一类新型取代苯甲基雌甾咪唑Weng盐的合成

用雌二醇经溴乙基化、咪唑乙基化，季铵化和水解反应，合成一类新型的取代苯甲基雌甾咪唑Ｗｅｎｇ盐。     

含硫咪唑及其衍生物的合成

1.合成了8-(β-氨乙基巯基)及8-(β-胍乙基巯基)咖啡碱与它们的类似物8-(β-巯乙基氨基)及8-(β-S-异硫脲基乙基氨基)咖啡碱。2.由巯基化合物与β-溴乙胺溴氢酸盐直接反应,制备了具有β-氨乙基巯基的苯并咪唑、甲基咪唑、苯并咪唑及咪唑啉等衍生物。     

离子液体促进氟罗沙星的合成

2,3,4-三氟苯胺经与EMME缩合、环合、氟乙基化、与N-甲基哌嗪缩合和水解反应制得氟罗沙星,前4步反应可被离子溶剂1-丁基-3-甲基咪唑六氟磷酸盐促进,如环合反应温度由300℃降至200℃,总收率61%.     

新咪唑啉化合物的抗微生物作用

业已报道,具有抗静电、抑菌及防腐性质的咪唑啉盐类是一组阳离子界面活性剂。本文报道由1-乙基-2-烷基-3-(烷氧甲基)-及1-乙基-2-烷基-3-(烷硫甲基)氯化咪唑啉合成的一组新化合物的合成方法及其抗微生物作用。一、合成1-乙基-2-烷基-3-(烷氧甲基)-及1-乙     

舍吲哚的合成

1-(2-氯乙基)-2-咪唑啉酮和哌啶酮盐酸盐缩合得1-[2-(2-氧代咪唑啉)乙基]哌啶-4-酮,再和1-(4-氟苯基)-5-氯吲哚(3)缩合得1-[2-[4-[5-氯-1-(4-氟苯基)-1H-吲哚-3-基]-1,2,3,6-四氢-1-吡啶]乙基]-2-咪唑啉酮,最后经还原制得舍吲哚,总收率约63%(以3计)。     

琥珀酸普卡必利的合成

对氨基水杨酸经甲酯化、乙酰化、氯代、溴代、溴乙基化、在锌粉作用下环合及水解反应得到4-氨基-5-氯-2,3-二氢苯并呋喃-7-羧酸(10).另用4-哌啶酮盐酸盐经甲氧丙基化及氨基化得到1-(3-甲氧基丙基)-4-哌啶胺(11).10与11在羰基二咪唑作用下经缩合、成盐得到便秘治疗药琥珀酸普卡必利,总收率约10％(以对氨基水杨酸计).     

唑类抗真菌药进展

近些年来,真菌感染的发病率呈上升趋势,日益引起人们的重视,抗真菌药的研究也成为热点之不,目前临床应用和研究得较多的是唑类抗真菌药,相继有几代产品问世,唑类抗真菌药的结构大致可分为４类,多苯甲基唑类,α－卤代苯乙基－β,Ｎ－咪唑乙基苄醚类,α－卤代苯乙基－α－环氧戊环唑类和α－卤代苯乙基三唑类,其代表药物分别为克霉唑、咪康唑、酮康唑和氟康唑。其基本药效基团为无取代唑环（咪唑或三唑）,间位Ｎ与真菌１４     

抗霉菌药1-[β-(对硝基苯氧基)-2,4-二氯苯乙基]咪唑硝酸盐的合成

合成抗霉菌药1-[β-(对-硝基苯氧基)-2,4-二氯苯乙基]咪唑时,制备2',4'-二氯-2-(1-咪唑基)苯乙酮(Ⅲ),用过量咪唑作缩合剂效果较好(过量咪唑可以回收)。α-(2,4-二氯苯基)咪唑-1-乙醇和对-硝基氯苯缩合时,使用极性和非极性溶剂并使用适当触媒优于用四氢呋喃。     

