高效液相色谱法测定苯甲酸利扎曲普坦片含量及含量均匀度

目的采用高效液相色谱法测定苯甲酸利扎曲普坦片含量及含量均匀度.方法色谱条件为Prodigy ODS C18硅烷键合硅胶填充柱(150 mm×4.6 mm,5 μm);流动相为乙腈-0.025%磷酸二氢钾-三乙胺(36∶264∶1),10%磷酸调pH 5.0;检测波长为225 nm;进样量为20 μL;流速为1.0 mL*min-1.结果在进样量为0.101～1.01 μg,样品浓度和峰面积成良好线性关系,r=0.999 9,平均回收率为101.20%,RSD为2.2%. 结论方法灵敏可靠,选择性高.     

N-desmethylclozapine, a major metabolite of clozapine, increases cortical acetylcholine and dopamine release in vivo via stimulation of M1 muscarinic receptors.

The active moiety of clozapine, the prototypical antipsychotic drug, consists of clozapine and its major metabolite, N-desmethylclozapine (NDMC). Previous studies have suggested that NDMC may be more important than the patent compound itself for the improvement in cognition in patients with schizophrenia treated with clozapine. While the pharmacology of clozapine and NDMC are similar in most respects, NDMC has been shown to be an M1 muscarinic receptor partial agonist whereas clozapine is an M1 antagonist in vitro and in vivo. We hypothesized that NDMC may improve cognition by increasing dopamine (DA) and acetylcholine (ACh) release in medial prefrontal cortex (mPFC) via direct stimulation of M1 receptors, whereas both NDMC and clozapine itself would do so by other mechanisms as well, and that clozapine would inhibit the M1 agonist effect of NDMC. In the present study, using microdialysis in awake, freely moving rats, we found that NDMC at doses of 10 and 20, but not 5 mg/kg, significantly increased DA and ACh release in the mPFC and HIP, but not in the nucleus accumbens (NAC). The M1-preferring antagonist, telenzepine (3 mg/kg), completely blocked NDMC (10 mg/kg)-induced increases in cortical DA and ACh release. Clozapine (1.25 mg/kg), which by itself had no effect on DA or ACh release in the cortex, blocked NDMC (10 mg/kg)-induced ACh, but not DA, release in the mPFC. The 5-HT1A receptor antagonist, WAY100635 (0.2 mg/kg) blocked NDMC (20 mg/kg)-induced cortical DA but not ACh release. These findings suggest that: (1) NDMC is an M1 agonist while clozapine is an M1 antagonist in vivo; (2) M1 agonism of NDMC can contribute to the release of cortical ACh and DA release; (3) NDMC, because of its M1 agonism, may more effectively treat the cognitive impairments observed in schizophrenia than clozapine itself; and (4) M1 receptor agonism may be a valuable target for the development of drugs that can improve cognitive deficit in schizophrenia, and perhaps other neuropsychiatric disorders as well.     

芪丹颗粒剂治疗肺间质纤维化105例临床研究

目的:观察芪丹颗粒剂对肺间质纤维化患者的临床疗效.方法:选择105例肺间质纤维化患者作为治疗组,给予芪丹颗粒剂,对照组60例,给予强的松0.5mg/kg,两组疗程均为3～6个月,每1～3个月随诊1次.观察两组患者治疗后的症状、体征、肺部高分辨率CT(HRCT)及肺功能变化.结果:治疗6个月后,治疗组症状、体征改善率优于对照组(P＜0.05或P＜0.01);治疗组治疗3个月和6个月后,肺HRCT和肺功能改善率优于对照组(P＜0.05或P＜0.01).结论:芪丹颗粒剂可以不同程度地改善肺间质纤维化患者症状和体征,使患者肺功能停止恶化,且用药期间未见任何副作用,耐受性良好.     

胃癌中医证型与胃癌转移相关基因E-cadherin的关系研究

目的:从基因蛋白表达上探索胃癌患者中医证的本质.方法:将收集到的术前胃癌患者病例资料按中医辨证分型标准确定其证型归属;用免疫组化EnVision二步法检测术后胃癌肿瘤标本中E-cadherin基因蛋白表达情况.结果:E-cadherin在100例胃癌患者中的阳性表达率为90%,证型间表达差异存在显著性(P<0.01);进一步两两比较示,痰湿凝结型、气血双亏型与脾胃虚寒型之间无明显差异,表达较高;瘀毒内阻型与肝胃不和型无明显差异,表达较低.结论:瘀毒内阻型与肝胃不和型胃癌患者的E-cadherin表达偏低,此两种证型肿瘤转移形成的途径可能与E-cadherin,即与肿瘤细胞间同质性黏附力降低相关.     

