Albumin microspheres as carriers for the antiarthritic drug celecoxib

The present study investigates the preparation of celecoxib-loaded albumin microspheres and the biodistribution of technetium-99m (^99mTc)-labeled celecoxib as well as its microspheres after intravenous administration. Microspheres were prepared using a natural polymer BSA using emulsification chemical cross-linking method. The prepared microspheres were characterized for entrapment efficiency, particle size, and in vitro drug release. Surface morphology was studied by scanning electron microscopy. Biodistribution studies were performed by radiolabeling celecoxib (CS) and its microspheres (CMS) using^99mTc and injecting arthritic rats intravenously. The geometric mean diameter of the microspheres was found to be 5.46 μm. In vitro release studies indicated that the microspheres sustained the release of the drug for }6 days. Radioactivity measured in different organs after intravenous administration of celecoxib solution showed a significant amount of radioactivity in the liver and spleen. In case of celecoxib-loaded microspheres, a significant amount of radioactivity accumulated in the lungs. No significant difference (P>.1) in the radioactivity was observed between the inflamed joint and the noninflamed joint following intravenous injection of^99mTc-CS. However, in case of the microspheres (CMS), the radioactivity present in the inflamed joint was 2.5-fold higher than in the noninflamed joint. The blood kinetic studies revealed that celecoxib-loaded albumin microspheres exhibited prolonged circulation than the celecoxib solution.     

Rate transition and regulatory coupling in endocytosis of interferon-alpha and tumor necrosis factor-alpha in human epithelial tumor cells.

The time-dependent concentrations of interferon-alpha and tumor necrosis factor-alpha associated with the membrane and internalized by cells contain information on the kinetics of endocytosis and their cellular processing. This information can be reduced quantitatively by application of the respective compartmental models. In our studies of human epithelial tumor cells interacting with human interferon-alpha and human tumor necrosis factor-alpha, we accounted only for actual endocytosis and elimination of the tracer from cells by a novel method sensitive to changes in the rate of endocytosis, to the delay in tracer elimination, and to the nonlinear regulatory coupling between endocytosis and the internalized ligand. Data reduced by this method resulted in best-fit parameter values statistically superior to values obtained by previous methods (Bajzer et al., 1989). The results indicate a change with time in the rate of endocytosis of tumor necrosis factor-alpha and the inhibition of endocytosis by the endocytosed ligand-receptor complex. We conclude that sorting and processing of interferon-alpha and tumor necrosis factor-alpha are restricted by the type of both the receptor and the cell.     

法夫酵母分批发酵虾青素动力学研究

通过三联30L全自动发酵罐对虾青素产生菌法夫酵母的分批发酵动力学进行了研究,结果表明,法夫酵母的生长与限制性基质葡萄糖浓度之间符合Logistic方程,建立了细胞生长、产物合成和基质消耗随时间变化的数学模型。应用MATLAB软件对发酵动力学模型进行最优参数估计和非线性拟和,获得最大比生长速率（umax）和产物得率（Yp/x）分别为0.1829/h、0.1524g/g,虾青素分批发酵中细胞生长与产物合成属于偶联型,模型模拟计算结果和实验值能较好地吻合,动力学研究结果表明该模型能较好地反映细胞的生长、底物消耗和产物合成过程机制。     

Effect of heating temperature and time on pharmaceutical characteristics of albumin microspheres containing 5-fluorouracil

Conclusion  In this study, we found that both heating temperature and heating time affect mean particle size, particle size distribution, and drug entrapment efficiency of albumin microspheres. The change in heating temperature may affect the particle size of the product, especially when heating is carried out at a lower temperature (90°C–120°C). Hence the temperature should be selected on the basis of desired size range. Given that it is desirable for a maximum amount of the drug used in the preparation to become entrapped in microspheres, heating temperature and heating time for denaturation of albumin should be selected cautiously, as both have a significant effect on drug entrapment efficiency. In the present case, the highest entrapment was found in batches prepared by heating at 90°C for 5 minutes. However, the extent of stabilization at the selected temperature and the time of heating should also be taken into consideration, as they may affect the release of drugs to target tissue.     

