Polymeric genes MEL8, MEL9 and MEL10 — new members of α-galactosidase gene family in Saccharomyces cerevisiae

Summary We used a combination of genetic hybridization analysis and electrokaryotyping with radioactively labelled MEL1 gene probe hybridization to isolate and identify seven polymeric genes for the fermentation of melibiose in strain CBS 5378 of Saccharomyces cerevisiae (syn. norbensis). Four of the MEL genes, i.e. MEL3, MEL4, MEL6 and MEL7, were allelic to those found in S. cerevisiae strain CBS 4411 (syn. S. oleaginosus) whereas three genes, i.e. MEL8, MEL9 and MEL10 occupied new loci. Electrokaryotyping showed that all seven MEL genes in CBS 5378 were located on different chromosomes. The new MEL8, MEL9 and MEL10 genes were found on chromosomes XV, X/XIV and XII, respectively.     

采用微孔聚丙烯纤维材料的“四川联大Ⅰ型”管外流式(ELF)中空纤维膜式氧合器的研制

介绍了“四川联大Ⅰ型”（以下简称：ＳＵＵⅠ）管外流式（ＥＬＦ）中空纤维膜式氧合器的研制、设计、外形制做及离心封端等过程，重点介绍了中空纤维膜材料选择，膜肺离心封端的原理、材料、设备及方法，并对聚氨酯胶进行离心封端的具体步聚作了较详细的叙述。作者根据自身在国外与国内的研制经验，认为离心封端的关键在于：（１）中空纤维膜材料的质量及成束质量；（２）聚氨酯封端胶材料固化特性的掌握及料量计算；（３）反应温度控制；（４）气体排除；（５）转速的控制；（６）纤维束的安装；（７）脱模和切头的时间掌握等方面。作者用外购的材料和自己设计制造的离心封端机成功地制造了我国第一个管外流式（ＥＬＦ）中空纤维成人氧合器。ＳＵＵⅠ膜式氧合器的设计是作者在国外建立的交叉流式膜肺Ｏ２、ＣＯ２传递模型的具体应用。     

透析法去除红细胞渗透性低温保护剂的实验研究

要实现人类红细胞深低温保存,必须在冷冻前添加、复温后去除低温保护剂.本研究提出了低温保护剂的新型的透析去除法,与常规的离心洗涤法比较而言,该方法能够快速、有效、安全地去除红细胞内的低温保护剂(甘油).使用该方法冰冻.复温.洗涤后的红细胞计数回收率为(89.17±2.46)%,血红蛋白回收率为(84.93±4.64)%,上清游离血红蛋白的含量为(0.66 ±0.13)g/L,所得冰冻-复温-洗涤后的红细胞悬液的渗透压(残余甘油的含量)为(340.33±20.56)mOsm,均达到了国家对冰冻洗涤红细胞的质量标准要求.     

Enhancement of O2 and CO2 Transfer Through Microporous Hollow Fibers by Pressure Cycling

An intravascular gas exchange device for the treatment of respiratory failure consisted of a multitude of blind-ended hollow fibers glued in a pine-needle arrangement to a central gas supply catheter. It has previously been shown that gas desorption rates can be significantly enhanced by cycling gas pressure between a hypobaric level of 130 and an ambient level of 775 Torr. In this study, influences of the cycling frequency (f) and the cycle fraction during which hypobaric pressure is applied () were investigated. Rates of O₂ desorption from O₂-saturated water and CO₂ desorption from CO₂-saturated water into a manifold containing 198 fibers, 380 m in diameter, were measured over a range of f from 0.2 to 1.0 Hz, from 0.1 to 0.8, and fiber lengths from 4 to 16 cm. Relative to operation at ambient pressure, pressure cycling increased O₂ transfer 3–4 times and CO₂ transfer 4–6 times when the water flowed over the fiber manifold at 2.3 l/min. Transfer rates were relatively insensitive to f and with 80–90% of maximum enhancement obtained when was as low as 0.2. Transfer rates increased continuously with fiber length, implying that pressure cycling reduced the intra-fiber resistance to gas diffusion. A mathematical diffusion model which utilized only two adjustable parameters, a mass transfer coefficient for O₂ and for CO₂, simulated the trends exhibited by desorption data. © 1998 Biomedical Engineering Society. PAC98: 8745Hw, 8790+y     

Surface Modification of Poly(lactide-co-glycolide) Nanospheres by Biodegradable Poly(lactide)-Poly(ethylene glycol) Copolymers

The modification of surface properties of biodegradable poly(lactide-co-glycolide) (PLGA) and model polystyrene nanospheres by poly(lactide)-poly(ethlene glycol) (PLA:PEG) copolymers has been assessed using a range of in vitro characterization methods followed by in vivo studies of the nanospheres biodistribution after intravenous injection into rats. Coating polymers with PLA:PEG ratio of 2:5 and 3:4 (PEG chains of 5000 and 2000 Da, respectively) were studied. The results reveal the formation of a PLA: PEG coating layer on the particle surface resulting in an increase in the surface hydrophilicity and decrease in the surface charge of the nanospheres. The effects of addition of electrolyte and changes in pH on stability of the nanosphere dispersions confirm that uncoated particles are electrostatically stabilized, while in the presence of the copolymers, steric repulsions are responsible for the stability. The PLA:PEG coating also prevented albumin adsorption onto the colloid surface. The evidence that this effect was observed for the PLA:PEG 3:4 coated nanospheres may indicate that a poly(ethylene glycol) chain of 2000 Da can provide an effective repulsive barrier to albumin adsorption. The in vivo results reveal that coating of PLGA nanospheres with PLA:PEG copolymers can alter the biodistribution in comparison to uncoated PLGA nanospheres. Coating of the model polystyrene nanospheres with PLA:PEG copolymers resulted in an initial high circulation level, but after 3 hours the organ deposition data showed values similar to uncoated polystyrene spheres. The difference in the biological behaviour of coated PLGA and polystyrene nanospheres may suggest a different stability of the adsorbed layers on these two systems. A similar biodistribution pattern of PLA:PEG 3:4 to PEG 2:5 coated particles may indicate that poly(ethylene glycol) chains in the range of 2000 to 5000 can produce a comparable effect on in vivo behaviour.     

