放射性同位素示踪技术在药物研发过程中的应用

药物的吸收、分布、代谢和排泄过程决定了药物分子在体内的过程和命运。作为常规生物样本检测技术的有效补充,放射性同位素标记示踪技术如今也被广泛应用于药物发现和开发过程中的各个阶段。特别是其高灵敏性、适用范围广的特点使其具有不可比拟的优势。通过对近年来放射性标记技术在药物评价领域中的应用进行了归纳和梳理,为药物研发相关领域研究人员提供可借鉴的参考。     

Extensor tendon ruptures in rheumatoid wrists

European Journal of Orthopaedic Surgery & Traumatology - Rheumatoid arthritis is a chronic inflammatory disease. The associated involvement of hands and tendons is over 90% and impairs overall...     

鼻中隔矫正术对变应性鼻炎伴鼻中隔偏曲患者生活质量的影响

目的评价鼻中隔偏曲矫正术对持续性变应性鼻炎（allergicrhinitis,AR）伴鼻中隔偏曲患者症状和生活质量的影响。方法应用症状视觉模拟评分量表（Visual Analogue Scale,VAs）和鼻结膜炎生存质量量表（Rhinocon junctivitis Quality of Life Questionnaire,RQI。Q）对62例持续性变应性鼻炎伴鼻中隔偏曲患者行鼻中隔偏曲术前、术后1个月、术后6个月临床症状和生活质量进行研究。结果鼻中隔偏曲矫正术后1个月、6个月患者症状、生活质量较术前均得到改善。术后1个月、6个月RQI．Q量表中各个维度的得分较术前明显降低,差异有统计学意义（P〈0．05）;术后6个月除总评分外,其余各维度与术后1个月比较,差异无统计学意义（P〉0．05）。VAS量表显示：术后患者症状较术前均有不同程度的改善,但改善最明显的为鼻塞,其次为打喷嚏。结论变应性鼻炎伴鼻中隔偏曲患者的生活质量降低,鼻中隔偏曲矫正术能明显的改善患者症状同时能提高患者的生活质量。     

DNA strand breaks measured within 100 milliseconds of irradiation of Escherichia coli by 4 MeV electrons.

A method was developed in which E. coli cells were irradiated with four MeV electrons and transferred to alkaline detergent within a fraction of a second. This technique minimizes the amount of repair of radiation damage before analysis without the necessity of using physical or chemical treatments to inhibit repair and alter the physiological condition of the cells. The yield of DNA strans breaks formed in covalent circular superhelical lambda DNA molecules superinfecting E. coli lysogens was about 4-fold greater when the cells were irradiated in oxygen than when they were irradiated under nitrogen anoxia. The same yields were obtained in phosphate buffer at 3 degrees and 22 degrees as well as in growth medium at 37 degrees, and the yields were not altered by the polA1 mutation. When E. coli lysogenic cells superinfected with lambda were irradiated with doses sufficient to introduce at least seven breaks in the phage DNA, the chromosomal DNA and the superinfecting phage DNA sedimented similarly in alkaline sucrose gradients, indicating that both DNAs were broken to a similar extent during irradiation. However, the yield of breaks calculated for chromosomal DNA in similar experiments was greater than the yield calculated from the first break introduced into covalent circular lambda DNA molecules. These apparently contradictory results are explicable either if the initial break in a superhelical molecule occurs with an efficiency different from that for subsequent breaks, or if the pulsed electron radiation produces a high proportion of double-strand breaks.     

Identification of the uvrC gene product.

We have constructed a multicopy plasmid that carries the uvrC gene of Escherichia coli. By inserting the transposon Tn1000 (previously designated gamma delta) into this plasmid, we obtained many derivatives that fail to complement uvrC34. The proteins synthesized by the original plasmid and the uvrC::Tn1000 derivatives were labeled in maxicells and analyzed on gels, demonstrating that a protein of Mr 70,000 encoded by the original uvrC+ plasmid was absent from the mutated noncomplementing derivatives; this protein is presumed to be the uvrC gene product. We found that this protein of Mr 70,000 binds to DNA and have partially purified the uvrC protein by DNA-cellulose chromatography. Because some of the uvrC::Tn1000 derivatives produce truncated polypeptides, the orientation of expression and the location of the promoter were determined by correlating the sizes of the truncated polypeptides with the sites of insertion of Tn1000.     

Sequences of the recA gene and protein.

We have determined the nucleotide sequence of the recA gene of Escherichia coli; this permits the formulation of the primary structure for the recA protein. This structure is consistent with the amino acid composition of the tryptic peptides obtained from the recA protein. The coding region of the recA gene has 1059 base pairs, which specify 352 amino acids. The recA protein has alanine and phenylalanine as its NH2- and COOH-terminal amino acids, respectively, and has the following amino acid composition: Cys3 Asp20 Asn15 Met9 Thr17 Ser20 Glu30 Gln13 Pro10 Gly35 Ala38 Val22 Ile27 Leu31 Tyr7 Phe10 His2Lys27 Trp2 Arg14. Of the three cysteine residues, only two can be alkylated under reducing and denaturing conditions. The molecular weight of the recA polypeptide is 37,842.     

藏族初中生心理健康状况与应对方式的关系研究

目的 了解应对方式对藏族初中生心理健康状况的影响。方法 采用自编的一般资料,中学生心理健康评定量表、简易应对方式问卷对786名藏族初中生进行问卷调查。结果 分层回归分析显示,第一层人口变量中上学方式、年级、家庭人均月收入、是否留守、学习成绩进入藏族初中生心理健康状况的回归方程(F=8.526,P=0.000),控制人口变量后,应对方式能独立解释心理健康状况21.70%的方差变异。结论 住校、初一、留守、学习成绩差、家庭收入低的藏族初中生心理健康状况差;管理者加强应对技巧的培训,能改善藏族初中生的心理健康状况。     

Cerebral hemodynamic and ventilatory responses to hypoxia,hypercapnia, and hypocapnia during 5 days at 4,350?m

This study investigated the changes in cerebral near-infrared spectroscopy (NIRS) signals, cerebrovascular and ventilatory responses to hypoxia and CO₂ during altitude exposure. At sea level (SL), after 24 hours and 5 days at 4,350 m, 11 healthy subjects were exposed to normoxia, isocapnic hypoxia, hypercapnia, and hypocapnia. The following parameters were measured: prefrontal tissue oxygenation index (TOI), oxy- (HbO₂), deoxy- and total hemoglobin (HbTot) concentrations with NIRS, blood velocity in the middle cerebral artery (MCAv) with transcranial Doppler and ventilation. Smaller prefrontal deoxygenation and larger ΔHbTot in response to hypoxia were observed at altitude compared with SL (day 5: ΔHbO₂−0.6±1.1 versus −1.8±1.3 μmol/cmper mm Hg and ΔHbTot 1.4±1.3 versus 0.7±1.1 μmol/cm per mm Hg). The hypoxic MCAv and ventilatory responses were enhanced at altitude. Prefrontal oxygenation increased less in response to hypercapnia at altitude compared with SL (day 5: ΔTOI 0.3±0.2 versus 0.5±0.3% mm Hg). The hypercapnic MCAv and ventilatory responses were decreased and increased, respectively, at altitude. Hemodynamic responses to hypocapnia did not change at altitude. Short-term altitude exposure improves cerebral oxygenation in response to hypoxia but decreases it during hypercapnia. Although these changes may be relevant for conditions such as exercise or sleep at altitude, they were not associated with symptoms of acute mountain sickness.