熊果酸磷脂复合物纳米结构脂质载体的制备及其体内药动学研究

目的制备熊果酸磷脂复合物纳米结构脂质载体,并考察其体内药动学。方法乳化?超声分散法制备熊果酸磷脂复合物纳米结构脂质载体,测定粒径、Zeta电位、包封率、载药量、体外释药。大鼠灌胃给药(12.5 mg/mL)后,于0.25、0.75、1、1.5、2、2.5、3、4、6、8、12 h采血,HPLC法测定熊果酸血药浓度,计算主要药动学参数。结果所得制剂呈类球形或球形,平均粒径、Zeta电位、包封率、载药量分别为(209.32±4.47)nm、-(10.82±0.42)mV、80.54%、3.57%;36 h内累积释放度低于70%,释药符合Weibull模型(R2=0.9906)。与原料药、磷脂复合物比较,纳米结构脂质载体tmax延长(P<0.05,P<0.01),Cmax、AUC0~t、AUC0~∞升高(P<0.01);与原料药比较,磷脂复合物、纳米结构脂质载体相对生物利用度分别增加至2.73、3.95倍。结论磷脂复合物纳米结构脂质载体可促进熊果酸体内吸收,提高其口服生物利用度。     

Pseudocontinuous arterial spin labeling reveals dissociable effects of morphine and alcohol on regional cerebral blood flow

We have examined sensitivity and specificity of pseudocontinuous arterial spin labeling (PCASL) to detect global and regional changes in cerebral blood flow (CBF) in response to two different psychoactive drugs. We tested alcohol and morphine in a placebo-controlled, double-blind randomized study in 12 healthy young men. Drugs were administered intravenously. Validated pharmacokinetic protocols achieved minimal intersubject and intrasubject variance in plasma drug concentration. Permutation-based statistical testing of a mixed effect repeated measures model revealed a widespread increase in absolute CBF because of both morphine and alcohol. Conjunction analysis revealed overlapping effects of morphine and alcohol on absolute CBF in the left anterior cingulate, right hippocampus, right insula, and left primary sensorimotor areas. Effects of morphine and alcohol on relative CBF (obtained from z-normalization of absolute CBF maps) were significantly different in the left putamen, left frontoparietal network, cerebellum, and the brainstem. Corroborating previous PET results, our findings suggest that PCASL is a promising tool for central nervous system drug research.     

Fabrication of a Novel Protein Sponge with Dual-Scale Porosity and Mixed Wettability Using a Clean and Versatile Microwave-Based Process

An open-porous protein sponge with mixed wettability is presented made entirely from whey proteins and with promising applications in biomedicine, pharmaceutical, and food industry. The fabrication relies on an additive-free, clean and scalable process consisting of foaming followed by controlled microwave-convection drying. Volumetric heating throughout the matrix induced by microwaves causes fast expansion and elongation of the foam bubbles, retards crust formation and promotes early protein denaturation. These effects counteract collapse and shrinkage typically encountered in convection drying of foams. The interplay of high protein content, tailored gas incorporation and controlled drying result in a dried structure with dual-scale porosity composed of open macroscopic elongated foam bubbles and microscopic pores in the surrounding solid lamellae induced by water evaporation. Due to the insolubility and mixed wettability of the denatured protein network, polar and non-polar liquids are rapidly absorbed into the interconnected capillary system of the sponge without disintegrating. While non-watery liquids penetrate the pores by capillary suction, water diffuses also into the stiff protein matrix, inducing swelling and softening. Consequently, the water-filled soft sponge can be emptied by compression and re-absorbs any wetting liquid into the free capillary space.     

Thomson Pharma数据库使用详解及实例解析

简述Thomson pharma数据库在药物研发各阶段的重要作用、资源体系结构以及主要功能,通过实例分析重点介绍其强大的检索和分析功能,由此引导用户更便捷、更有针对性地使用该数据库。     

Biotechnology financing,not acquisitions,for filling the pharma pipeline – a sustaining strategy

The traditional model of start-up biotechnology companies was to invent, invest, build, partner and make a public offering. This model failed, following an era of investments in far reaching technologies, such as genomics and combinatorial chemistry, that did not yield near term products. In recent times, products that are at or near the clinical stage have again attracted investors to start-up biotechnology companies. After a short period of development, these biotechnology companies are bought by large pharma companies for high prices. If the product fails, the investment is simply written off and there is no backup compound developed, as the biotechnology company with the expertise and the accumulated knowledge of the program and products has been shut down. Most large pharma companies have also downsized exploratory programs. It remains the purview of government and a handful of ‘angel’ investors to fund new ideas. The pharma and biotechnology industry must re-examine this model and build an investment model that retains creativity and the entrepreneurial spirit that allows the time to yield multiple products.     

