目的通过比较不同细胞类型之间胰腺十二指肠同源盒1（Pdx-1）、配对盒基因4（Pax4）、MafA（mast cell function associated antigen）和Nkx6．1等胰岛组织特异性基因其转录起始区的H3K4m3和H3K9m3修饰的差异，探讨H3K4nd和H3K9m3修饰...目的通过比较不同细胞类型之间胰腺十二指肠同源盒1（Pdx-1）、配对盒基因4（Pax4）、MafA（mast cell function associated antigen）和Nkx6．1等胰岛组织特异性基因其转录起始区的H3K4m3和H3K9m3修饰的差异，探讨H3K4nd和H3K9m3修饰对胰岛组织特异性基因表达的作用。方法采用染色质免疫共沉淀．实时定量聚合酶链反应（PCR）法检测小鼠胚胎干细胞（mES，1×10^7）、小鼠成纤维细胞株NIH3T3细胞（1×10^7）和小鼠B细胞株NIT-1细胞（1×10^7）三者中的胰岛组织特异性基因、Oct4基因和MLH1基因转录起始区H3K4rrd和H3K9m3修饰的状况。同时采用实时定量逆转录（RT）-PCR检测上述3种细胞各基因mRNA表达水平。分析H3K4m3和H3K9m3修饰改变与基因表达之间的关系。结果NIT-1细胞中Pdx-1、Pax4、MafA、Nkx6．1等胰岛组织特异性基因转录起始区的H3K4m的修饰水平分别为：（4．84±0．05）％、（9．91±1．33）％、（10．64±0．87）％、（0．23±0．03）％，与mES细胞比较明显增高（P〈0．05），基因表达；NIH3T3细胞中Pdx-1、Pax4、MafA、Nkx6．1等胰岛组织特异性基因转录起始区的H3Kgm3的修饰水平分别为：（0．64±0．21）％、（7．04±1．29）％、（0．39±0．10）％、（2．35±0．81）％，与mES细胞比较明显增高（P〈0．05），基因不表达。结论mK4n13与H3K9m3修饰能相互协调，共同调控胰岛组织特异性基因的表达。展开更多
In current decade, pharmaceutical industries of Bangladesh are giving much emphasize on the formulation of time release preparation to treat various chronic diseases in order to decrease the frequency of administratio...In current decade, pharmaceutical industries of Bangladesh are giving much emphasize on the formulation of time release preparation to treat various chronic diseases in order to decrease the frequency of administration and to improve patient compliance. Objectives: The objective of this investigation is to design and evaluate sustained release matrix tablet of Gliclazide by direct compression method employing polymers of hydroxypropylmethyl cellulose (HPMC) derivatives (K15M CR and K4M CR) and to select the optimized formulations and compression process by performing a comparative release kinetic study with a reference product, Diamicron MR (one of the worldwide brand of Gliclazide sustain released tablet manufactured by Servier one of the French pharmaceutical company) tablet. Methods: Release kinetics of Gliclazide matrix tablets were determined using USP paddle method at Phosphate buffer (pH 7.4). The release mechanism was explored and explained with zero order, first order, Higuchi and Korsmeyer model. Result: It is found that formulation with lower polymeric concentration follows Higuchi release kinetics and that the formulation with higher concentration best fits with zero order release kinetics. Among the formulations, F1 and F6 show almost similar dissolution profile with Diamicron MR Tablet, which can be suitable candidates for further in-vivo bioequivalence study. Conclusion: Findings of this investigation suggest that F1 and F6 formulations are potential candidates for further bioequivalence study among other formulations.展开更多
