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991.
Cell-to-cell movement of the Melon Necrotic Spot Virus (MNSV) is controlled by two small proteins working in trans, an RNA-binding protein (p7A) and an integral membrane protein (p7B) separated by an amber stop codon. p7B contains a single hydrophobic region. Membrane integration of this region was observed when inserted into model proteins in the presence of microsomal membranes. Furthermore, we explored the topology and targeting mechanisms of full-length p7B. Here we present evidence that p7B integrates in vitro into the ER membrane cotranslationally and with an Nt-cytoplasmic/Ct-luminal orientation. The observed topology was monitored in vivo by fusing GFP to the Ct of p7B, enabling the overexpression in Escherichia coli cultures. Finally, the topology of a putative p14 movement protein was established by replacing the amber stop codon located between p7A and p7B. 相似文献
992.
Rejniuk VL Schafer TV Ovsep'yan RV Ivnitsky JJ 《Bulletin of experimental biology and medicine》2007,143(6):692-694
Ammonia inhalation (0.84–1.07 mg/liter, 3 h) was accompanied by a 65% increase in ammonia concentration in mixed blood of
intact rats. This treatment did not cause death of intact animals, but potentiated the lethal effect of sodium thiopental
and inhibited external respiration and O2 consumption in animals. The resistance of rats to the lethal effect of barbiturate tended to decrease under conditions of
experimental hyperammonemia induced by intraperitoneal injection of ammonium acetate in a nonlethal dose (6 mmol/kg). Our
results indicate that potentiation of the toxic effect of barbiturates by atmospheric ammonia is related to its resorptive
effects.
__________
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 6, pp. 634–636, June, 2007 相似文献
993.
High throughput ranking of recombinant avian scFv antibody fragments from crude lysates using the Biacore A100 总被引:1,自引:0,他引:1
Leonard P Säfsten P Hearty S McDonnell B Finlay W O'Kennedy R 《Journal of immunological methods》2007,323(2):172-179
Advances in molecular evolution strategies have made it possible to identify antibodies with exquisite specificities and also to fine-tune their biophysical properties for practically any specified application. Depending on the desired function, antibody/antigen interactions can be long-lived or short-lived and, therefore, particular attention is needed when seeking to identify antibodies with specific reaction-rate and affinity properties. Surface plasmon resonance (SPR) biosensors routinely generate sensitive and reliable kinetic data from antibody/antigen interactions for both therapeutic and diagnostic applications. However, many kinetic-based screening assays require rigorous sample preparation and purification prior to analysis. To ameliorate this problem, we developed a rapid and reliable assay for characterising recombinant scFv antibody fragments, directly from crude bacterial lysates. Ninety-six scFv antibodies derived from chickens immunised with C-reactive protein (CRP) were selected by phage display and evaluated using the Biacore A100 protein interaction array system. Antibodies were captured from crude bacterial extracts on the sensor chip surface and ranked based on the percentage of the complex left (% left) after dissociation in buffer. Kinetic rate constants (k(a) and k(d)) and affinity (K(D)) data were obtained for six clones that bound monomeric CRP across a broad affinity range (2.54 x 10(-8) to 3.53 x 10(-10) M). Using this assay format the A100 biosensor yielded high quality kinetic data, permitting the screening of nearly 400 antibody clones per day. 相似文献
994.
Jiali Chen Yuqi Chen Wencong Huang Hanning Wang Yang Du Subin Xiong 《Journal of pharmaceutical sciences》2018,107(9):2366-2376
The objectives of this study were to explore sodium dodecyl sulfate (SDS) and Soluplus on the crystallization inhibition and dissolution of felodipine (FLDP) extrudates by bottom-up and top-down approaches. FLDP extrudates with Soluplus and SDS were prepared by hot melt extrusion, and characterized by polarized light microscopy, differential scanning calorimetry, and fourier transform infrared spectroscopy. Results indicated that Soluplus inhibited FLDP crystallization, and the whole amorphous solid dispersions (ASDs) were binary FLDP-Soluplus (1:3) and ternary FLDP-Soluplus-SDS (1:2:0.15~0.3 and 1:3:0.2~0.4) extrudates. Internal SDS (5%-10%) decreased glass transition temperatures of FLDP-Soluplus-SDS ternary ASDs without presenting molecular interactions with FLDP or Soluplus. The enhanced dissolution rate of binary or ternary Soluplus-rich ASDs in the nonsink condition of 0.05% SDS was achieved. Bottom-up approach indicated that Soluplus was a much stronger crystal inhibitor to the supersaturated FLDP in solutions than SDS. Top-down approach demonstrated that SDS enhanced the dissolution of Soluplus-rich ASDs via wettability and complexation with Soluplus to accelerate the medium uptake and erosion kinetics of extrudates, but induced FLDP recrystallization and resulted in incomplete dissolution of FLDP-rich extrudates. In conclusion, top-down approach is a promising strategy to explore the mechanisms of ASDs' dissolution, and small amount of SDS enhances the dissolution rate of polymer-rich ASDs in the nonsink condition. 相似文献
995.