湿法纺制PEI／PES中空纤维气体分离共混膜

采用湿法纺丝工艺纺制了聚醚酰亚胺（ＰＥＩ）－聚苯醚砜（ＰＥＳ）中空纤维Ｈ２－Ｎ２和Ｈｅ－Ｎ２分离共混膜,得到Ｈ２和Ｈｅ的渗透通量及选择性为：ＪＨ２＝３６０ＧＰＵ,αＨ２／Ｎ２＝１６２,ＪＨｅ＝１８１ＧＰＵ,αＨｅ／Ｎ２＝７６．７;研究了芯液组成及其流量对膜性能的影响。通过扫描电镜,分析了中空纤维膜的结构,讨论了膜制备过程中的相转化原理。     

应力场下固—液相分离制备微孔聚丙烯中空纤维膜

将聚丙烯和石蜡油的混合物熔融挤出,使之在较高的应力场下冷却和相分离,得到了弹性聚丙烯中空纤维。这种部分结晶的弹性纤维可能具有平行排列的片晶结构,石蜡油存在于片晶之间。将石蜡油提取掉后稍加拉伸即可得到透气性很好的微孔中空纤维渗透膜。     

胰岛素中空栓剂的制备及兔体药效实验

 目的研究胰岛素中空栓剂的制备及对正常家兔的降糖效果。方法用普通栓剂模具制备，以半合成脂肪酸酯为基质，以甘油为溶剂，月桂氮-酮为吸收促进剂，每枚栓剂含胰岛素4u，对其融变时限、含量等进行测定；将中空栓剂置于家兔直肠内，用酶-苯酚法测定家兔血糖，并与皮下注射进行比较。结果融变时限符合药典要求，含量为4u，胰岛素中空栓剂的降糖效果与皮下注射胰岛素1u相当。结论胰岛素中空栓剂有较好的吸收，可能成为胰岛素非注射给药的有效载体。     

HPLC法测定水飞蓟宾脂质纳米粒在小鼠肝脏中的药物浓度

目的:建立水飞蓟宾脂质纳米粒在小鼠肝脏中药物浓度的高效液相色谱测定方法。方法:小鼠肝脏匀浆液在 pH 8.2条件下用乙醚提取,氮气吹干,残渣以流动相溶解后进样。采用 Nova-pak C_(18)色谱柱(3.9 mm × 150 mm,4 μm),以甲醇-0.05mol·L~(-1)磷酸二氢钾(10:11,磷酸调至pH 4.0)为流动相,流速 1.0 mL·min~(-1),检测波长为288 nm,内标为a-萘酚。结果:水飞蓟宾的线性范围为1.60～31.8 μg·g~(-1)(r=0.999 4);S/N=3时,最低检测限为10 ng;高、中、低3个浓度的平均回收率为100.8％～104.7％,日内 RSD为 1.6％～3.3％,日间 RSD为 3.2％～4.8％,n=5。结论:所建方法灵敏、准确,适用于水飞蓟宾肝靶向制剂的肝脏药物浓度测定及肝脏靶向性评价。     

Study and development of encapsulated forms of 4, 5′, 8‐Trimethylpsoralen for topical drug delivery

Trimethylpsoralen (TMP) is often used to treat skin diseases (i.e., psoriasis, vitiligo, etc.). This drug permeates moderately the skin barrier. In the present study, we investigated the effect of formulation on the improvement of TMP skin bioavailability. Three formulations were performed. Each form (liposomes, nanospheres, and EtOH solution) contained 0.05% of TMP. For each preparation, the quantity deposited on the skin surface was 250 µg (Q₀). The TMP percutaneous penetration through ex‐vivo human skin was processed by Franz^® cells (n=4) using a human albumin solution (1.4% w/v) as receiver medium. The percentages of the extracted TMP that permeated through the skin and that were retained in the skin over 24 h, were calculated with respect to Q₀. The values obtained were reported, respectively, as follows: EtOH solution (1.33 vs. 0.08%), liposomes (0.93 vs. 0.93%), and PLG‐nanospheres (0.79 vs. 3.01%). So, considering the correlation between the cumulated amounts of TMP permeated through the skin and the TMP stocked in the skin, the nanosphere form showed the higher quantity of TMP accumulated in the skin structures. On the other hand, the maximum value of the flux (ng/cm²/h) in the steady state of TMP incorporated in each formulation was at 6 h for all formulations: 173.5±1.06 (EtOH solution) > 120.4±1.06 (liposomes) > 93.82±0.88 (PLG‐nanospheres). These results indicate that the controlled release of TMP by incorporation in PLG‐nanospheres may increase drug content in the skin, while maintaining a minimal percutaneous absorption. Finally, this work shows that the PLG‐nanospheres could constitute a promising approach for controlling TMP release in order to maintain its topical activity. Drug Dev. Res. 61:86–94, 2004. © 2004 Wiley‐Liss, Inc.