KD-042 硫康唑硝酸盐

1-[2-(2,4-二氯苯基)-2-(4-氯苯甲硫基)乙基]-1H-咪唑硝酸盐     

4-甲基-5-[(2-氨基乙基)硫甲基]咪唑制备的工艺改进

4-甲基-5-[(2-氨基乙基)硫甲基]咪唑二盐酸盐(1)是合成组胺 H_2-受体拮抗剂西咪替丁的重要中间体,一般是由4-甲基-5-羟甲基咪唑盐酸盐(2)和半胱胺盐酸盐(3)缩合而得,其工艺可分盐酸法、醋酸法、熔融     

联合治疗阻断乙型肝炎病毒垂直传播的研究

目的 探讨阻断乙型肝炎病毒（HBV）垂直传播的有效方案.方法 将387对夫妇（其必有一方HBV-DNA阳性）按要求分三组后再随机分组,用拉米夫定、乙肝免疫球蛋白（HBIG）干预.其HBV-DNA阳性婴儿共90例随机分三组,用HBIG、重组粒细胞-巨噬细胞集落刺激因子（Gm-CSF）、乙肝疫苗干预,用荧光探针定量聚合酶链反应（PCR）技术动态监测父、母、婴儿血HBV-DNA定量.结果 HBV-DNA阳性父/母用药后,各组HVB-DNA水平均较用药前明显下降,联合用药组与单独用药组比较,HBV-DNA水平下降幅度有统计学意义（P＜0.05）,单独用药组与联合用药组比较,其所生婴儿HBV-DNA阳性率明显增高（P＜0.05）;HBV-DNA阳性婴儿用药后,HBV-DNA下降水平,联合用药组与疫苗组差异有统计学意义（P＜0.05）;GM-CSF＋疫苗组与HBIG＋疫苗组比较HBV-DNA水平下降幅度差异有统计学意义（P＜0.05）.结论 HBV阳性父、母孕前用HBIG、拉米夫定,婴儿用乙肝疫苗、HBIG、Gm-CSF可有效阻断HBV垂直传播.     

Synthesis of phosphopeptides containing O-phosphoserine or O-phosphothreonine

Peptides containing phosphoserine or phosphothreonine were synthesized by solid phase methods. Phosphoserine and phosphothreonine were incorporated into peptides using Boc-diphenylphosphono esters of serine and threonine and standard DCC/HOBt coupling. The phenylphosphoesters were not removed when the peptides were cleaved from the resin by HF or by trifluoromethane sulfonic acid, but were subsequently removed by catalytic hydrogenation. Phosphopeptides were purified by HPLC and by Fe⁺³-Chelex chromatography and their identity verified by mass spectrometry. Two peptides, Leu-Arg-Arg-Ala-Ser(P)-Leu-Gly and Leu-Arg-Arg-Ala-Thr(P)-Leu-Gly, were prepared by both enzymatic and chemical methods and had identical properties.     

The rabbit rectococcygeus: A ganglion-free, parasympathetically innervated preparation

1 Isolated, desheathed preparations of the rabbit rectococcygeus muscle were relatively insensitive to spasmogens other than muscarinic drugs. Transmural stimulation with 1-50 pulses (0.2-0.4 ms at 10 Hz) elicited graded twitches which were abolished by tetrodotoxin and were therefore neurogenic; longer pulses sometimes triggered tetrodotoxin-resistant myogenic contractions.2 Twitches elicited by 0.2-0.4 ms pulses were due to post-ganglionic excitation because they were not reduced by hexamethonium, pentolinium or dimethyltubocurarine, or by ganglion-paralyzing concentrations of nicotine.3 The acetyl- and butyryl-cholinesterase activities of the rectococcygeus were determined manometrically and could be selectively inhibited by BW 284C51 (1:5-bis-(4-allyl-dimethylammonium-phenyl)-pentan-3-one dibromide) and iso-OMPA (tetramonoisopropylpyrophosphortetramide), respectively. Single-pulse twitches were greatly potentiated in amplitude and duration only when both cholinesterases were inhibited.4 The preparations could not be made to contract by nicotine (2.1-21 muM) even after cholinesterase inhibition, suggesting an absence of ganglion-cells; with nicotine (105-210 muM) small, atropine-susceptible responses were elicited, which were non-ganglionic because they were not reduced by tetrodotoxin.5 Rectococcygeus preparations that had been treated with physostigmine released acetylcholine into the bath fluid on electrical stimulation.6 The motor transmission was paralyzed by botulinum toxin (Type A) and abolished by atropine; the block of muscarinic receptors by atropine was effective against both endogenous and exogenous acetylcholine.7 Inhibitory adrenoceptors and scanty motor alpha-adrenoceptors were detected in the smooth muscle.8 Strong inhibitions of motor transmission and of rhythmic activity were produced by noradrenaline (but not by tyramine), by isoprenaline, and, after phentolamine, also by adrenaline and phenylephrine. These inhibitions were only slightly reduced by propranolol and rather more by pindolol.9 Experiments on preparations retaining their extrinsic nerve supply suggest an absence of ganglionic relays in the last 1-2 cm of the motor nerve pathway to this muscle.10 Some contrasting properties of the adjacent caudo-anal muscle, including the poor motor responses to transmural stimulation, are described.     

