Comparison of 125I-interferon-alpha binding to peripheral blood cells from African-Americans and Caucasians with hepatitis C

Interferon-alpha (IFN-alpha) is the major treatment for chronic hepatitis C virus (HCV) infection. Drug resistance is problematic, particularly among African-Americans who typically show poorer clinical outcomes than Caucasians. The reasons for ethnic variation in IFN-alpha sensitivity are not clear. We speculated that African-American insensitivity to IFN-alpha may be mediated by reduced density of the IFN-alpha receptor (IFN-alphaR) or reduced internalization of the IFN-alpha/IFN-alphaR complex. This speculation was evaluated by comparing binding, uptake and release of 125iodine-labelled IFN-alpha (125I-IFN-alpha) to peripheral blood cells from African-Americans and Caucasians with HCV infection and ethnically matched healthy volunteers. Under various in vitro conditions, binding of 125IFN-alpha to surface receptors was equivalent (P = ns) between African-Americans and Caucasians with HCV infection as well as healthy volunteers (P = ns). Similarly, internalization and release of the 125I-IFN-alpha/IFN-alphaR complex was equivalent (P = ns) between African-Americans and Caucasians with HCV infection and healthy volunteers (P = ns). In addition, ethnicity did not influence (P = ns) IFN-alpha suppression of phytohaemagluttinen induced proliferation. However, IFN-alpha therapy of the same patients showed that African-Americans had lower response rates than Caucasians (14%vs 54%, P < 0.0001). In summary, IFN-alpha resistance among African-Americans is not mediated by intrinsic differences in IFN-alpha receptor density or internalization.     

老年性骨质疏松所致骨折患者血清钙磷和TGF-β 1分析

1临床资料2003-06／2004—12收治髋部骨质疏松性骨折患20(男14，女6)例，年龄58—80(平均68．5)岁，股骨颈骨折13例，粗隆间骨折7例．对照组为老年性骨关节病或颈腰椎病患20例．均抽空腹静脉血4mL，3000r／min离心5min分离血清，4h内测定血清钙、磷，留血清-20℃保存备用，测定TGF-β1．用Au-2700全自动生化分析仪测定血清钙、磷，试剂由日本欧林巴斯公司提供．血清TGF-β1检测采用ELISA法，     

胰岛素样生长因子-I和人绒毛膜促性腺激素对成年大鼠Leydig细胞葡萄糖转运蛋白基因表达调控

目的:研究胰岛素样生长因子I(IGF I)和人绒毛膜促性腺激素(hCG)对成年大鼠睾丸Leydig细胞中葡萄糖转运蛋白(GLUT)基因表达的影响,为进一步探讨Leydig细胞中睾酮的合成、分泌与葡萄糖代谢的关系提供依据。方法:采用改良的Klinefelter方法从成年大鼠睾丸中分离获得Leydig细胞;用反转录聚合酶链技术检测IGF I和hCG对原代培养的Leydig细胞中GLUT基因表达的调控作用。结果:分离得到纯度为98%的大鼠Leydig细胞,并与对照组比较,hCG可显著增加Leydig细胞中GLUT8基因mRNA的表达水平(P<0.001),且此作用具有剂量依赖性与时效性。当在试验组细胞中单独加入IGF I或IGF I和hCG作用于细胞后,发现IGF I(100ng mL)可显著增加Leydig细胞中GLUT8基因mRNA的表达(P<0.01),也可与hCG协同作用显著提高GLUT8基因的mRNA表达,该结果与IGF I(100ng mL)和hCG(10ng mL)能协同作用极显著增加睾酮合成水平(P<0.001)的结果是相吻合的。在大鼠Leydig细胞中,无论10ng mL或100ng mL还是两者同时作用于细胞,都不能影响GLUT1和GLUT3基因的mRNA水平。结论:在成年大鼠Leydig细胞中,IGF I和hCG对细胞中的GLUT8基因表达的调节作用具有特异性,其协同作用能显著提高细胞中GLUT8基因mRNA水平,增强细胞摄取葡萄糖的能力,给细胞提供更多的代谢能源,最终增加Leydig细胞睾酮的合成与分泌。     

Measuring nicotine dependence among youth: a review of available approaches and instruments

This paper reviews issues and concepts related to the measurement of nicotine dependence among youth. The primary objectives of this review are to: (1) review the measures of nicotine dependence currently being used; and (2) delineate a future research agenda in an attempt to advance the quality of measurement and instrumentation for this important research endeavor. Existing measures of nicotine dependence, including formal diagnostic interviews, related withdrawal assessments, brief self-report measures, and single-item indicators, are described. While formal diagnostic systems have been considered the 'gold standard' for evaluating dependence clinically, their specific limitations related to use for research purposes are outlined. Each broad class of measure is evaluated in terms of its rationale for use, strengths and limitations, and the extent to which it has successfully been applied to adolescent populations. A research agenda follows in the second section of the paper. In this section, the need for identification and inclusion of a standard set of optimal dependence measures, for enhancement of current measures, and for the onset of a new and comprehensive measures development program is outlined.     

Approach to the management of patients with chronic hepatitis C who failed to achieve sustained virologic response

The combination of peginterferon and ribavirin is the most effective therapy for patients with chronic hepatitis C virus (HCV) infection. Although more than half of all patients are able to achieve a sustained virologic response (SVR), a significant proportion of patients, particularly those with genotype 1, fail to have undetectable HCV RNA during treatment or relapse after completing therapy with return of detectable HCV RNA. The management of these patients creates a formidable challenge. This article outlines various strategies for patients who have failed to achieve SVR and discusses the merits of different approaches to management.