赛赓啶对 KBV200细胞多药抗性的逆转作用

研究赛赓啶对KB_V200细胞多药抗性的逆转作用及逆转机制。在KB_V200细胞,采用MTT法,测出赛赓啶对长春新碱、阿霉素和鬼臼乙叉甙耐药的逆转系数分别为5.5,2.0和1.9,而对5-氟尿嘧啶、美法仑的细胞毒性作用无明显影响,表明赛赓啶为多药抗性逆转剂。荧光分光光度法测定表明,赛赓啶可使KB_V200细胞内阿霉素蓄积量增加。流式细胞荧光测定显示赛赓啶可增加罗丹明123的蓄积并减慢其外排。免疫细胞化学及狭缝杂交表明赛赓啶不影响KB_V200细胞的P-糖蛋白染色深度和 mdr1 RNA 表达水平。以上结果提示赛赓啶的多药抗性逆转机制是抑制P-糖蛋白泵的功能。     

Genomic Surveillance of SARS-CoV-2: Distribution of Clades in the Republic of Korea in 2020

Since a novel beta-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019, there has been a rapid global spread of the virus. Genomic surveillance was conducted on samples isolated from infected individuals to monitor the spread of genetic variants of SARS-CoV-2 in Korea. The Korea Disease Control and Prevention Agency performed whole genome sequencing of SARS-CoV-2 in Korea for 1 year (January 2020 to January 2021). A total of 2,488 SARS-CoV-2 cases were sequenced (including 648 cases from abroad). Initially, the prevalent clades of SARS-CoV-2 were the S and V clades, however, by March 2020, GH clade was the most dominant. Only international travelers were identified as having G or GR clades, and since the first variant 501Y.V1 was identified (from a traveler from the United Kingdom on December 22^nd, 2020), a total of 27 variants of 501Y.V1, 501Y.V2, and 484K.V2 have been classified (as of January 25^th, 2021). The results in this study indicated that quarantining of travelers entering Korea successfully prevented dissemination of the SARS-CoV-2 variants in Korea.     

CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs

The present study characterized Chinese hamster ovary cells overexpressing a human intestinal peptide transporter, CHO/hPEPT1 cells, as an in vitro model for peptidomimetic drugs. The kinetic parameters of Gly-Sar uptake were determined in three different cell culture systems such as untransfected CHO cells (CHO-K1), transfected CHO cells (CHO/hPEPT1) and Caco-2 cells. Vmax in CHO/hPEPT1 cells was approximately 3-fold higher than those in Caco-2 cells and CHO-K1 cells, while Km values were similar in all cases. The uptake of beta-lactam antibiotics in CHO/hPEPT1 cells was three to twelve fold higher than that in CHO-K1 cells, indicating that CHO/hPEPT1 cells significantly enhanced the peptide transport activity. However, amino acid drugs also exhibited high cellular uptake in both CHO-K1 and CHO/hPEPT1 cells due to the high background level of amino acid transporters. Thus, cellular uptake study in CHO/hPEPT1 cells is not sensitive enough to distinguish the peptidyl drugs from amino acid drugs. The potential of CHO/hPEPT1 cells as an in vitro model for peptidomimetic drugs was also examined through the inhibition study on Gly-Sar uptake. Peptidomimetic drugs such as beta-lactam antibiotics and enalapril significantly inhibited Gly-Sar uptake whereas the nonpeptidyl compounds, L-dopa and alpha-methyldopa, did not compete with Gly-Sar for cellular uptake within the therapeutic concentrations. In conclusion, the present study demonstrates the further characterization of CHO/hPEPT1 cells as an uptake model as well as inhibition study and suggests their utility as an alternative in vitro model for drug candidates targeting the hPEPT1 transporter.     

抗补体蛋白对大鼠局灶脑缺血损伤的作用

0　引言　近年来脑缺血损伤的早期炎症受到重视 .有学者观察到在人脑梗塞部位白细胞集聚 ,临床预后与梗塞部位的白细胞数量有关 ,白细胞多者预后差 [1 ] .还有文献描述了大鼠持续性脑缺血损伤中的多形核中性细胞反应的时间过程 ,收稿日期 :1999-0 3 -2 6;　修回日期 :1999-0 5 -13基金项目 :国家自然科学基金资助项目 ( 3 9170 3 15 ) ;全军医药卫生科研基金资助项目 ( 92 5 0 5 2 )作者简介 :刘　立 ( 195 8-) ,男 (汉族 ) ,江苏省无锡市人 .副教授 ,博士 .Tel.( 0 2 9) 3 3 74819缺血 30 min就可以观察到多形核中性细胞于缺血部位的微血…     

β-阻滞剂塞利洛尔的合成

报道了β－阻滞剂塞利洛尔的简便制备方法，即以对乙氧基苯胺为原料，经酰胺化，傅克反应，以环氧氯丙烷取代，最后用叔丁胺直接与环氧基反应开环等４步反应制得。比文献五步反应缩短了一步，产物经元素分析、红外光谱、核磁共振谱、质谱等分析确定结构。     

羧乙基锗倍半氧化物对正常和异丙基肾上腺素损伤培养乳鼠心肌细胞的影响

羧乙基锗倍半氧化物(Ge—132)能促进培养乳鼠心肌细胞DNA和RNA的合成,提高超氧化物歧化酶(SOD)的活性,维持细胞膜结构的稳定。异丙基肾上腺素可使心肌细胞乳酸脱氢酶(LDH)释放增加,细胞搏动停止,超微结构显示肌膜和线粒体严重受损。Ge—132可显著减少异两基肾上腺素引起心肌细胞释放LDH,维持细胞的搏动功能和超微结构的完整。