氟氯西林镁颗粒的人体生物等效性研究

目的:比较氟氯西林镁颗粒与氟氯西林钠胶囊的人体生物等效性。方法:24名健康受试者随机分为两组,采用双周期自身交叉方法,单剂量口服受试制剂氟氯西林镁颗粒或参比制剂氟氯西林钠胶囊0.5 g。用液-质联用(LC-MS/MS)法测定氟氯西林的血浆浓度,并计算其药动学参数,比较二者的人体生物等效性。结果:受试制剂与参比制剂的药动学参数分别为:t1/2(1.53±0.29)、(1.55±0.25)h,cmax(34.56±8.13)、(34.67±8.89)mg/L,tmax(0.72±0.25)、(0.74±0.25)h,AUC0-24 h(69.51±15.34)、(70.47±16.19)mg·h/L,受试制剂的相对生物利用度为(99.29±10.34)%。结论:氟氯西林镁颗粒与氟氯西林钠胶囊在吸收程度上具有生物等效性。     

Role of AMPK in pancreatic beta cell function

Pharmacological activation of AMP activated kinase (AMPK) by metformin has proven to be a beneficial therapeutic approach for the treatment of type II diabetes. Despite improved glucose regulation achieved by administration of small molecule activators of AMPK, the potential negative impact of enhanced AMPK activity on insulin secretion by the pancreatic beta cell is an important consideration. In this review, we discuss our current understanding of the role of AMPK in central functions of the pancreatic beta cell, including glucose-stimulated insulin secretion (GSIS), proliferation, and survival. In addition we discuss the controversy surrounding the role of AMPK in insulin secretion, underscoring the merits and caveats of methods used to date.     

益气温阳、活血利水法对充血性心力衰竭的辅助治疗作用

【目的】研究益气温阳、活血利水中药对常规西药治疗充血性心力衰竭(简称心衰)的协同作用及其对神经内分泌因子的影响。【方法】将心功能为Ⅱ~Ⅳ级,中医辨证属气(阳)虚血瘀兼水饮证的心衰患者70例随机分为西医常规治疗组(简称西药组,28例)和常规治疗加中药组(简称中西药组,42例)。两组均给予地高辛、利尿剂、血管紧张素转换酶抑制剂、β受体阻滞剂等常规抗心衰治疗,中西药组在此基础上给予益气温阳、活血利水中药(药物组成:生黄芪、太子参、仙灵脾、仙茅、葶苈子、益母草、桃仁、茯苓、泽泻、桂枝、炒酸枣仁、甘草)口服治疗,4周为1个疗程。观察两组临床疗效及治疗前后心功能、神经内分泌因子的变化情况。【结果】中西药组显效24例,有效16例,无效2例,总有效率为95.24%;西药组显效19例,有效4例,无效5例,总有效率为82.14%;两组比较,中西药组疗效优于西药组(P<0.01)。在心功能变化方面,两组治疗后左室射血分数(EF)、左室短轴缩短率(FS)、心脏指数(CI)等参数与治疗前比较均有显著性差异(P<0.01),中西药组EF、CI的改善较西药组明显(P<0.01)。在神经内分泌因子的变化方面,两组治疗后血中的心房肽(ANP)、血管紧张素Ⅱ(AT-Ⅱ)、内皮素(EF)水平均较治疗前下降(P<0.05),且中西药组较西药组下降更明显(P<0.05)。【结论】益气温阳、活血利水中药对心衰有辅助治疗作用,其机理可能与其协同西药有效降低血中ANP、AT-Ⅱ、ET等神经内分泌因子水平有关。     

四君子汤合小建中汤治疗胃肠道恶性肿瘤手术和化疗后45例临床观察

目的:观察四君子汤合小建中汤缓解胃肠道恶性肿瘤患者手术和辅助化疗后虚证临床证候及其免疫调节作用。方法:90例病人随机分为治疗组和对照组各45例,治疗组采用四君子汤合小建中汤治疗,对照组采用单纯西药治疗。结果:治疗组在改善胃肠道恶性肿瘤患者虚证证候、提高和调节免疫功能等方面明显优于对照组,且与对照组之间有显著或较显著性差异(P<0.01或0.05)。结论:四君子合小建中汤能较好地缓解胃肠道恶性肿瘤患者由于手术和化疗等因素引起的虚证证候,并能提高或调节其免疫功能。     

