Synthesis and biological activities of fluorescent acridine-containing HIV-1 nucleocapsid proteins for investigation of nucleic acid-NCp7 interactions

Specific interactions between the 72-amino acid nucleocapsid protein NCp7 of the human immunodeficiency virus, type 1 and the genomic RNA are essential for virus replication. Studies on the mechanism of action of NCp7 require a direct visualization of its complexes with nucleic acids and the determination of binding affinities. To facilitate these investigations, fluorescent NCp7 derivatives were developed by introduction in the NCp7 sequence of a non-natural amino acid, (S)-β-(9-acridinyl)alanine (Aca) obtained by a chiral synthetic method. Three fluorescent NCp7 derivatives were obtained by introducing this amino acid at different positions. As shown by NMR, the three-dimensional structure of NCp7 is not altered by introduction of Aca. The fluorescent peptides were found to be as potent as their precursors in interacting with nucleic acids and in promoting HIV-1 genomic RNA dimerization. Moreover, because of their fluorescent properties, these NCp7s can be used at submicromolar concentrations to directly visualize and quantify protein-nucleic acid interactions in solution or after gel electrophoresis. This could facilitate the development of new antiviral agents aimed at inhibiting the functions of NCp7 and studies on the intracellular traffic of NCp7 within the preintegration complex.     

The substance specificity of psychosocial correlates of alcohol, tobacco, coffee and drug use by Czech women

The paper reports results of an analysis based on face-to-face interviews with two samples of Prague women aged 20-49: (1) a probabilistic sample (h = 718) of the Prague female population; and (2) a sample of 152 inpatients treated for substance dependence/abuse. Of the inpatients, 79% were diagnosed as alcohol dependent only, 15% as both alcohol dependent and drug dependent/abusers, 6% as drug dependent only. With very few exceptions, those with drug problems among the inpatients abused analgesics, hypnotics, or anxiolytics. With data obtained from the general population sample, two-stage hierarchical logistic regression was run with each of the eleven differently defined substance uses as dependent variables. Four demographic variables were entered as predictors into the regression equations in the first stage. From the seven potential risk factors of substance use statistically significant predictors were entered stepwise in stage two. The major result of the study is the specificity of the pattern of predictors related to each of the eleven considered substance uses. It is also found that in the general population the use of a particular substance is generally uncorrelated with the use of other substances. Alcohol use (even heavy alcohol use) has no relation to smoking, to the use of analgesics, hypnotics, anxiolytics-and is connected with a specific pattern of predictors.     

Polymorphism of the thiopurine S-methyltransferase gene in African- Americans

The molecular basis for the genetic polymorphism of thiopurine S - methyltransferase (TPMT) has been estab-lished for Caucasians, but it remains to be elucidated in African populations. In the current study, we determined TPMT genotypes in a population of 248 African-Americans and compared it with allele frequencies in 282 Caucasian Americans. TPMT genotype was determined in all individuals with TPMT activity indicative of a heterozygous genotype (</=10.1 U/ml pRBC, n = 23African- Americans, n = 21 Caucasians) and a control group with TPMT activity indicative of a homozygous wild-type genotype (>10.2 U/ml pRBC, n = 23 African-Americans, n = 21 Caucasians). No mutant alleles were found in the high activity control groups. The overall mutant allele frequencies were similar in African-Americans and Caucasians (4.6 and 3.7% of alleles, respectively). However, while TPMT*3C was the most prevalent mutant allele in African-Americans (52.2% of mutant alleles), it represented only 4.8% of mutant alleles in Caucasians ( P < 0.001). In contrast, TPMT*3A and TPMT*2 were less common in African-Americans (17.4 and 8.7% of mutant alleles), whereas TPMT*3A was the most prevalent mutant allele in Caucasians (85.7% of mutant alleles). A novel allele ( TPMT*8 ), containing a single nucleotide transition (G644A), leading to an amino acid change at codon 215 (Arg-->His), was found in one African-American with intermediate activity. These data indicate that the same TPMT mutant alleles are found in American black and white populations, but that the predominant mutant alleles differ in these two ethnic groups.      

