated Percentage area missing from R3 and D3 using the function "q" (Appendix), AVG average, SD standard deviation CONCLUSION: Using this simple method and the function provided, the eroded area of the anterior part of the glenoid in anterior glenohumeral instability can be calculated preoperatively using a 3D CT reconstruction of the glenoid with "subtraction" of the humeral head, obviating the need for sophisticated software to obtain this critical information for preoperative decision making.     

Comp Plan: A computer program to generate dose and radiobiological metrics from dose-volume histogram files

Treatment planning studies often require the calculation of a large number of dose and radiobiological metrics. To streamline these calculations, a computer program called Comp Plan was developed using MATLAB. Comp Plan calculates common metrics, including equivalent uniform dose, tumor control probability, and normal tissue complication probability from dose-volume histogram data. The dose and radiobiological metrics can be calculated for the original data or for an adjusted fraction size using the linear quadratic model. A homogeneous boost dose can be added to a given structure if desired. The final output is written to an Excel file in a format convenient for further statistical analysis. Comp Plan was verified by independent calculations. A lung treatment planning study comparing 45 plans for 7 structures using up to 6 metrics for each structure was successfully analyzed within approximately 5 minutes with Comp Plan. The code is freely available from the authors on request.     

Concurrent validity of the PAM accelerometer relative to the MTI Actigraph using oxygen consumption as a reference

The purpose of this study was to examine the concurrent validity of the Personal Activity Monitor (PAM) accelerometer relative to the Actigraph accelerometer using oxygen consumption as a reference, and to assess the test–retest reliability of the PAM. Thirty-two fit, normal weight adults (aged 21–54) performed two activities, treadmill walking and stair walking, while wearing the PAM, the Actigraph and the Cosmed K4b². Correlation coefficients and agreement in absolute energy expenditure (EE) levels between PAM, Actigraph and Cosmed were calculated. The test–retest reliability was examined among 296 PAM's using a laboratory shaker. Intraclass correlation coefficients (ICC) and coefficient of variation (CV) were determined. Correlations for treadmill walking and stair walking, respectively, were r ²=0.95 and r ²=0.65 for PAM with Actigraph, r ²=0.82 and r ²=0.93 for PAM with VO₂ and r ²=0.64 and 0.74 for Actigraph with VO₂. Both the PAM and Actigraph underestimated EE during treadmill and stair walking by a substantial amount. The test–retest reliability of the PAM was high [ICC=0.80; 95% confidence interval (CI) (0.28;0.92) and intra-CV=1.5%]. The PAM and Actigraph accelerometer are comparable in assessing bodily movement during treadmill and stair walking. The PAM is a valid device to rank subjects in EE and can be useful in collecting objective data to monitor habitual physical activity.     

CT图像三维重建在复杂颈椎骨折的诊断和治疗中的应用价值

目的 直观立体地显示复杂颈椎骨折的图像,探讨螺旋CT医学图像三维重建在复杂颈椎骨折诊断中的价值及其对手术的指导意义。方法 对113例颈椎骨折采用螺旋CT进行薄层扫描和三维重建进行诊断。CT扫描全部采用Siemens SOMATOM Sensation 16型多排高速螺旋CT机,1.0mm层厚。扫描所得断层资料,通过网络传送至计算机工作站处理。采用Window.NT 3.51平台上Insight三维重建软件进行三维重建。结果 三维CT图像能够围绕X轴和Z轴任意旋转、切割,以从不同角度观察,能够清晰显示复杂的颈椎骨折和狭窄椎管的解剖形态特点。结论 三维CT重建在颈椎骨折方面具有较大的临床应用价值,有助于提高颈椎骨折手术的安全性和精确性,并对患者预后的估计提供帮助。     

High resolution computed tomographic features of pulmonary alveolar microlithiasis

BACKGROUND: Pulmonary alveolar microlithiasis (PAM) is a rare, chronic lung disease with unknown etiology and with a nonuniform clinical course. Nonuniformity of clinical course might be related to the degree of pulmonary parenchymal alterations, which can be revealed with high resolution computed tomography (HRCT). However, HRCT findings of PAM were not fully described in the current literature. AIM: The aim of this study was to interpret and to contribute to describe HRCT findings of PAM and to investigate a correlation between profusion of micro nodules (MN) and pulmonary parenchymal alterations in patients with PAM. MATERIAL AND METHODS: Ten male patients with PAM (mean age: 22+/-3.2) were included into the study. HRCT images were assessed for patterns, distribution, and profusion of pulmonary abnormalities. Dividing the lungs into three zones, profusion of abnormalities was assessed. A profusion score (1-4) was given and the scores of each zone were then summed to obtain a global profusion score for HRCT ranging from 0 to 12. Also a parenchymal alteration score (PAS) was defined with respect to profusion of abnormalities. Chest X-rays were also scored. RESULTS: All of ten patients with PAM had findings of interstitial lung disease in varying degrees on their HRCTs. HRCT findings of patients with PAM were as following: MN, parenchymal bands (PB), ground glass opacity (GGO) and, sub pleural interstitial thickening (SPIT) in 10 patients; interlobular septal thickening (ILST), in 9 patients; paraseptal emphysema (PSA) in 8 patients; centrilobular emphysema (CLA) in 7 patients; bronchiectasis (BE), confluent micro nodules (CMN) in 6 patients; peri bronchovascular interstitial thickening (PBIT) in 5 patients; panacinar emphysema (PANAA) in 3 patients; pleural calcification (PC) in 2 patients. A significant correlation between MN scores and PAS (r=0.68, p=0.031, MN scores and GGO scores (r=0.69, p=0.027) and, MN scores and CLA scores (r=0.67, p=0.034) was detected. We also found significant correlations between HRCT scores and results of pulmonary function tests (PFTs), HRCT scores and chest X-ray score (CXRS) and, CXRS and results of PFTs. CONCLUSION: We conclude that patients with PAM may have all findings of interstitial lung disease in varying degrees as well as MNs on their HRCTs. More importantly, this study suggests a proportional relationship between profusion of MNs and parenchymal alterations in patients with PAM. This study also suggests that the degree of parenchymal alterations closely related with the degree of pulmonary function loss in patients with PAM.