Pharmacokinetics of sifuvirtide, a novel anti-HIV-1 peptide, in monkeys and its inhibitory concentration in vitro

Aim: To study the pharmacokinetics of sifuvirtide, a novel anti-human immunodeficiency virus (HIV) peptide, in monkeys and to compare the inhibitory concentrations of sifuvirtide and enfuvirtide on HIV-1-infected-cell fusion. Methods: Monkeys received 1.2 mg/kg iv or sc of sifuvirtide. An on-line solid-phase extraction procedure combined with liquid chromatography tandem mass spectrometry (SPELC/MS/MS) was established and applied to determine the concentration of sifuvirtide in monkey plasma. A four-I-127 iodinated peptide was used as an internal standard. Fifty percent inhibitory concentration (IC50) of sifuvirtide on cell fusion was determined by co-cultivation assay. Results: The assay was validated with good precision and accuracy. The calibration curve for sifuvirtide in plasma was linear over a range of 4.88-5000 mu g/L, with correlation coefficients above 0.9923. After iv or sc administration, the observed peak concentrations of sifuvirtide were 10626 +/- 2886 mu g/L and 528 +/- 191 mu g/L, and the terminal elimination half-lives (T,12) were 6.3 +/- 0.9 h and 5.5 +/- 1.0 h, respectively. After sc, T-max was 0.25-2 h, and the absolute bioavailability was 49% +/- 13%. Sifuvirtide inhibited the syncytium formation between HIV-1 chronically infected cells and uninfected cells with an IC50 of 0.33 mu g/L. Conclusion: An on-line SPE-LC/MS/MS approach was established for peptide pharmacokinetic studies. Sifuvirtide was rapidly absorbed subcutaneously into the blood circulation. The T-1/2 of sifuvirtide was remarkably longer than that of its analog, enfuvirtide, reported in healthy monkeys and it conferred a long-term plasma concentration level which was higher than its IC50 in vitro.

眼镜蛇毒神经生长因子对成年猫坐骨神经损伤后的作用

目的　探讨从眼镜蛇毒分离纯化出的神经生长因子(nerve grow th facto r, N GF) 对成年猫坐骨神经 损伤后的影响。方法　制成成年猫坐骨神经损伤模型, 损伤局部注射蛇毒N GF 2 Lgö(kg·d) , 分别治疗10 d 和30 d, 并与对照组(损伤坐骨神经, 不给药物) 比较。结果　术后10 d, 对照组术侧远端神经纤维数量比治疗组明显减少 (P < 0. 01) , 治疗组术侧足底刺激出现早, 肢体活动恢复快。术后30 d, 治疗组术侧远端神经纤维大量再生, 再生神 经纤维数量已明显超过对照组和术后10 d 组水平(P < 0. 01) , 但结构紊乱, 轴突和郎氏结消失。术侧肢体在连续注 射N GF 16 d 左右出现足底刺激反应消失, 肢体瘫痪等改变。结论　眼镜蛇毒N GF 在神经损伤早期应用能减轻神 经纤维发生的溃变, 促进受损神经的再生与功能恢复; 而损伤局部长时间注射蛇毒N GF 则会导致神经纤维增生过 度, 丧失传导功能。

鸡胚背根神经节培养法测定神经生长因子(NGF) 活性的条件优化

目的　探索一套稳定可靠的鸡胚背根神经节测定N GF 活性的实验条件。　方法　通过观察培养 基、鸡血浆和鸡胚浸液的比例、背根神经节部位、培养时间等条件对N GF 刺激神经节生长的影响, 从而 建立一套该培养法检测N GF 活性的优化条件。　结果　以DM EM 为母液, 在含20% 鸡血浆和15% 鸡胚 浸液的培养基中, 利用伊莎褐鸡胚腰椎背根神经节, 在终浓度为30 ngöm l 的蛇毒N GF 的刺激下, 培养36h 可以得到较好的实验结果。　结论　该条件简单实用、分辨率高、重复性好。

New evidence for the origin and behaviour of deep ocean 'crusts'

In situ tests in deep waterWest African clays show crust-like shear strengths within the top few metres of sediment. Typical strength profiles show su rising from mud-line to 10 kPa to 15 kPa before dropping back to normally consolidated strengths of 3 kPa to 4 kPa by 1.5m to 2m depth. A Cam-shear device is used to better understand the mechanical behaviour of undisturbed crust samples under pipelines. Extremely variable peak and residual shear strengths are observed for a range of pipeline consolidation stresses and test shear rates, with residual strengths approximating zero. ESEM of undisturbed samples and wet-sieved samples from various core depths show the presence of numerous randomly-located groups of invertebrate faecal pellets. It is therefore proposed that the cause of strength variability during shear testing and, indeed, of the crust's origin, is the presence of random groups of faecal pellets within the sediment. © 2011 Taylor & Francis Group, London.

