Treatment of adrenocortical carcinoma: a case report and review of the literature

A case report of adrenocortical carcinoma is presented, and its natural history and treatment are discussed. Adrenocortical carcinoma is a rare malignant disease. The mean survival time for untreated patients is less than three months. The tumor is classified as functioning or nonfunctioning depending on biochemical and clinical evidence of steroid overproduction. Surgical resection of the tumor is the primary treatment. Chemotherapy is indicated for antitumor and antihormonal effects. Mitotane is a direct adrenolytic, and is the only drug currently available that has extended survival in patients with this disease. Its clinical usefulness is limited by its gastrointestinal and neurological toxicity. Aminoglutethimide inhibits steroid synthesis by blocking the conversion of cholesterol to pregnenolone. It has no antitumor effect in adrenocortical carcinoma, but is effective in relieving the signs and symptoms of excessive hormone production in functioning tumors. Both mitotane and aminoglutethimide have complex mechanisms of action. Their combined use in the treatment of adrenocortical carcinoma requires a complete understanding of their individual actions and awareness of the potential for additive effects, both therapeutic and toxic.     

Influence of polymer architecture on the structure of complexes formed by PEG-tertiary amine methacrylate copolymers and phosphorothioate oligonucleotide.

The influence of polymer structure on the characteristics of complexes of a phosphorothioate antisense oligonucleotide (ISIS 5132) was studied, using well-defined cationic copolymers based on 2-(dimethylamino) ethyl methacrylate (DMAEMA) and poly(ethylene glycol) (PEG). The three related copolymer structures were: DMAEMA-PEG (a diblock copolymer) DMAEMA-OEGMA 7 (a brush-type copolymer), DMAEMA-stat-PEGMA (a comb-type copolymer); each of these were examined together with DMAEMA homopolymer, which served as a control. The results revealed that all the polymers exhibited good binding ability with the oligonucleotide (ON). Interestingly, the comb-type polymer DMAEMA-stat-PEGMA demonstrated the highest binding ability and DMAEMA homopolymer the lowest, as judged by a dye displacement assay. DMAEMA homopolymer produced large agglomerates of smaller individual complexes as observed by optical density, photon correlation spectroscopy and transmission electron microscopy studies. In contrast, two PEG-block copolymers, DMAEMA-PEG and DMAEMA-OEGMA 7, formed compact complexes of 80-150 nm which had good long-term colloidal stability. This is attributed to the steric stabilisation effect of the PEG chains on the ON-copolymer complexes. These two copolymers are believed to form complexes with ON that have a micellar structure. Comb-type DMAEMA-stat-PEGMA copolymer formed highly soluble complexes with the ON that did not phase separate from the buffer solution. This study clearly demonstrates that varying the copolymer architecture allows access to a range of ON complexes. In vitro cytotoxicity experiments on HepG2 cells showed that all of the tertiary amine methacrylate copolymers displayed lower cytotoxicity than the control poly(L-lysine).     