黑素皮质素受体4基因rs489693位点多态性与慢性精神分裂症患者疗效、BMI及高血糖的关系

目的 探讨黑素皮质素4受体(melanocortin four receptor, MC4R)rs489693多态性对奥氮平治疗后精神分裂症患者临床疗效、BMI、糖脂代谢的影响。方法 选取135例慢性精神分裂症患者,根据DNA测序法检测MC4R基因489693位点的多态性分为AA组19例,AC组46例,CC组55例,于基线、治疗4、8、12周末对所有研究对象行PANSS量表测试,于治疗前和治疗12周末测定研究对象BMI、腰围及血糖、血脂水平,比较3组间各变量的差异。结果 重复测量方差分析发现AA组、AC组、CC组的PANSS各项有时间主效应(P均<0.01）;治疗12周末AA组净增体质量、净增BMI大于AC组(P=0.017,0.031）和CC组(P均<0.01）;净增BMI百分比（%）、血糖（P=0.040）及糖化血红蛋白（P=0.026）AA组均大于CC组(P<0.01）;研究治疗前后3组未见严重不良反应。结论 MC4R基因rs489693的AA基因型可能是奥氮平治疗慢性精神分裂症患者发生肥胖和高血糖的风险因素。     

The sensitivity of human blood platelets to the aggregating agent ADP during different dietary sodium intakes in healthy men

Summary We have investigated the effect of varying sodium intake on the renin-angiotensin system, ADP-induced patelet aggregationin vitro, and blood 5-HT concentrations in 9 male volunteers.Systolic blood pressure was slightly reduced during a low sodium diet, whereas the diastolic pressure remained unchanged. Plasma renin activity and aldosterone concentration both fell significantly when sodium intake was increased; plasma angiotensin lI concentraion also fell, but not significantly.There was a significant fall in haematocrit after an increased sodium intake, but there was no change in the whole-blood platelet count after correcting for this. There were no significant changes in either total (i. e. PRP) or platelet 5-HT concentrations.The extent of platelet aggregation induced by 5 and 20 mol · 1^–1 of ADP increased significantly when dietary sodium intake was increased. When compared with low or normal sodium intakes, lower concentrations of ADP were required to produce 50% of maximum aggregation after a high sodium intake. The 5-HT₂, receptor antagonist ketanserin (1 mol · 1^–1 in vitro) reduced the extent of aggregation induced by 5 mol · 1^–1 ADP after the volunteers had taken a high sodium diet, whereas the angiotensin 11 receptor anatgonist saralasin (1 nmol-1^–1) increased the rate of aggregation after the low sodium diet.Thus, during a high sodium intake, human platelets become more sensitive to the aggregating agent ADP It is possible that this effect is mediatedvia platelet 5-HT₂ receptors, since ketanserin abolished the increase in salt-induced aggregation seen with 5 mol · 1^–1 ADP.     

Science Not Sales: Partnerships and Scientific Exchange With Industry

Parallel to the time that the nurse practitioner (NP) role evolved, pharmaceutical companies recognized the need for more scientific relationships among the academia-based physicians and researchers. The role of the medical science liaison (MSL) was first established by UpJohn in 1967, yet has grown, much like the NP role, to meet the dynamic marketplace changes in health care. To meet the true definition of being a “scientific peer,” backgrounds have become increasingly broad to include clinicians with a PhD, DNP, or physician assistant. The term “clinical practice liaison” (CPL) is used in this article, understanding that the CPL role is the same as the MSL, except that the engagement provider type is almost exclusively NPs and PAs. The CPL is not a sales representative. Rather, the CPL is a field-based professional who is strictly focused on balanced scientific and clinical exchanges.