Synthesis of two nitro analogs of tranylcypromine: Relations of aromatic substitution of nitro groups to MAO-Inhibitory activity

Two new nitro analogs of tranylcypromine, (E)-2-(p-nitrophenyl)cyclopropylamine ((E)-p-NTCP) and (E)-2-(m-nitrophenyl)cyclopropylamine ((E)-m-NTCP) were synthesized in order to examine the effect of aromatic nitro substitution on the MAO-inhibitory activity of 2-phenylcyclopropylamines. The compounds were obtained by treatingt-butyl (E)-2-(p-nitrophenyl) cyclopropanecarbamate andt-butyl (E)-2-(m-nitrophenyl)cyclopropanecarbamate withp-toluenesulfonic acid in CH₃CN. Inhibitions of rat brain mitochondrial MAO-A and B by the compounds were examined using serotonin and benzylamine as the substrate at bothin vitro andex vivo levels. It was found fromin vitro measurements that(E)-p-NTCP at 6.0×10^?5M elicited merely 22.5% inhibition against MAO-B without any effect on MAO-A. In contrast,(E)-m-NTCP showed fair degrees of inhibitions of MAO-A and B with IC₅₀ values, 2.5×10^?7M and 1.4×10^?6M, respectively. It was also noted from(E)-m-NTCP thatm-nitro substitution caused a shift of selectivity of the inhibition toward MAO-A. According toex vivo measurements at 1.5, 3, 6, and 12 hr following the administration of a dose of 0.015 mmol/kg, i.p. to the rats, the inhibition percents of MAO-A by(E)-m-NTCP were 58.6, 63.7 63.6, and 46.6%, slightly lower than those observed by tranylcypromine. Whereas,(E)-p-NTCP at the same dose level did not show significant inhibitions against both MAO-A and MAO-B. Possible reasons for the difference in potencies between(E)-m-NTCP and(E)-p-NTCP were sought in relation to differing electron withdrawing effects ofm-andp-substituents which will influence electron density of the side chain amino functions and the partitions.     

443例胃癌根治术后发生肺部并发症的危险因素

目的 探讨胃癌根治术术后肺部并发症(PPCs)的相关危险因素,为PPCs的个体化防治提供相应的对策。 方法 回顾性分析2019年1月至2021年3月兰州大学第二医院普通外科443例胃癌患者的临床资料,统计患者的临床病理特征,采用二分类Logistic回归分析胃癌根治术PPCs的危险因素。 结果 443例胃癌根治术PPCs的发生率为18.1%(80/443),其中肺部感染的发生率为12.4%(55/443),胸腔积液的发生率为11.7%(52/443),发生PPCs较未发生PPCs住院时间延长。Logistic回归分析显示,年龄≥60岁(OR=0.424、95%CI: 0.241~0.746)、糖尿病史(OR=0.318、95%CI: 0.146~0.693)、每分钟最大通气量(MVV)(%)<85%(OR=0.509、95%CI: 0.297~0.874)、术中失血量≥200 mL(OR=0.496、95%CI: 0.276~0.797)和术后吻合口并发症(OR=4.038、95%CI: 1.250~13.049)是胃癌根治术发生PPCs的独立危险因素。 结论 对于年龄≥60岁、糖尿病史、MVV(%)<85%、术中失血量≥200 mL、术后吻合口并发症的胃癌患者,应注意预防PPCs的发生。     

Direct visualization and cellular localization of D1 and D2 dopamine receptors in rat forebrain by use of fluorescent ligands.

The regional and cellular localization of the two subtypes of dopamine receptors, D1 and D2, have been ascertained in rat forebrain by use of fluorescent dopaminergic antagonist ligands. (R,S)-5-(4'-aminophenyl)-8-chloro-2,3,4,5-tetrahydro-3- methyl-[1H]-3-benzazepin-7-ol, the 4'-amino derivative of the high-affinity D1-specific antagonist SCH 23390, and the D2 selective antagonist N-(p-aminophenethyl)spiperone were chemically derivatized using the fluorescent compound tetramethylrhodamine. The modification of these antagonist ligands has allowed the specific, cellular resolution of the D1 and D2 receptor binding sites in intact, highly organized regions of forebrain slices in a very rapid experimental time frame. The regional localization of receptors labeled by the fluorescent probes is in agreement with previous receptor autoradiography studies. Moreover, the specific cellular binding patterns for both receptors can now be compared and contrasted to one another in the same tissue by using these fluorescent ligands. D1 receptor sites are most evident within the striatum and exhibit regions of intense "patch" fluorescence corresponding to receptor reactivity in cells and their processes. The distribution of D1 receptor binding is highly analogous to the pattern of dopamine terminal histofluorescence in the caudate nucleus. D2 receptor sites are less prevalent overall and may be localized to a subpopulation of the D1 fluorescent neurons in the caudate nucleus and nucleus accumbens regions.     

