交沙霉素在中国汉族、维吾尔族及哈萨克族中的药代动力学比较

交沙霉素在中国汉族、维吾尔族及哈萨克族中的药代动力学比较李国昌陈春雁杨明义（新疆石河子医学院第一附属医院药剂科，石河子８３２００８；石河子农学院医院，石河子８３２００３）为探讨交沙霉素（ｊｏｓａｍｙｃｉｎ）在不同民族正常人体内过程，我们用相同的受...     

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.     

Methodological issues associated with clinical trials in epilepsy

Introduction: despite methodological advances in epilepsy clinical trials, the proportion of patients reaching seizure-freedom has not substantially changed over the years. We review the main methodological limitations of current trials, the possible strategies to overcome these limits, and the issues that need to be addressed in next future.

Area covered: references were identified by PubMed search until March 2017 and unpublished literature was searched on ClinicalTrials.gov. Add-on trials mainly involve refractory epilepsy subjects, reducing overall response to the investigational drug. The inclusion of subjects with earlier disease from less developed countries has partially allowed overcoming this limitation, but has introduced more random variability of results. Monotherapy trials rise methodological, economical, and ethical concerns with different regulatory requirements in European Union and in the United States of America. Newer trial designs, such as futility trials or ‘time-to-event’ design, have been implemented. Moreover, both add-on and monotherapy trials results might be affected by patient’s ability to recognize and record seizures, and by randomness of seizures occurrence over time. Possible strategies to achieve more reliable outcomes are detailed.

Expert commentary: clinical trial methodology needs to be optimized to better address regulatory agencies requirements and to encounter both patients’ and clinicians’ needs.     

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