Investigation of the metabolism and reductive activation of carcinogenic aristolochic acids in rats.

The metabolic activation of aristolochic acids (AAs) that have been demonstrated to be mutagenic and carcinogenic was investigated. In vitro metabolism study indicated that AAs were metabolized to N-hydroxyaristolactam, which could be either reduced to aristolactams or rearranged to 7-hydroxyaristolactams via the Bamberger rearrangement. In vivo metabolism study is important because the intermediates (aristolactam-nitriumion) of the nitroreduction process are thought to be responsible for the carcinogenicity of AAs. Liquid chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry (MS/MS) were applied to the analyses of a series of positional isomers of hydroxyaristolactams in rat urine samples after the in vivo study of AAs. Three hydroxylated metabolites of aristolactam II and two hydroxylated metabolites of aristolactam I were identified. The structures of the positional isomers were elucidated from the interpretation of MS/MS spectra and theoretical calculations. In addition, several new metabolites were detected in the rat urine by high-resolution mass spectrometry and MS/MS, including those from the decarboxylation of AAs and the conjugations of acetylation, glucuronidation, and sulfation of aristolochic acid Ia.     

银杏叶提取物与刺梨不同比例配伍银杏酸的含量比较

目的 通过测定银杏叶提取物与刺梨不同比例配伍银杏酸的含量,探讨复方银杏叶制剂配伍减毒的机制.方法 采用RP-HPLC法,选用汉邦Kromasil C18色谱柱,甲醇-3%HAc水溶液(92:8)为流动相,检测波长312 nm,流速1.0 ml/min.结果 银杏酸在0.08～0.64 μg范围内有良好的线性关系,平均回收率为97.65%,RSD为1.5%;刺梨与银杏叶提取物配伍后,银杏酸的含量较配伍前明显降低,随添加刺梨比例不同,银杏酸含量呈一定的变化趋势,当刺梨与银杏叶提取物比例达2:1时,银杏酸含量最低.结论 刺梨与银杏叶配伍后,可降低制剂中银杏酸的含量.     

我国氨基酸类药物研究进展

氨基酸是一类具有特殊生理功能的小分子化合物,近年来我国氨基酸类药物发展迅速,总结市场和研究情况,今后小肽、氨基酸螯合物以及氨基酸衍生物可能成为氨基酸类原料药发展的新方向;而复方氨基酸制剂则可能偏重于含谷氨酰胺的营养输液、肠内营养制剂和多腔袋营养制剂的开发。     

早期宫颈癌患者根治术后辅助治疗的临床研究

目的探讨早期宫颈癌年轻患者根治术后辅助治疗的临床意义。方法回顾性分析Ⅰb期宫颈癌年轻患者根治术后加用放疗或化疗辅助治疗48例,其中术后放疗30例,术后化疗18例。结果放疗组与化疗组的3年生存率分别为93.3%和88.9%,两者之间差异无统计学意义(P>0.05),放疗组并发症及不良反应明显高于化疗组,各项指标之间差异有统计学意义。结论年轻Ⅰb期宫颈癌患者术后加用化疗在不影响生存率的前提下,生存质量得以提高,是比较合理有效的治疗方法。     

"旴江医学"印象

旴江名医众多，著述浩繁，研究江西“旴江医学”的源流特色、医家及学术特点等相关论述，有一定的现实意义。     

Transgenic expression of the coxsackie/adenovirus receptor enables adenoviral-mediated gene delivery in naive T cells

The inability to easily and efficiently introduce genes into primary T cells has hampered the investigation of the pathways controlling T cell fate. To enable adenoviral-mediated gene transfer into normal naive T cells, transgenic (Tg) mice expressing the coxsackie/adenovirus receptor (CAR) in their T cell compartment were constructed. Whereas naive T cells are resistant to adenoviral infection, Tg expression of CAR on T cells greatly facilitates adenoviral-mediated gene expression ex vivo, in vivo, and in differentiated T helper cells. Thus we have developed a technology for efficient gene delivery to naive T cells. By using adenoviral vectors encoding specific inhibitors, we show that G1 cyclin-dependent kinase, NF-kappaB, and caspase activities are required for the proliferation of primary T cells. In addition, by expressing Bcl-x(L) protein at a level that closely approximates mitogen-induced levels, we demonstrate that Bcl-x(L) expression is sufficient to account for mitogen-mediated survival of primary T cells. Thus, adenoviral-mediated gene delivery to CAR Tg T cells should be useful for the analysis of many genes controlling T cell fate.     

