Fenofibrate concomitantly decreases serum proprotein convertase subtilisin/kexin type 9 and very‐low‐density lipoprotein particle concentrations in statin‐treated type 2 diabetic patients

Aim: Diabetic dyslipidaemia, characterized by hypertriglyceridaemia as a result of elevated serum very‐low‐density lipoprotein (VLDL) concentrations, contributes to the increased risk of cardiovascular disease (CVD) in type 2 diabetes (T2DM). Proprotein convertase subtilisin/kexin type 9 (PCSK9) may play a role in regulating VLDL metabolism. We investigated the effect of fenofibrate on serum PCSK9 and VLDL particle concentrations in T2DM patients already receiving statin therapy. Methods: In a double‐blind randomized crossover study, 15 statin‐treated T2DM patients (63 ± 8 years, body mass index (BMI) 29 ± 3 kg/m²) were treated with fenofibrate (145 mg/day) or matching placebo for 12 weeks. Serum PCSK9 concentrations were measured by immunoassay. VLDL particle concentration and size were determined by nuclear magnetic resonance spectroscopy. Results: Fenofibrate decreased serum triglycerides (?23%), VLDL‐triglycerides (?51%), total cholesterol (?11%), LDL‐cholesterol (?16%), apolipoprotein B‐100 (?16%), apolipoprotein C‐III (?20%) and PCSK9 (?13%) concentrations compared with placebo (p < 0.05). Fenofibrate also decreased serum concentrations of large (?45%), medium (?66%) and small VLDL (?67%) particles (p < 0.05), without altering VLDL particle size. Serum PCSK9 reduction correlated with decreases in total (r = 0.526, p = 0.044) and small (r = 0.629, p = 0.021) VLDL particle concentrations. Conclusions: Fenofibrate concomitantly decreased serum PCSK9 and VLDL particle concentrations in statin‐treated T2DM patients. These findings support a mechanistic link between PCSK9 and VLDL metabolism, possibly through an effect of PSK9 on VLDL receptor degradation.     

Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib

Background

Dasatinib 100 mg once daily achieves intermittent BCR-ABL kinase inhibition and is approved for chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib. To better assess durability of response to and tolerability of dasatinib, data from a 2-year minimum follow-up for a dose-optimization study in chronic-phase chronic myeloid leukemia are reported here.

Design and Methods

In a phase 3 study, 670 chronic-phase chronic myeloid leukemia patients with resistance, intolerance, or suboptimal response to imatinib were randomized to dasatinib 100 mg once-daily, 50 mg twice-daily, 140 mg once-daily, or 70 mg twice-daily.

Results

Data from a 2-year minimum follow-up demonstrate that dasatinib 100 mg once daily achieves major cytogenetic response and complete cytogenetic response rates comparable to those in the other treatment arms, and reduces the frequency of key side effects. Comparable 2-year progression-free survival and overall survival rates were observed (80% and 91%, respectively, for 100 mg once daily, and 75%–76% and 88%–94%, respectively, in other arms). Complete cytogenetic responses were achieved rapidly, typically by 6 months. In patients treated with dasatinib 100 mg once daily for 6 months without complete cytogenetic response, the likelihood of achieving such a response by 2 years was 50% for patients who had achieved a partial cytogenetic response, and only 8% or less for patients with minor, minimal, or no cytogenetic response. Less than 3% of patients suffered disease transformation to accelerated or blast phase.

Conclusions

Intermittent kinase inhibition can achieve rapid and durable responses, indistinguishable from those achieved with more continuous inhibition.     

银甲丹治疗阴虚火旺型甲亢

目的:对银甲丹治疗甲亢(Graves’病)阴虚火旺型患者的临床疗效观察。方法:将符合西医诊断Graves’病,又符合中医"阴虚火旺证"患者共54例,随机分为银甲丹组和单用西药组,进行了3个月的疗效观察。对治疗前后临床症状、体征、血清甲状腺激素、甲状腺相关抗体及细胞因子等进行比较分析。结果:银甲丹组在改善患者临床症状、体征及异常的甲状腺激素水平等方面优于单用西药组(其中甲状腺肿大方面银甲丹组近43%患者治疗后恢复正常,激素水平呈明显下降接近正常水平)。结论:银甲丹组治疗甲亢临床疗效优于单用西药组。     

论西部大开发背景下的新疆高等医学教育

新疆作为向西开放的前沿,其特殊的历史地位、现实作用和区域特色都将在西部大开发战略中发挥举足轻重的影响。探讨新疆高等医学教育改革与发展的总体思路,更好地发挥教育资源的作用,大量培养西部建设需要的、适应性强的复合型和实用型医学人才是我们面临的又必须解决的一个重大课题。     

MOAP方案治疗急性淋巴细胞白血病疗效观察

目的观察MOAP方案治疗急性淋巴细胞白血病（ALL）的近期疗效和不良反应。方法我科于2003年1月-2008年12月应用MOAP方案治疗30例ALL,对照组用TOLP方案,2个疗程评价化疗方案的疗效,同时记录不良反应。结果MOAP组治疗初治ALL缓解率90.9%,对照组86.2%。MOAP组达到缓解的时间（15.7±6.4）d,对照组（19.8±3.2）d。MOAP组感染率、药物不良反应均低于对照组。结论MOAP方案治疗ALL有良好的疗效,且耐受性好。     

Application of computational toxicological approaches in human health risk assessment. I. A tiered surrogate approach

Hazard identification and dose–response assessment for chemicals of concern found in various environmental media are typically based on epidemiological and/or animal toxicity data. However, human health risk assessments are often requested for many compounds found at contaminated sites throughout the US that have limited or no available toxicity information from either humans or animals. To address this issue, recent efforts have focused on expanding the use of structure–activity relationships (SAR) approaches to identify appropriate surrogates and/or predict toxicological phenotype(s) and associated adverse effect levels. A tiered surrogate approach (i.e., decision tree) based on three main types of surrogates (structural, metabolic, and toxicity-like) has been developed. To select the final surrogate chemical and its surrogate toxicity value(s), a weight-of-evidence approach based on the proposed decision tree is applied. In addition, a case study with actual toxicity data serves as the evaluation to support our tiered surrogate approach. Future work will include case studies demonstrating the utility of the surrogate approach under different scenarios for data-poor chemicals. In conclusion, our surrogate approach provides a reasonable starting point for identifying potential toxic effects, target organs, and/or modes-of-action, and for selecting surrogate chemicals from which to derive either reference or risk values.