Estimation of Kinetic Parameters for Bioremediation of Cr(VI) from Wastewater Using Pseudomonas taiwanensis,an Isolated Strain from Enriched Mixed Culture

An aerobic mixed culture collected in the form of activated sludge was enriched for Cr(VI) reduction. An indigenous microorganism was isolated from the enriched aerobic mixed culture and identified as Pseudomonas taiwanensis. Bioremediation studies were carried out for treating Cr(VI)-contaminated wastewater using the indigenous microorganism. The kinetic studies were carried out for initial Cr(VI) concentrations ranging from 20 to 200 mg L^?1. The maximum consumption of Cr(VI) obtained was 108.3 mg L^?1 for an initial Cr(VI) concentration of 150 mg L^?1 at a solution pH of 7.0. The effect of nutrient dosage and pH were studied to get their optimum values. The same isolated bacterial strain was also used to treat Cr(VI)-contaminated industrial wastewater collected from a local plating industry. Various growth kinetic models, such as Monod, Powell, Haldane, Luong, and Edward models, were fitted with the obtained experimental data. The obtained results for different growth kinetic models indicate that the growth kinetics of Pseudomonas taiwanensis for bioremediation of Cr(VI) can be better understood by the Luong model (R² = .913). The rate kinetic analysis was performed using zero-order and three-half-order kinetic models. The three-half-order kinetic model was found to be suitable for the present bioremediation study.     

Do collagenases unwind triple‐helical collagen before peptide bond hydrolysis? Reinterpreting experimental observations with mathematical models

It has been postulated that triple-helical collagen is actively unwound by collagenases before peptide bond hydrolysis--a supposition that explains the small catalytic rate constant associated with collagenolysis. We propose an alternate model of collagen degradation that does not require active unwinding by collagenases, but instead suggests that the regions of collagen near the collagenase cleavage site can adopt either a native triple-helical or a partially unfolded conformation. In this model, collagenases preferentially bind to and stabilize partially unfolded conformers before cleaving the scissile bond. Existing experimental observations (which were previously taken to support active unwinding models) are reinterpreted using corroborative evidence from numerical simulations and found to be consistent with this framework. These data support the notion that collagen, like all other biological heteropolymers, undergoes thermal fluctuations that cause it to sample distinct structures in the neighborhood of the native state, and collagenolysis occurs when collagenases recognize the appropriate unwound conformers.     

细胞生理代谢网络模型重构和优化的进展

细胞中自发或由酶催化的代谢反应组成了高度复杂的代谢网络,其与细胞生理代谢活动运作密切相关。细胞生理代谢网络模型的重构有助于从系统层面上解析基因型与生长表型之间的关联,为细胞生理代谢活动精准刻画与生物绿色制造等研究提供重要的计算生物学工具。本文系统介绍了全基因组尺度代谢网络模型(genome-scale metabolic models, GEMs)、动力学模型、酶约束代谢模型(enzyme-constrained genome-scale metabolic models, ecGEMs)等不同类型细胞生理代谢网络模型发展与应用的最新研究进展;同时还介绍了GEMs自动化构建研究进展以及条件特异性GEMs建模策略。人工智能技术为高精度细胞生理代谢网络模型构建提供了全新机遇,本文进一步总结了人工智能技术在动力学模型和酶约束模型构建等领域的应用。各类细胞生理代谢网络模型的高质量重构将为今后的定量合成生物学与系统生物学等研究提供强大计算支撑。     

Effects of Sterilization and Temperature on the Decrease Kinetic of Lead Bioavailability in Two Different Soil Groups

Sorption of metal ions by soil and clay minerals is a complex process involving different mechanisms, and controlled by different variables that can interact. The impacts of sterilization and incubation temperature on the decrease kinetic of Pb bioavailability in two different groups of soils were studied. Surface soils were sampled from Guilan and Hamadan provinces in the north and northwest of Iran with temperate and semiarid climates. The decrease kinetic of Pb bioavailability in the Pb(NO₃)₂ treated (400 μg Pb g^?1) soils has been studied in solid state incubation in sterile and unsterile conditions at 15, 27 and 37°C. The decrease of DTPA-extractable Pb in both groups of soils is often characterized by an initial rapid step followed by a slow step. The temperate soil with high affinity surface sites for Pb sorption compared to semiarid soils had a lower DTPA-extractable Pb in each time of extraction. Sterilization and soil incubation at lower temperature decreased the rate of Pb sorption/precipitation processes. Among the kinetic models the second order model and Elovich kinetic equation were the better choice to express the decrease kinetic of Pb bioavailability according to higher determined coefficient and the small standard error of the estimate. The determination coefficients of the mass transfer equation were increased and the standard errors of the estimates were decreased in sterile and unsterile conditions by increasing incubation temperature from 15 to 37°C.     

