Effect of chronic treatment with Rosiglitazone on Leydig cell steroidogenesis in rats: <Emphasis Type="Italic">In vivo</Emphasis> and <Emphasis Type="Italic">ex vivo</Emphasis> studies

Background  

The present study was designed to examine the effect of chronic treatment with rosiglitazone - thiazolidinedione used in the treatment of type 2 diabetes mellitus for its insulin sensitizing effects - on the Leydig cell steroidogenic capacity and expression of the steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage enzyme (P450scc) in normal adult rats.     

Selected anthropometric variables and aerobic fitness as predictors of cardiovascular disease risk in children

The aim of this study was to assess the suitability of body mass index, waist circumference, waist-to-height ratio and aerobic fitness as predictors of cardiovascular risk factor clustering in children. A cross-sectional study was conducted with 290 school boys and girls from 6 to 10 years old, randomly selected. Blood was collected after a 12-hour fasting period. Blood pressure, waist circumference (WC), height and weight were evaluated according to international standards. Aerobic fitness (AF) was assessed by the 20-metre shuttle-run test. Clustering was considered when three of these factors were present: high systolic or diastolic blood pressure, high low-density lipoprotein (LDL) cholesterol, high triglycerides, high plasma glucose, high insulin concentrations and low high-density lipoprotein (HDL) cholesterol. A ROC curve identified the cut-off points of body mass index (BMI), WC, waist-to-height ratio (WHtR) and AF as predictors of risk factor clustering. BMI, WC and WHR resulted in significant areas under the ROC curves, which was not observed for AF. The anthropometric variables were good predictors of cardiovascular risk factor clustering in both sexes, whereas aerobic fitness should not be used to identify cardiovascular risk factor clustering in these children.     

Worldwide experience with biosimilar development

Limited access for high-quality biologics due to cost of treatment constitutes an unmet medical need in the US and other regions of the world. The term “biosimilar” is used to designate a follow-on biologic that meets extremely high standards for comparability or similarity to the originator biologic drug that is approved for use in the same indications. Use of biosimilar products has already decreased the cost of treatment in many regions of the world and now a regulatory pathway for approval of these products has been established in the US. The Food and Drug Administration (FDA) led the world with the regulatory concept of comparability and the European Medicines Agency (EMA) was the first to apply this to biosimilars. Patents on the more complex biologics, especially monoclonal antibodies, are now beginning to expire and biosimilar versions of these important medicines are in development. The new Biologics Price Competition and Innovation Act (BPCIA) allows the FDA to approve biosimilars and allows the FDA to lead on the formal designation of interchangeability of biosimilars with their reference products. The FDA''s approval of biosimilars is critical to facilitating patient access to high-quality biologic medicines and will allow society to afford the truly innovative molecules currently in the global biopharmaceutical industry''s pipeline.Key words: monoclonal antibodies (mAbs), biosimilars, recombinant biopharmaceuticals     

抗肿瘤药阿霉素诱导Wnt通路抑制因子的表达

研究抗肿瘤药阿霉素对Wnt通路抑制因子FrpHE(frizzled-related protein)和DKK-1(Dickkopf-1)表达的作用.将抗肿瘤药阿霉素加入到人肝癌HepG2(HepG2,含野生型p53;Hep3B,p53缺失)、人大肠癌(Lovo,含野生型p53)和人神经胶质瘤细胞(U251,p53突变)细胞株中.以RT-PCR技术检测阿霉素对Wnt通路抑制因子FrpHE和DKK-1的表达调节作用,以流式细胞术检测在肿瘤细胞中Wnt通路的关键调节因子β-catenin的表达.在加入阿霉素24h后FrpHEmRNA表达水平在人肝癌细胞(HepG2,含野生型p53;Hep3B,p53缺失)中与对照组相比表达水平显著增加.在人大肠癌细胞(Lovo,含野生型p53)和人神经胶质瘤细胞(U251,p53突变型)细胞中,未见FrpHE mRNA表达.DKK-1mRNA表达水平在人肝癌细胞(HepG2,含野生型p53;Hep3B,p53缺失)、人大肠癌细胞(Lovo,含野生型p53)和人神经胶质瘤细胞(U251,p53突变型)中与对照组相比表达水平显著增加.β-catenin的阳性细胞百分比强度和平均荧光量强度与对照组相比,表达水平降低.提示化疗药阿霉素能明显诱导抑制剂FrpHEmRNA和DKK-1mRNA的表达.