黄精多糖对新生大鼠大脑皮层神经细胞缺氧性凋亡的影响

目的:探讨黄精多糖对体外培养的新生大鼠大脑皮层神经细胞缺氧性凋亡的保护作用.方法:采用"Neurobasal加B27 Supplement"体外培养新生大鼠大脑皮层神经细胞,使用Hoechst 33342荧光染色、免疫细胞化学染色观察黄精多糖对缺氧复氧性神经细胞凋亡的保护作用.结果:缺氧前加入500μg/ml～1.5mg/ml的黄精多糖能显著地降低缺氧复氧培养诱导的神经细胞凋亡率,增加缺氧的神经细胞Bcl-2蛋白的表达,减少Bax蛋白的表达,提高Bcl-2/Bax比值.而缺氧12h后加入黄精多糖则无明显的抗凋亡作用.结论:缺氧前加入黄精多糖可以通过上调缺氧神经细胞Bcl-2表达、下调Bax表达和提高Bcl-2/Bax的比值以避免缺氧的神经细胞凋亡.     

肾气-天癸-冲任-胞宫生殖轴与月经的关系浅谈

女性生殖轴在一生中运转30年左右的时间，从而维持月经周期性节律变化。而在这时期月经是靠肾气-天癸-冲任-胞宫相互作用来完成的。     

Green tea extract modulates actin remodeling via Rho activity in an in vitro multistep carcinogenic model.

Alteration of actin polymerization and loss of actin filaments is a marker of cellular dedifferentiation and early malignant transformation. To study this phenomenon, an in vitro human urothelial model consisting of two cell lines, HUC-PC and MC-T11, were incorporated into the study design. These two cell lines have different malignant transformation potential. The effect of green tea extract (GTE), a potential anticancer agent, on actin remodeling was investigated. Upon exposure to the carcinogen 4-aminobiphenyl (4-ABP), the untransformed HUC-PC undergoes malignant transformation whereas the transformed MC-T11 progresses from noninvasive to invasive tumor. GTE induces actin polymerization in MC-T11 cells in a dose-responsive manner, but this effect is less obvious in the untransformed, more differentiated HUC-PC cells, which natively have higher actin polymerization status. In contrast, GTE antagonizes carcinogen 4-ABP induced actin depolymerization and stress fiber disruption in HUC-PC cells. In MC-T11 cells, GTE inhibits 4-ABP induced motility by increasing cell adhesion and focal adhesion complex formation. The effect of GTE on actin remodeling seems to be mediated by the stimulation of small GTP-binding protein Rho activity, because C3 exoenzyme, a specific inhibitor for Rho, blocks GTE-mediated Rho activation and stress fiber formation in MC-T11 cells. This study shows that GTE exerts an effect on cytoskeletal actin remodeling and provides further support for the use of GTE as a chemopreventive agent.     

Vascular endothelial growth factor gene polymorphisms and risk of primary lung cancer.

Angiogenesis is an essential process in the development, growth, and metastasis of malignant tumors including lung cancer. DNA sequence variations in the vascular endothelial growth factor (VEGF) gene may lead to altered VEGF production and/or activity, thereby causing interindividual differences in the susceptibility to lung cancer via their actions on the pathways of tumor angiogenesis. To test this hypothesis, we investigated the potential association between three VEGF polymorphisms (-460T > C, +405C > G, and 936C > T)/haplotypes and the risk of lung cancer in a Korean population. VEGF genotypes were determined in 432 lung cancer patients and 432 healthy controls that were frequency matched for age and sex. VEGF haplotypes were predicted using Bayesian algorithm in the phase program. Compared with the combined +405 CC and CG genotype, the +405 GG genotype found associated with a significantly decreased risk of small cell carcinoma [SCC; adjusted odds ratio (OR), 0.36; 95% confidence interval (95% CI), 0.17-0.78]. The 936 CT genotype and the combined 936 CT and TT genotype were also associated with a significantly decreased risk of SCC compared with the 936 CC genotype (adjusted OR, 0.47; 95% CI, 0.26-0.85 and adjusted OR, 0.44; 95% CI, 0.24-0.80, respectively). Haplotype CGT was associated with a significantly decreased risk of SCC (adjusted OR, 0.39; 95% CI, 0.18-0.87), whereas haplotype TCC conferred a significantly increased risk of SCC (adjusted OR, 1.63; 95% CI, 1.14-2.33). None of the VEGF polymorphisms studied significantly influenced the susceptibility to lung cancer except SCC. However, haplotypes TCT and TGT were significantly associated with the risk of overall lung cancer, respectively (adjusted OR, 0.38; 95% CI, 0.25-0.60 and adjusted OR, 3.94; 95% CI, 2.00-7.76, respectively). These effects of haplotypes TCT and TGT on lung cancer risk were observed in three major histologic types of lung cancer. These results suggest that the VEGF gene may be contribute to an inherited predisposition to lung cancer.