耐高温酵母乙醇间歇发酵动力学研究

该研究采用耐高温型酵母,在不同葡萄糖浓度(5%~30%wt)下进行了乙醇间歇发酵的动力学研究,确定了适合该酵母的最佳底物浓度范围为16%~20%(wt)。同时选取合适的动力学模型,通过实验数据的非线性性拟合,得出了不同底物浓度下对应的动力学参数值,并分析了各动力学参数值随底物浓度增加而变化的趋势。结果显示,该酵母的最大比生长速率μmax随着葡萄糖浓度的增加而有所降低,且呈线性关系:μmax=0.3161-4.1820×104s(100g/L相似文献   

Factors influencing productivity of fermentations employing recombinant microorganisms

Advances in molecular biology and the exploitation of recombinant DNA procedures for the expression of heterologous genes in microbial hosts offer an opportunity to develop fermentation processes more scientifically and less empirically than has been feasible previously. Nevertheless, the highly interdisciplinary nature of the task makes this a complex undertaking. The relationships between microbial physiology and plasmid copy number, plasmid stability, and gene expression are not well documented for host/vector systems and appear to be highly system specific. In an effort to account for these complex biological interactions which can exceed our intuitive capabilities, mathematical models have been designed to aid in process analysis and development activities. Fermentation strategies based on certain physiological assumptions are beginning to be reported for recombinant systems. Representative efforts in these areas indicate the broad scope of considerations involved in developing fermentation processes for recombinant microorganisms and the opportunities for further research in this field.     

Protein misfolding and aggregation research: Some thoughts on improving quality and utility

Once misfolded and aggregated proteins were as interesting as yesterday's trash, just a bothersome byproduct of productive activities. Today, they attract sustained interest from both basic researchers and practicing engineers. In the burgeoning biopharmaceutical industry, protein misfolding and aggregation pose significant challenges to the economic manufacture of safe and effective protein products. In the clinic, protein aggregates are believed to be pathological agents in a number of serious neurodegenerative disorders, such as Alzheimer's and Parkinson's. Over the past few years, the quantity of research into biotechnological aspects of protein misfolding and aggregation has skyrocketed. However, the quality of the published work is quite variable. In this brief opinion piece, we describe what we believe are some key features of high‐quality publications in protein aggregation. We focus on experimental studies that may also have a kinetic modeling component. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:1109–1115, 2013     

酶促水解大豆分离蛋白动力学模型的研究

本文对AS1.398中性蛋白酶在pH6.9和温度49℃条件下水解大豆分离蛋白的动力学机制进行了研究．结果表明：酶水解速率随水解反呈指数递减．为了解释实验结果,我们提出了如下假设：对底物而言水解反应终为零级反应,水解过程中由于游离酶攻击酶-底物中间络合物而造成的不可逆酶变性是一个二级动力学过程．在此基础上,由实验数据推导得到了描述AS1.398中性蛋白酶催化水解大豆分离蛋白的动力学方程,该方程可用于指导和优化酶解反应实验．     

Unusual Fatty Acids with Specific Odor from Mature Male Goat

Unusual five 4-ethyl-fatty acids were estimated as main constituents of sebaceous gland secretion of male goat which showed the releaser pheromone activity against the estrous female. These acids exist in both free state and ester form. The structures were confirmed by synthesis. Among the five acids, 4-ethyloctanoic acid showed the strong goaty odor at low concentration.     

Design of Methylprednisolone Biodegradable Microspheres Intended for Intra-articular Administration

This study aimed to design methyprednisolone (MP)-loaded poly(d,l lactide-co-glycolide) (PLGA) microspheres (MS) intended for intra-articular administration. MP was encapsulated in four different types of PLGA by using an S/O/W technique. The effects of β-irradiation at the dose of 25 kGy were evaluated on the chemical and physicochemical properties of MS and the drug release profiles. The S/O/W technique with hydroxypropylmethylcellulose (HPMC) as surfactant allowed obtaining MS in the tolerability size (7–50 μm) for intra-articular administration. The MP encapsulation efficiency ranged 56–60%. HPMC traces were evidenced in the loaded and placebo MS by attenuated total reflectance Fourier transform infrared spectroscopy. MS made of the capped PLGA DL5050 2M (MS 2M) and uncapped PLGA DL5050 3A (MS 3A) prolonged the release of MP over a 2- to 3-month period with a triphasic (burst release–dormant period–second release pulse) and biphasic release pattern, respectively. The β-irradiation did not significantly alter the morphology, chemical, and physicochemical properties of MS. The only variation was evidenced in the drug release for MS 2M in term of shorting of the dormant period. The minimal variations in the properties of irradiated PLGA MS, which are in disagreement with literature data, may be attributed to a radioprotecting effect exerted by HPMC.     

Attachment and growth kinetics of anchorage-dependent BHK cells on microcarriers

Anchorage-dependent Baby Hamster Kidney (BHK) cells were cultivated on polyhydroxyethylmethacrylate (PHEMA), polystyrene (PS), and Cytodex microcarriers. Analysis of the experimental data indicated that there were a finite number of sites on the microcarrier surfaces, available for anchorage. The number of these sites was determined by the chemical and physical structure of the surface. A small fraction of these sites were suitable for attachment of the cells before proliferation. A larger fraction of these sites did not support attachment but the cells could proliferate on them by the help of previously attached mother cells. The attachment and proliferation of the BHK cells on these microcarriers were satisfactorily modeled by surface saturation type of mathematical expressions.