奥曲肽治疗急性胰腺炎临床研究

目的探讨奥曲肽注射液治疗急性胰腺炎的有效性和安全性。方法观察在综合治疗中早期使用奥曲肽注射液治疗急性胰腺炎患者64例效果,与非使用奥曲肽注射液治疗急性胰腺炎75例相比较,监测两组血清淀粉酶含量,同时比较两组并发症的发生率、并发症、住院时间。结果奥曲肽治疗组43例轻症急性胰腺炎(MAP)患者21例重症急性胰腺炎(SAP)患者血清淀粉酶治疗后48h、72h均明显降低,与非奥曲肽治疗组有显著性差异。奥曲肽治疗组平均住院时间为10.3d,非奥曲肽治疗组平均住院时间为15.8d,住院时间明显缩短。奥曲肽治疗组患者发生并发症21次,非奥曲肽治疗组发生并发症43次。结论奥曲肽注射液能有效降低血清和浆膜腔积液淀粉酶活性,能明显改善临床症状,缩短住院时间,减少并发症发生和病死率。     

反义FAK寡核苷酸抑制FAK-ERK1/2介导的平滑肌细胞迁移和粘附

目的研究FAK-ERK1/2信号通路在平滑肌细胞迁移和粘附中的作用及FAK反义寡核苷酸对其的调控作用。方法通过纤粘连蛋白(fibronectin,FN)诱导平滑肌细胞迁移和粘附,以免疫沉淀和Western blot方法检测粘着斑激酶(focal adhesion kinase,FAK)和细胞外调控激酶1/2(extracellular regulation kinase,ERK1/2)及其磷酸化的表达量。将FAK反义寡核苷酸(antisense oligodeoxynucleotides,ODNs)经脂质体转染细胞,观察转染后反义ODN对FAK和ERK磷酸化、细胞粘附和迁移的影响。结果FN在有效诱导平滑肌细胞迁移和粘附时FAK和ERK1/2也呈明显表达,FN 20 μg·mL^-1可使磷酸化处于较高表达量。脂质体可有效地介导ODNs转染。转染后FAK及ERK1/2磷酸化表达量明显减少。结论由活化的FAK和ERK1/2介导的信号转导促进了细胞外基质诱导的SMCs迁移和增殖,反义FAK ODNs可有效地对此进行抑制。     

抗人肝微粒体蛋白单克隆抗体细胞系的建立及鉴定

目的 初步建立抗人肝微粒体蛋白单克隆抗体规模化制备技术平台,为制备抗人细胞色素P450(CYP450)亚型蛋白的单克隆抗体奠定基础.方法 按常规方法进行细胞融合,以酶联免疫吸附测定法(ELISA)筛选杂交瘤,以ELISA、免疫组化(IH)、免疫印迹(Western Blot)、免疫沉淀(IP)对单克隆抗体加以鉴定.结果 融合后筛出杂交瘤,其分泌抗体类型为IgG1、IgG2a、IgG2b及IgM.免疫组化(IH)图片上,人肝细胞浆内均可见阳性颗粒.免疫沉淀(IP)和免疫印迹(WesternBlot)结果显示,所制备抗体与人肝微粒体蛋白有特异性结合.结论 筛选制备的单克隆抗体杂交瘤能分泌特异性较强的抗人肝微粒体蛋白单克隆抗体.     