Comparison of the biomechanical effect of posterior condylar offset and kinematics between posterior cruciate-retaining and posterior-stabilized total knee arthroplasty

Background

The effect of the changes in the femoral posterior condylar offset (PCO) on anterior–posterior (AP) translation and internal–external (IE) rotation in cruciate-retaining (CR) and posterior-stabilized (PS) total knee arthroplasty (TKA) remains unknown. The purpose of this study was to compare the kinematics in CR and PS TKA with respect to the difference in prosthetic design and PCO change through a computational simulation.

明胶-聚乳酸载药纳米微球的制备及其体外释药研究

采用复合乳液—溶剂挥发法制得明胶—聚乳酸载五氟脲嘧啶(5—Fu)微球，以混合型乳化剂Tween—80：Span—80＝5：1—作为初乳乳化剂，O—羧甲基壳聚糖作为复乳乳化剂，考察了明胶—聚乳酸载药微球的制备条件对微球的成球性、药物包封率及体外释药的影响。结果表明乳化剂的选择、内部水相药物浓度和PLA分子量等均对载药微球的结构与性能产生影响，经优化条件得到了成球性和体外释放都比较好的载药微球。     

门静脉的体表定位及其临床意义

目的：为超声波检查门静脉或经皮经肝门静脉穿刺提供解剖学基础。方法：在４０例成人尸体标本上观测了门静脉的行程及其分叉位置的体表投影。结果：门静脉肝外段与身体的垂线呈约４０°角；门静脉分叉位置在经右半胸宽中点的垂线与右锁骨中线上肝高中点的水平线的交点附近；门静脉右支分为前、后支的位置在剑突尖平面下方约２ｃｍ，右锁骨中线上肝高的中点附近；门静脉左支分出第１外侧支的位置在剑突尖稍下方的右侧约２ｃｍ。结论：在右腋中线剑突尖平面下方约２ｃｍ经皮经肝穿刺至锁骨中线，导管即可进入门静脉右支内     

Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients

Classical citrullinemia (CTLN1), a rare autosomal recessive disorder, is caused by mutations of the argininosuccinate synthetase (ASS) gene, localized on chromosome 9q34.1. ASS functions as a rate-limiting enzyme in the urea cycle. Previously, we identified 32 mutations in the ASS gene of CTLN1 patients mainly in Japan and the United States, and to date 34 different mutations have been described in 50 families worldwide. In the present study, we report ASS mutations detected in 35 additional CTLN1 families from 11 countries. By analyzing the entire coding sequence and the intron-exon boundaries of the ASS gene using RT-PCR and/or genomic DNA-PCR, we have identified 16 novel mutations (two different 1-bp deletions, a 67-bp insertion, and 13 missense) and have detected 12 known mutations. Altogether, 50 different mutations (seven deletion, three splice site, one duplication, two nonsense, and 37 missense) in 85 CTLN1 families were identified. On the basis of primary sequence comparisons with the crystal structure of E. coli ASS protein, it may be concluded that any of the 37 missense mutations found at 30 different positions led to structural and functional impairments of the human ASS protein. It has been found that three mutations are particularly frequent: IVS6-2A>G in 23 families (Japan: 20 and Korea: three), G390R in 18 families (Turkey: six, U.S.: five, Spain: three, Israel: one, Austria: one, Canada: one, and Bolivia: one), and R304W in 10 families (Japan: nine and Turkey: one). Most mutations of the ASS gene are "private" and are distributed throughout the gene, except for exons 5 and 12-14. It seems that the clinical course of the patients with truncated mutations or the G390R mutation is early-onset/severe. The phenotype of the patients with certain missense mutations (G362V or W179R) is more late-onset/mild. Eight patients with R86H, A118T, R265H, or K310R mutations were adult/late-onset and four of them showed severe symptoms during pregnancy or postpartum. However, it is still difficult to prove the genotype-phenotype correlation, because many patients were compound heterozygotes (with two different mutations), lived in different environments at the time of diagnosis, and/or had several treatment regimes or various knowledge of the disease.     

An azurocidin-like protein is induced in Trichoplusia ni larval gut cells after bacterial challenge

Trichoplusia ni immune genes up-regulated in response to bacterial infection have been isolated using differential display polymerase chain reaction. Here we report the cloning and characterisation of a gut-specific immune gene encoding an azurocidin-like protein. The deduced protein is 317 amino acid residues long with a hydrophobic C-terminus and a predicted 17-residue signal peptide. The mature T. ni protein shows 30% identity to human azurocidin, an antibacterial protein. Like azurocidin, the T. ni protein contains two amino acid substitutions in the active site triad normally present in serine proteases. The T. ni protein was synthesised with a six-histidine C-terminal extension using the baculovirus expression system. Sequencing of the recombinant azurocidin-like protein confirmed the predicted cleavage of the signal peptide. Northern blots show that T. ni azurocidin-like protein is expressed solely in the larval gut and that expression is up-regulated by injecting or feeding bacteria. Expression reaches its highest level at 10 h after bacteria injection.