野西瓜果皮中有机酸类化学成分的分离与鉴定

目的研究野西瓜(Capparis spinosa L.)果皮中有机酸类化学成分,为进一步阐明其抗炎抗菌活性成分、充分开发利用提供科学依据。方法采用硅胶柱色谱、羟丙基葡聚糖凝胶柱色谱等方法进行分离纯化,并通过理化常数测定和波谱分析鉴定其化学结构。结果从野西瓜果皮中分离得到了6个有机酸类化合物,即香草酸(vanillic acid,1)、4-羟基苯甲酸(4-hydroxybenzoic acid,2)、原儿茶酸(protocatechuic acid,3)、2,4-二羟基苯甲酸(2,4-dihydroxybenzoic acid,4)、丁二酸(succinic acid,5)、邻苯二甲酸二(2-乙基)己酯(bis(2-ethylhexyl)phthalate,6);分离得到3个甾体类化合物为β-谷甾醇(β-sitosterol,7)、胡萝卜苷(daucosterol,8)、α-菠菜甾醇-3-O-β-D-吡喃葡萄糖苷(α-spinasterol-3-O-β-D-glucopyranoside,9)。结论化合物4、6、9为首次从山柑属植物中分离得到。     

Specific detection of fungal pathogens by 18S rRNA gene PCR in microbial keratitis

Background  

The sensitivity and specificity of 18S rRNA polymerase chain reaction (PCR) in the detection of fungal aetiology of microbial keratitis was determined in thirty patients with clinical diagnosis of microbial keratitis.     

A CpG oligodeoxynucleotide acts as a potent adjuvant for inactivated rabies virus vaccine.

To develop a CpG containing oligodeoxynucleotide (CpG ODN)-enhanced rabies vaccine for stimulating an earlier production of rabies virus neutralizing antibody (RVNAb) with high titers, we designed a CpG ODN (BW006) and evaluated its adjuvant activities in enhancing the immune response to rabies vaccine with or without aluminum in mice. It was found that BW006 could facilitate the rabies vaccine to induce an earlier and more vigorous RVNAb response, resulting in more effective protection of mice from rabies virus challenge. In addition, three shots of rabies vaccine with BW006 induced compatible RVNAb level with that induced by five shots of aluminum-adjuvanted rabies vaccine. These data reveal that BW006 could be used as a promising adjuvant to replace of or combine with aluminum for developing more effective rabies vaccines.     

Improved formulation of photosensitizer chlorin e6 polyvinylpyrrolidone for fluorescence diagnostic imaging and photodynamic therapy of human cancer.

An improved formulation of the photosensitizer chlorin e6 (Ce6) in combination with the hydrophilic polymer polyvinylpyrrolidone (PVP) was investigated for its potential clinical applications in fluorescence diagnosis and photodynamic therapy (PDT) of cancer. This study reports the comparative preclinical biodistribution and efficacy of Ce6 delivered with or without PVP versus dimethyl sulfoxide (DMSO). The safety and fluorescence pharmacokinetics of Ce6-PVP in humans was also accessed. Biodistribution results showed that Ce6-PVP had higher tumor to normal tissue ratio compared to the other formulations. The sensitivity and specificity derived from the area under the receiver operating characteristics curves showed that the formulations were able to discriminate tumor from peritumoral muscle in the following order: Ce6-PVP>Ce6>Ce6-DMSO. In vitro PDT results showed that Ce6-PVP was found to induce selective phototoxicity in leukemic cells compared to peripheral mononuclear blood cells. In addition, in vivo light irradiation at 1h after Ce6-PVP was found to induce greater tumor necrosis without causing animal toxicity. In patients, preferential accumulation of Ce6-PVP was observed in angiosarcoma lesions compared to normal skin following intravenous administration. In conclusion, PVP significantly enhanced the Ce6 concentration in tumors compared with Ce6 alone and increased the therapeutic index of PDT without any side effects in animal model. No serious adverse events were observed in human as well.