文摘目的通过比较不同细胞类型之间胰腺十二指肠同源盒1（Pdx-1）、配对盒基因4（Pax4）、MafA（mast cell function associated antigen）和Nkx6．1等胰岛组织特异性基因其转录起始区的H3K4m3和H3K9m3修饰的差异，探讨H3K4nd和H3K9m3修饰对胰岛组织特异性基因表达的作用。方法采用染色质免疫共沉淀．实时定量聚合酶链反应（PCR）法检测小鼠胚胎干细胞（mES，1×10^7）、小鼠成纤维细胞株NIH3T3细胞（1×10^7）和小鼠B细胞株NIT-1细胞（1×10^7）三者中的胰岛组织特异性基因、Oct4基因和MLH1基因转录起始区H3K4rrd和H3K9m3修饰的状况。同时采用实时定量逆转录（RT）-PCR检测上述3种细胞各基因mRNA表达水平。分析H3K4m3和H3K9m3修饰改变与基因表达之间的关系。结果NIT-1细胞中Pdx-1、Pax4、MafA、Nkx6．1等胰岛组织特异性基因转录起始区的H3K4m的修饰水平分别为：（4．84±0．05）％、（9．91±1．33）％、（10．64±0．87）％、（0．23±0．03）％，与mES细胞比较明显增高（P〈0．05），基因表达；NIH3T3细胞中Pdx-1、Pax4、MafA、Nkx6．1等胰岛组织特异性基因转录起始区的H3Kgm3的修饰水平分别为：（0．64±0．21）％、（7．04±1．29）％、（0．39±0．10）％、（2．35±0．81）％，与mES细胞比较明显增高（P〈0．05），基因不表达。结论mK4n13与H3K9m3修饰能相互协调，共同调控胰岛组织特异性基因的表达。
文摘目的研究3种沉淀抑制剂(PPI)羟丙基甲基纤维素K4M(Hydroxypropyl methyl cellulose K4M,HPMC K4M)、醋酸羟丙甲纤维素琥珀酸酯MG(Hypromellose Acetate Succinate MG,HPMC AS MG)、聚乙烯己内酰胺-聚醋酸乙烯酯-聚乙二醇接枝共聚物(Polyvinylpyrrolidone,Soluplus)对临床口服剂量下pH值诱导延胡索乙素(dl-THP)过饱和相行为的影响。方法绘制dl-THP的pH值-溶解度相图和p H值转换过程中的去过饱和曲线,用溶解度相图佐证dl-THP相行为,以质量浓度-时间曲线下面积和过饱和度为指标分析沉淀抑制剂对dl-THP相行为的影响;采用偏振光显微镜、差示扫描量热法分析沉淀性质。结果临床给药剂量下,dl-THP在pH值转换过程中最大过饱和度为3.93,随时间推移失去过饱和;HPMC K4M、HPMC AS MG、Soluplus在pH值转换180 min内均能维持过饱和度。HPMC K4M、HPMC AS MG、Soluplus在浓度5%时维持过饱和度分别为1.19、1.89、1.36,浓度20%时为1.30、2.35、1.86、浓度50%时为1.30、2.60、2.07。偏振光显微镜和差示扫描量热法结果表明产生结晶沉淀。结论沉淀抑制剂均能改善pH值诱导延胡索乙素过饱和相行为,且这种改善行为随沉淀抑制剂种类和浓度的不同而不同,HPMC AS MG作用效果最佳。
文摘In current decade, pharmaceutical industries of Bangladesh are giving much emphasize on the formulation of time release preparation to treat various chronic diseases in order to decrease the frequency of administration and to improve patient compliance. Objectives: The objective of this investigation is to design and evaluate sustained release matrix tablet of Gliclazide by direct compression method employing polymers of hydroxypropylmethyl cellulose (HPMC) derivatives (K15M CR and K4M CR) and to select the optimized formulations and compression process by performing a comparative release kinetic study with a reference product, Diamicron MR (one of the worldwide brand of Gliclazide sustain released tablet manufactured by Servier one of the French pharmaceutical company) tablet. Methods: Release kinetics of Gliclazide matrix tablets were determined using USP paddle method at Phosphate buffer (pH 7.4). The release mechanism was explored and explained with zero order, first order, Higuchi and Korsmeyer model. Result: It is found that formulation with lower polymeric concentration follows Higuchi release kinetics and that the formulation with higher concentration best fits with zero order release kinetics. Among the formulations, F1 and F6 show almost similar dissolution profile with Diamicron MR Tablet, which can be suitable candidates for further in-vivo bioequivalence study. Conclusion: Findings of this investigation suggest that F1 and F6 formulations are potential candidates for further bioequivalence study among other formulations.