Joanne Heade Sam Maher Sinead B. Bleiel David J. Brayden 《Journal of pharmaceutical sciences》2018,107(6):1648-1655
In addition to their solubilizing properties, excipients used in lipid-based formulations can improve intestinal permeability of macromolecules. We determined whether admixing of medium-chain fatty acid (MCFA) permeation enhancers with a lipoidal excipient (Labrasol®) could potentiate transepithelial flux of a poorly permeable macromolecule (fluorescein isothiocyanate dextran 4 kDa [FD4]) across rat intestinal mucosae mounted in Ussing chambers. Low concentrations of sodium caprate (C10), sodium undecylenate (C11:1), or sodium laurate (C12) combined with Labrasol® increased the apparent permeability coefficient (Papp) of FD4 to values typically seen with higher concentrations of MCFAs or Labrasol® alone. For example, combination of C11:1 (0.5 mg/mL) with Labrasol® (1 mg/mL) increased the Papp of FD4 by 10- and 11-fold over the respective individual agents at the same concentrations where no enhancement was evident. The increased enhancement ratios seen with the combinations were associated with some perturbation in intestinal histology and with attenuation of an epithelial functional measure, carbachol-stimulated inward short-circuit current. In conclusion, combining three MCFAs separately with Labrasol® increased the Papp of FD4 to values greater than those seen for MCFAs or Labrasol® alone. Ultimately, this may permit lower concentrations of MCFA to be used in combination with other excipients in oral formulations of poorly permeable molecules. 相似文献
996.
摘要:目的 以聚己内酯(PCL)、海藻酸钠、壳聚糖为材料,研制椎间盘双相支架,并评估其作为组织工程椎间盘
的可行性。方法 聚己内酯作为原料,采用熔融电纺法制备取向性多孔纤维环支架,将海藻酸钠/壳聚糖水凝胶注入
到中空的纤维环(AF)支架中央合成双相椎间盘支架。通过体式显微镜、扫描电镜观测双相支架的结构、孔径、孔隙
率;人脐带干细胞复合双相支架体外培养7 d,用死活细胞染色法评价生物相容性,CCK-8实验测定细胞增殖情况,力
学加载仪器测量双相支架的压缩弹性模量。结果 体式显微镜和扫描电镜可见纤维环相成菱形多孔结构,髓核相
(NP)呈不规则多孔结构;纤维环相和髓核相孔径分别为(225.6±3.9)μm、(205.5±5.2)μm,孔隙率分别为(74.17±
0.39)%、(85.52±0.48)%,支架扫描电镜可见细胞黏附在支架表面,周围有细胞外基质分泌;死活细胞染色显示无死
细胞;CCK-8检测结果显示人脐带干细胞具有良好的增殖活性,压缩弹性模量(173.24±44.93)kPa。结论 以聚己内
酯、海藻酸钠、壳聚糖为材料制备的椎间盘双相支架,具有良好的孔径、孔隙率和细胞相容性,支架间结合紧密,具有
三维网络结构,优良的力学特性,是构建组织工程椎间盘理想载体。 相似文献
997.
Chang Liu Zijun Zhou Ju Liu Yang Wang Hongsheng Liu 《Journal of microencapsulation》2018,35(2):115-120
Scavenger receptor class B type 1 (SR-B1) is over-expressed in tumour cells where it mediates the uptake of drug payload of reconstituted high density lipoprotein (rHDL) via the process of reverse cholesterol transport. In this study, rHDL was prepared to determine its function as a drug delivery carrier for targeting hepatocellular carcinoma by incorporating the anti-tumour drug garcinia glycosides (GG) into rHDL to yield rHDL/GG nano-complexes. Structural analysis indicated that the rHDL/GG nano-complex was similar to HDL in size. HepG2 cells treated with fluorescent-labelled rHDL/GG exhibited a time-dependent increase in cell death. Further experiment in which HepG2 cells were treated with rHDL/GG plus plasma-derived HDL showed reduction in cell death compared to treatment with rHDL/GG alone, suggesting that plasma-derived HDL compete with rHDL/GG for binding to the SR-B1 on the cell. We concluded that rHDL could not only incorporate GG but could also serve as a carrier, targeting the drug to HepG2 cells via SR-B1. 相似文献
998.