JIP影响鼻咽癌细胞增殖和凋亡的生物学效应研究

背景与目的：研究表明LMP1激活c-Jun N末端激酶（c-Jun N-ternimal kinase,JNK)介导的信号途径在促进鼻咽癌的发生发展有重要作用,并且发现JNK相互作用蛋白（JNK interacting protein,JIP)在鼻咽癌细胞中能够有效抑制JNK信号途径。本实验在此基础上进一步研究JIP对鼻咽癌细胞增殖和凋亡生物学效应的影响。方法：采用MTT法观察不同剂量的JIP及相同剂量JIP作用不同时间后鼻咽癌细胞生长情况;并用集落形成率确定单个鼻咽癌细胞的增殖能力;同时用流式细胞术分析JIP作用不同时间后鼻咽癌细胞生长情况;并用集落形成率确定单个鼻咽癌细胞的增殖能力;同时用流式细胞术分析JIP作用前后细胞周期时相的变化;最后通过流式细胞术检测JIP作用后鼻咽癌细胞凋亡百分率的改变。结果：（1）随着转染JIP量的增加,细胞的存活率逐渐下降,存在剂量依赖效应;1μg/ml JIP作用24、48、72h后,细胞存活率分别为77．8％、59．2％、61．8％。（2）转染JIP后鼻咽癌细胞形成的集落明显减少,且集落体积变小。（3）转染JIP使鼻咽癌细胞周期G0／G1期细胞百分率由66．24％上升到71．89％,S期细胞百分率由25．87％下降到19．96％。（4）与对照组相比,转染JIP后细胞的24h 凋亡百分率由1．25％上升到8．25％,上升约6．6倍,48h由1．04％上升到31．45％,上升约30倍。结论：JIP能够有效抑制鼻咽癌细胞生长增殖,引起鼻咽癌细胞周期G1／S期延长,并明显促进鼻咽癌细胞凋亡,提示JIP是治疗鼻咽癌潜在的分子药物。     

Cell death in the normal developing brain, and following ionizing radiation, methyl-azoxymethanol acetate, and hypoxia-ischaemia in the rat

Naturally occurring (programmed) cell death in the developing brain has morphological characteristics of apoptosis and is associated with internucleosomal DNA fragmentation. Apoptosis also plays a role in cell death following hypoxia-ischaemia in the developing rat brain. Ionizing radiation-induced cell death in the brain of the young rat has morphological characteristics of apoptosis. is mediated by protein synthesis and is associated with internucleosomal UNA fragmentation. Methylazoxymethanol (MAM) acetate injection in the young rat produces apoptotic cell death in the external granule cell layer of the cerebellum. In addition, strong c-Jun immunore-activity is observed in apoptotic cells during normal development and following experimentally induced cell death. Moreover, c-Jun mRNA induction and de novo c-Jun protein synthesis, together with activation of c-Jun/AP-1, as revealed with gel mobility shift assay, occurs in irradiated animals. Western blotting of total brain homogenates shows a c-Jun-immunoreactive band at p39, which corresponds to the molecular weight of c-Jun. in control rats. However, a thick c-Jun-immunoreactive band at about p62, accompanied by a decrease of the p39 band, occurs in irradiated and MAM-treated rats. A thin band immediately above the thick p62 band, suggestive of c-Jun phosphorylation, is also observed in treated rats. Taken together, these observations indicate that c-Jun expression is associated with apoptotic cell death in the developing central nervous system.     

Inhibition of the c-Jun N-terminal kinase signaling pathway influences neurite outgrowth of spiral ganglion neurons in vitro

OBJECTIVES: Inhibitors of the c-Jun N-terminal kinase (JNK) signaling pathway have been demonstrated to protect hair cells of the auditory system and different types of neurons from various insults, and their use for future therapeutic applications has been proposed. In the study, we evaluated the effects of inhibition of the JNK pathway on process outgrowth from spiral ganglion neurons. METHODS: Spiral ganglion explants from rats (postnatal days 3-5) that were cultured on laminin were treated with neurotrophin-3 and/or the JNK signaling pathway inhibitor CEP-11004. Both neurite length and number of the explants were evaluated and statistically analyzed by analysis of variance. RESULTS: Inhibition of the JNK signaling pathway reduced process outgrowth from spiral ganglion explants. The reduction, both in length and number of neurites, was reversed by the application of neurotrophin-3. CONCLUSIONS: The results indicate that an intact JNK signaling pathway is important for process outgrowth of spiral ganglion neurons. However, neurotrophin-3 stimulates process extension by a JNK independent pathway. Our results demonstrate that inhibition of the JNK pathway can have adverse effects on the extension of spiral ganglion neurons, but that the negative effects can be ameliorated by appropriate treatment.     

Apoptosis in male germ cells in response to cyclin A1-deficiency and cell cycle arrest

Male mice homozygous for a mutated allele of the cyclin A1 gene (Ccna1) are sterile due to a block in cell cycle progression before the first meiotic division. Meiosis arrest in Ccna1(-/-) spermatocytes is associated with desynapsis abnormalities, lowered MPF activity, and apoptosis as evidenced by TUNEL-positive staining. With time, adult testicular tubules exhibit severe degeneration: some tubules in the older animals are almost devoid of germ cells at various stages of spermatogenesis. The mechanisms by which the cells sense the cell cycle arrest and the regulation of the decision to undergo cell death are under investigation.