Gamma-ray spectroscopy at TRIUMF-ISAC

The 8π spectrometer at TRIUMF-ISAC consists of 20 Compton-suppressed germanium detectors and various auxiliary devices. The Ge array, once used for studies of nuclei at high angular momentum, has been transformed into the world's most powerful device dedicated to radioactive-decay studies. Many improvements in the spectrometer have been made, including a high-throughput data acquisition system, installation of a moving tape collector, incorporation of an array of 20 plastic scintillators for β-particle tagging, 5 Si(Li) detectors for conversion electrons, and 10 BaF2 detectors for fast-lifetime measurements. Experiments can be performed where data from all detectors are collected simultaneously, resulting in a very detailed view of the nucleus through radioactive decay. A number of experimental programmes have been launched that take advantage of the versatility of the spectrometer, and the intense beams available at TRIUMF-ISAC. © 2006 American Institute of Physics.

High-resolution γ-ray spectroscopy: A versatile tool for nuclear β-decay studies at TRIUMF-ISAC

High-resolution γ-ray spectroscopy is essential to fully exploit the unique, high-quality beams available at the next generation of radioactive ion beam facilities such as the TRIUMF isotope separator and accelerator (ISAC). The 8π spectrometer, which consists of 20 Compton-suppressed HPGe detectors, has recently been reconfigured for a vigorous research programme in weak interaction and nuclear structure physics. With the addition of a variety of ancillary detectors it has become the world's most powerful device dedicated to β-decay studies. This paper provides a brief overview of the apparatus and highlights from recent experiments. © 2005 IOP Publishing Ltd.

武汉东湖甲藻水华与环境因子的关系

由于水体富营养化等原因,在全球范围内,水华频繁爆发.近来,发现武汉东湖出现了一种拟多甲藻(Peridiniopsis sp.)水华,该藻是广温性种,水华持续时间较长,最高细胞密度达2541.44×10~4cells/L.研究了武汉东湖拟多甲藻水华种群动态及其与环境因子之间的关系.相关分析表明,拟多甲藻密度和表层总磷、1.2m处的总氮以及表层硝酸盐浓度成显著正相关,但是总磷、溶解性磷酸盐、总氮、磷酸盐以及氨氮浓度在形成明显水华前大幅度升高,水华消亡时,处于低谷.适合的光照条件,也是拟多甲藻水华形成的刺激因子

香溪河官庄坪库湾叶绿素a及初级生产力的分布特征

2005年2月—4月对三峡库区香溪河进行了定点初级生产力及相关影响因子的研究,分析了官庄坪库湾叶绿素a含量和初级生产力的时空分布特征。结果表明,叶绿素a含量、初级生产力在各水层的变化具有相同的周期性,均存在5个峰值,平均每个周期为7—10d左右,但两者不同步。官庄坪测站的真光层深度为10m左右,介于湖泊与海洋之间,光补偿点为4—5m。初级生产力最大值出现在水下0.5m处,并沿物理深度逐渐降低;叶绿素a含量最大值则出现在水下2m处。水温的垂直变化在后期差异明显,各水层日平均水温增量(ΔT/d)与平均毛初级生

五里湖深水区沉水植被重建策略探索

本文以菹草(PotamogetoncrispusL.)和伊乐藻(Elodeanuttallii)为材料,在不同水深条件下对沉水植物的生长进行了研究。结果表明:随着水深的增加,菹草和伊乐藻的茎伸长速度逐渐增大,但分支数或株数减少,最终植物生物量减少;菹草和伊乐藻种群能够建立的水深极限条件分别为:2倍SD和2.3倍SD。在冬季透明度为1.1-1.2m条件下,伊乐藻种群在2.5m水深处成功建立。高透明度(>1.1m)是五里湖深水区伊乐藻种群建立的关键条件。在此研究的基础上,本文探讨了重建五里湖深水区沉水植被的可

两种改善富营养化湖泊水质的生物膜技术比较

用三个长宽高各为1.0m×1.0m×1.2m的水缸,装15cm的底泥和85cm的富营养化污水,来模拟水/底泥系统。分别在两个水缸中布设软性填料和自制人工水草来改善水质,另一水缸做空白对照。结果表明:在同投影面积下,布设人工水草比布设软性填料提高水体透明度的速度快;布设软性填料和人工水草在第36d时,CODMn分别降低89.63%、92.90%;TN分别降低93.45%、94.97%;NH3-N分别降低65.10%、70.15%;两者对TP都有一定影响。总体效果而言,人工水草处理效果优于软性填料。