硝苯吡啶与格列本脲相互作用对正常大鼠和高血糖大鼠血糖水平的影响

目的 :研究硝苯吡啶以及硝苯吡啶与格列本脲合用对空腹大鼠和肾上腺素诱发高血糖大鼠血糖水平的影响。方法 :本实验采用葡萄糖氧化酶法测定血糖含量。结果 :硝苯吡啶 2 .5mg/kgig使空腹大鼠血糖水平显著升高(P <0 .0 1 ) ,并加重肾上腺素诱发的高血糖反应。而硝苯吡啶与降糖药格列本脲 0 .9mg/kg合用时不影响空腹大鼠的血糖水平 ,硝苯吡啶对肾上腺素诱发高血糖大鼠灌胃格列本脲后的降血糖作用亦无明显影响。结论 :尽管硝苯吡啶对空腹大鼠以及肾上腺素诱发高血糖大鼠有显著升高血糖的作用 ,但对格列本脲的降血糖作用无明显不良影响     

HPLC法同时测定注射用甲氧异腈中FSA和MIBI的含量

目的 :采用RP HPLC法同时测定了注射用甲氧异腈中两种主要成份二氧硫脲 (FSA)和四 (甲氧基异丁基异腈 )络铜 (I)氟硼酸盐 (MIBI)的含量。方法 :以甲醇、磷酸二氢铵 ( 80∶2 0 )为流动相 ,检测波长 2 1 5nm ,HPLC法测定含量。结果 :试验表明 ,FSA和MIBI在 2 5～ 1 2 5μg/ml,50～ 2 50 μg/ml范围内呈良好的线性关系 ,回归方程分别为Y =0 .2 3 0 .0 2X(r =0 .994 6) ,Y =-2 .1 9 0 .0 3X(r =0 .9998) ,相对标准偏差分别为 1 .2 5%和 0 .4 2 %。结论 :该方法简便、准确、可靠     

动脉功能不全与溃疡的诊断与治疗选择

多种全身疾病可以导致下肢溃疡,其中最常见的原因是诸如周围动脉和静脉的血管疾病。周围动脉疾病是一种进展缓慢的、隐匿的疾病进程,在美国大约800万~1 200万人受累于此病,而且每年的发病率还在不断增长。有20%的65岁以上的美国人患有周围动脉疾病,其中只有25%的人接受治疗。据估计,1 050万该病患者有症状,而另外1 650万的该病患者则无症状。有研究结果报道下肢溃疡的发病率为0·12%~1·8%。由于病人及初级治疗提供者不清楚周围动脉疾病的早期表现,并且几乎没有治疗方面的知识,因此常常不能做出正确诊断。动脉溃疡的病理生理学动脉血供不足…     

Pentalinon andrieuxii Root Extract is Effective in the Topical Treatment of Cutaneous Leishmaniasis Caused by Leishmania mexicana

Cutaneous leishmaniasis (CL) manifests as localized skin lesions, which lead to significant tissue destruction and disfigurement. In the Yucatan Peninsula, Mayan traditional healers use Pentalinon andrieuxii Muell.‐Arg. (Apocynaceae) roots for the topical treatment of CL. Here, we studied the effect of P. andrieuxii root hexane extract (PARE) on the parasites and host cells in vitro and examined its efficacy in the topical treatment of CL caused by Leishmania mexicana. PARE exhibited potent antiparasitic activity in vitro against promastigotes as well as amastigotes residing in macrophages. Electron microscopy of PARE‐treated parasites revealed direct membrane damage. PARE also activated nuclear factor kappaB and enhanced interferon‐γ receptor and MHC class II expression and TNF‐α production in macrophages. In addition, PARE induced production of the Th1 promoting cytokine IL‐12 in dendritic cells as well as enhanced expression of the co‐stimulatory molecules CD40, CD80, and CD86. In vivo studies showed that L. mexicana‐infected mice treated by topical application of PARE resulted in the significant reduction in lesion size and parasite burden compared to controls. These findings indicate that PARE could be used as an alternative therapy for the topical treatment of CL. Copyright © 2013 John Wiley & Sons, Ltd.     

卡马西平片质量分析评价

卡马西平 (Ｃａｒｂａｍａｚｅｐｉｎｅ ,简称ＣＢＺ)为一种重要的抗癫痫药物 ,自发现以来一直广泛应用于临床 ,近年来越来越多的临床医师和服药病人反映 ,服用不同生产厂家 ,甚至同一厂家不同批号的卡马西平片后出现不同治疗效果。为此 ,我们分析了广东地区医药市场使用的部分卡马西平片 ,测定了其质量并作了评价。1　仪器与试药ＵＶ - 2 6 5ＦＷ型紫外分光光度计 (日本岛津 ) ;ＲＣＤ - 6型溶出度仪 ;78Ｘ2型片剂四用测定仪 (上海黄海药检仪器厂 ) ;电子天平 (Ｓａｒｔｏｒｉｏｕｓ ,ＧＡ15 0 0Ｄ ,0 .1ｍｇ ,德国托普仪器有限公司 )。超…     

Epidepride的合成

目的：研究Epidepride的化学合成方法。方法：以3－甲氧基水杨酸为原料,经五步反应合成Epidepride。结果：得到的样品经IR,NMR,MS等波谱分析及元素分析证明该化合物为Epidepride,总收率为43％。结论：该合成方法简单,收率稳定,反应条件温和。