超声在腹部平片阴性肠梗阻中的诊断价值

目的研究超声在腹部X线平片检查阴性的肠梗阻诊断中的价值。方法回顾我院2002～2011年经CT、手术证实为肠梗阻且腹部X平片为阴性而B超检查为阳性的36例患者的临床资料,对诊断结果进行分析。结果 36例患者经CT、手术证实梗阻原因中肠套叠18例,肠道肿瘤12例,粘连索带引起内疝3例,粪石梗阻1例,腹腔炎症引起肠梗阻2例。结论超声在肠梗阻诊断中具有一定的意义,可作为腹部X线平片诊断肠梗阻的补充检查。     

Autonomic receptors in isolated rainbow trout vasculature

Pre-gill arterial vessels (bulbus arteriosus and ventral aorta) from rainbow trout were easily excised, helically cut, and investigated; whereas, post-gill arterial and venous vessels were either too small or too enmeshed with connective tissue to permit study. Atropine shifted dose-response curves to acetylcholine in the bulbuss arteriousu and ventral aorta to the right. Responses to acetylcholine in the bulbus arteriosus were not antagonized by hexamethonium and tubocurarine. Physostigmine (10^?7 M) and diisopropylfluorphosphate (10^?4 M) did not alter responses to acetyl-choline in bulbus arteriosus. Contractions to pilocarpine were blocked by atropine. Contractile responses to epinephrine were antagonized by phentolamine, were potentiated by propranolol, and were not altered by cocaine. The potentiation of epinephrine by propranolol was greater in ventral aortic tissue located proximal to the heart. Relaxations of acetylcholine-induced contractions by isoproterenol were antagonized by propranolol. The results in this report indicate that the effects elicited by acetylcholine and pilocarpine in pre-gill arterial vasculature of rainbow trout were mediated by muscarinic receptors. This study also presents evidence for the presence of both α- and β-adrenoceptors in ventral aorta of rainbow trout.     

超声造影与彩色多普勒超声在产后胎盘植入诊断中的应用价值比较

目的 探讨产后胎盘植入及胎盘残留的超声造影和二维彩超的影像学特点,比较两种方法诊断产后胎盘植入的价值.方法 本院产科住院的临床疑诊产后或引产后胎盘植入的产妇43例,常规进行灰阶、彩色多普勒超声检查和超声造影检查.超声造影观察宫腔内异常回声团、子宫肌层、浆膜层的造影剂增强特点.并与病理或临床综合诊断结果比较,分析超声造影与灰阶结合彩色多普勒超声鉴别胎盘残留和植入的敏感性、特异性.结果 病理及临床诊断34例为胎盘植入,9例胎盘残留.超声造影正确诊断胎盘植入32例,正确诊断胎盘残留9例,2例胎盘植入误诊为胎盘残留.二维彩超诊断胎盘植入29例,诊断胎盘残留14例,其中25例胎盘植入与5例胎盘残留与临床病理诊断标准结果相符,胎盘植入误诊为胎盘残留9例.胎盘残留误诊为胎盘植入4例.超声造影及二维彩超诊断胎盘植入的敏感性分别是94.1％、73.5％,差异有统计学意义(P＜0.05);超声造影及彩色多普勒超声诊断胎盘植入的特异性分别为100.0％、55.5％,差异有统计学意义(P＜0.05).结论 超声造影在胎盘植入的诊断方面较彩色多普勒超声能够提供更准确的血流灌注信息,较后者更有优势.     

乳腺良恶性肿块的彩超鉴别诊断分析

目的：探讨彩色多普勒血流显像在乳腺良、恶性肿块鉴别诊断中的价值。方法：使用ATL HDI 3000型彩色多普勒超声诊断仪，以50 临床拟诊为乳腺占位性病变患者进行检查诊断，观察其二维图象表现及血流分布信息，血流显示所占肿块面积比例，血流动力学改变。结果：50例患者彩超诊断分别为：乳腺纤维瘤17例，乳腺癌10例，乳腺小叶增生结节15例，乳腺囊肿8例，被诊断的10例乳腺癌及部分纤维瘤患者经手术后病理证实验1例纤维瘤患者病理报告为乳腺癌早期改变外，全部符合彩超诊断，结论：彩超在乳腺良，恶性肿瘤的鉴别诊断中，有着重要的诊断价值。