丹参酮ⅡA对神经祖细胞系C17．2的保护作用

目的:了解丹参酮ⅡA对神经祖细胞系C17.2的保护作用,探讨其可能的作用机制。方法:本实验于2005年起在广州血液中心器官移植配型中心实验室进行。C17.2祖细胞系由澳大利亚新南威尔士大学解剖教研室David Walsh博士惠赠。将C17.2细胞以1×109L-1的密度接种,用含10%胎牛血清IMDM,37℃、体积分数为0.05CO2、饱和湿度的CO2培养箱培养,接近融合的C17.2细胞用含0.1mmol/LEDTA的胰酶室温消化,按1∶3的比例传代。C17.2细胞以5×107L-1的密度接种于96孔板或25cm2的培养瓶中,用含10%胎牛血清IMDM培养过夜后,加入含4g/L AAPH(水溶性偶氮引发剂2,2'-偶氮二(2-脒基丙烷)二盐酸盐)无血清的IMDM培养基培养建立神经细胞凋亡模型。C17.2细胞以5×103/孔的密度接种于96孔板中,用含10%胎牛血清IMDM培养过夜后,加入含4g/LAAPH无血清的IMDM培养基培养。对照组不加入丹参酮ⅡA,实验组分别加入0.02,0.05,0.1,0.2mg/L丹参酮ⅡA培养8h,噻唑蓝法检测细胞活性:细胞活性的相对值=(实验组吸光度值/对照组吸光度值)×100%,流式细胞仪检测细胞凋亡。结果:①AAPH处理8h后,C17.2细胞被过氧化损害,大多数细胞失去正常的形态,细胞呈圆形,脱落。加入丹参酮ⅡA后,细胞形态基本保持正常,少数细胞呈圆形。②C17.2细胞在IMDM的培养液中,细胞数量是含4g/L AAPH无血清的IMDM培养基条件下的2.5～3倍。浓度为0.02,0.05,0.1mg/L的丹参酮ⅡA对C17.2细胞有保护作用,质量浓度大于0.2mg/L丹参酮ⅡA对C17.2细胞保护作用降低。③AAPH作用前大部分C17.2细胞的线粒体完整,有少量的早期凋亡细胞和凋亡细胞,AAPH作用后凋亡细胞总数、凋亡细胞明显增加。丹参酮ⅡA处理组可以明显减少早期凋亡细胞。结论:在体外丹参酮ⅡA对神经细胞具有抗凋亡的作用,可以保护神经细胞。     

Memory B Cells that Cross-React with Group 1 and Group 2 Influenza A Viruses Are Abundant in Adult Human Repertoires

1. Download high-res image (291KB)
2. Download full-size image

     

Patterns of Self-reported Behaviour Change Associated with Receiving Voluntary Counselling and Testing in a Longitudinal Study from Manicaland, Zimbabwe

Voluntary counselling and testing (VCT) is promoted as a potential HIV prevention measure. We describe trends in uptake of VCT for HIV, and patterns of subsequent behaviour change associated with receiving VCT in a population-based open cohort in Manicaland, Zimbabwe. The relationship between receipt of VCT and subsequent reported behaviour was analysed using generalized linear models with random effects. At the third survey, 8.6% of participants (1,079/12,533), had previously received VCT. Women who received VCT, both those positive and negative, reduced their reported number of new partners. Among those testing positive, this risk reduction was enhanced with time since testing. Among men, no behavioural risk reduction associated with VCT was observed. Significant increases in consistent condom use, with regular or non-regular partners, following VCT, were not observed. This study suggests that, among women, particularly those who are infected, behavioural risk reduction does occur following VCT.     

Treatment of clinical insulin resistance in children: a systematic review

The objective of this study was to evaluate the effectiveness of interventions aimed at improving clinical insulin resistance and/or pre‐diabetes in children. This study is a systematic review and meta‐analysis. Five electronic databases were searched for randomized controlled trials of at least 2‐months' duration. The outcomes were fasting insulin, homeostasis model assessment of insulin resistance (HOMA‐IR), body mass index (BMI) and adverse outcomes. Four randomized controlled trials were identified. All compared the effect of 6 months of metformin plus or minus lifestyle intervention with placebo plus or minus lifestyle intervention. After pooling results from three trials, the mean difference after 6 months favoured the intervention with a statistically significant mean decrease in fasting insulin, HOMA‐IR and BMI of 9.6 µU mL⁻¹ (95% confidence interval [CI]: 6.3, 13.0 µU mL⁻¹; I² = 76%), 2.7 (95% CI: 1.7, 3.6; I² = 74%) and 1.7 kg m⁻² (95% CI: 1.1, 2.3 kg m⁻²; I² = 75) respectively. Mild gastrointestinal symptoms were reported in 19% (2–29%; median and range) of participants taking metformin. Metformin improves markers of insulin sensitivity and reduces BMI in children and adolescents with clinical insulin resistance or pre‐diabetes. Stronger evidence from high‐quality studies of longer duration and larger sample size are required before clinical conclusions about the optimal treatment protocol in this population can be drawn.