Natural allelic variants of bovine ATP-binding cassette transporter ABCG2: increased activity of the Ser581 variant and development of tools for the discovery of new ABCG2 inhibitors

ATP-binding cassette transporter ABCG2 [breast cancer resistance protein (BCRP)] is a member of the ABC transporter superfamily that actively extrudes xenotoxins from cells and is a major determinant of the bioavailability of many compounds. ABCG2 expression is strongly induced during lactation in the mammary gland and is related to the active secretion of drugs into the milk. The presence of drug residues and environmental pollutants in milk is an outstanding problem for human milk consumption and milk industrial processes, involving important risks to public health and the dairy industry. In cows, a single nucleotide polymorphism (SNP) in this protein has been described previously (Tyr581) and is associated with higher fat and protein percentages and lower milk yield. However, whether this amino acid substitution affects ABCG2-mediated drug transport in cows, including milk secretion, required further exploration. We cloned the two variants of bovine ABCG2 and evaluated the effect of this SNP on mitoxantrone accumulation assays performed in ovine primary fibroblasts transiently expressing either of the variants. It is interesting to note that statistically significant differences in activity between both variants were observed, and the Ser581 variant was related with an increased efflux activity. In addition, we demonstrated that genistein is a very good inhibitor of bovine ABCG2 and identified new inhibitors of the transporter, such as the macrocyclic lactones, ivermectin, and selamectin. Moreover, the inhibitory effect of these compounds on human and murine ABCG2 homologs was confirmed using transduced Marbin-Dabin canine kidney II cells. These findings may have important implications regarding the presence of drug residues in milk and drug interactions affecting the pharmacological behavior of ABCG2 substrates.     

聚乙二醇干扰素α-2b或α-2a与利马韦林联合治疗丙型肝炎疗效比较

背景及目的：丙型肝炎的治疗指南推荐聚乙二醇干扰素α-2b或α-2a联合利巴韦林治疗.但是,这两种方案并没有进行充分地比较,本研究通过临床观察对其疗效进行分析探讨.     

How relevant is the Cochrane Database of Systematic Reviews to nursing care?

Barriers obstructing evidence‐based nursing have been explored in many countries. Lack of resources and evidence has been noted as one of these barriers. We aimed to identify nursing care‐related systematic reviews published in the Cochrane Database of Systematic Reviews from 1996 until 2009. Using a broad search strategy we identified titles of Cochrane systematic reviews and protocols that focused on nursing care. The abstract of each title was examined and predetermined data were collected and analysed. 1249 titles out of a possible 6244 records were identified as being relevant to nursing care. Most of them focused on newborn and adult populations and related to comparing one intervention with another, and management strategies. The most common nursing specialties represented were internal medicine (34%) and mother and child care (25%). Twenty one percent of reviews published in the Cochrane Database of Systematic Reviews are of direct interest to those involved in nursing care however their relevance was not always obvious.     

中药材X-射线衍射图谱研究

为探讨中药材道地性的客观规律,以期建立相应的评估指标系统,本文选择常用中药材茜草类、贝母类、山药类三组样品,应用X-射线粉末衍射法进行图谱分析,获得了可用于标识中药材的衍射图形几何拓扑规律与图谱特征标记峰,由此观察到:不同产地茜草样品的相似性及其与欧茜草的差别;同属不同种贝母样品的相似性与差异;不同产地山药样品的相似性及与伪品的区别。本文结果预示着这一方法在揭示中药材道地性客观规律方面的广阔应用前景。