Regulation of thyroid sodium‐iodide symporter in different stages of goiter: Possible involvement of reactive oxygen species
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Lívia P L Matos Ricardo Cortez Cardoso Penha Luciene C Cardoso‐Weide Mariana L Freitas Diorney L S G Silva Andrea C F Ferreira 《Clinical and experimental pharmacology & physiology》2018,45(4):326-334
Na+/I? symporter (NIS) transports iodide into thyrocytes, a fundamental step for thyroid hormone biosynthesis. Our aim was to evaluate NIS regulation in different status of goitrogenesis and its underlying mechanisms. Wistar rats were treated with methimazole (MMI) for 5 and 21 days, to achieve different status of goiter. We then evaluated the effect of MMI removal for 1 day (R1d), after 5 (R1d‐5d) or 21 (R1d‐21d) days of MMI treatment. MMI increased thyroid weight, iodide uptake and in vitro TPO activity in a time‐dependent way. Although MMI removal evoked a rapid normalization of TPO activity in R1d‐5d, it was still high in R1d‐21d. On the other hand, iodide uptake was rapidly down‐regulated in R1d‐21d, but not in R1d‐5d, suggesting that the increased TPO activity in R1d‐21d led to increased intraglandular organified iodine (I‐X), which is known to inhibit iodide uptake. Since TGFβ has been shown to mediate some effects of I‐X, we evaluated TGFβ and TGFβ receptor mRNA levels, which were increased in R1d‐21d. Moreover, it has been demonstrated that TGFβ stimulates NOX4. Accordingly, our data revealed increased NOX4 expression and H2O2 generation in R1d‐21d. Finally, we evaluated the effect of H2O2 on NIS function and mRNA levels in PCCL3 thyroid cell line, which were reduced. Thus, the present study suggests that there is a relationship between the size of the goiter and NIS regulation and that the mechanism might involve I‐X, TGFβ, NOX4 and increased ROS production. 相似文献
999.
目的:探讨克拉霉素(CLA)与头孢呋辛(CEFU)联合应用对肺炎链球菌和金黄色葡萄球菌的体内抗生素后效应(PAE)。方法:采用琼脂平板倍比稀释法和棋盘法分别测定CLA、CEFU单用及联用时对肺炎链球菌、金黄色葡萄球菌的最小抑菌浓度(MIC),并计算联合指数(FIC);建立小鼠股部肺炎链球菌、金黄色葡萄球菌感染模型,并且应用平板菌落计数法测定CLA与CEFU单用及联合应用对肺炎链球菌、金黄色葡萄球菌的体内PAE。结果:CLA、CEFU单用及联用均对肺炎链球菌、金黄色葡萄球菌产生一定的PAE;两者联用的PAE长于单用时的PAE,呈浓度依赖性,联用后对肺炎链球菌体内PAE表现为相加或无关作用,对金黄色葡萄球菌体内PAE表现为无关作用。结论:CLA与CEFU联用能延长CLA、CEFU单用时的PAE。 相似文献
1000.
目的:制备地塞米松磷酸钠口服液并初步考察其抗大鼠粘连性肠梗阻作用。方法:采用高效液相色谱(HPLC)法测定地塞米松磷酸钠的含量、油水分配系数、考察地塞米松磷酸钠稳定性影响因素;采用裘法祖造模法和试剂盒考察其抗大鼠粘连性肠梗阻的作用。结果:在pH 1.0~8.0范围内,地塞米松磷酸钠的油水分配系数均小于零;pH为8.0时药物降解最慢,抗氧剂Na2SO3和稳定剂丙二醇联用可增加地塞米松磷酸钠的稳定性。与尾静脉注射给药相比,地塞米松磷酸钠口服液能显著降低粘连性肠梗阻(AIO)大鼠肠道丙二醛(MDA)含量(P<0.05),显著提高超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-PX)的活性(P<0.01,P<0.01)。结论:地塞米松磷酸钠口服液具有抗大鼠粘连性肠梗阻作用且其作用强于注射液。 相似文献