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Buu N. Tran Li Zhang Robert Jansing Kenneth Aldous 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2009,877(11-12):1109-1116
Optimization of analytical instrumentation is essential when analyses of persistent organic pollutants in human serum are performed at ultra-trace levels. This research describes the analysis of polychlorinated biphenyls (PCBs) in serum using gas chromatography coupled with a mass selective detector (GC/MSD) in the selected ion monitoring (SIM) mode. We selected PCB-58 and PCB-186 as internal standards (ISs) for the method development, and newborn calf serum (NCS) was chosen as the matrix. The matrix was fortified with PCB congeners and extracted by an automated solid phase extraction system using C18 sorbent. The extracts were analyzed at two ion source temperatures, 230 and 300 °C. The use of high ion source temperature increased the abundances of high-mass ions, and the response factors in SIM mode for PCBs. An excellent linearity from 0.5 to 100 ng/ml at ion source temperature of 300 °C was demonstrated, with a calculated detection limit of 0.1 ng/g serum. Seven replicate fortifications of newborn calf serum, at three spiking levels of 1, 10, and 50 ng/g of serum, gave mean recoveries of 110%, 85%, and 98%, with average relative standard deviation (RSD) values of 5.4%, 7.3%, and 4.7%, respectively. 相似文献
965.
Md Nawajes A. Mandal Jagan M.R. Patlolla Lixin Zheng Martin-Paul Agbaga Julie-Thu A. Tran Lea Wicker Anne Kasus-Jacobi Michael H. Elliott Chinthalapally V. Rao Robert E. Anderson 《Free radical biology & medicine》2009,46(5):672-679
Age-related macular degeneration (AMD) is a complex disease that has potential involvement of inflammatory and oxidative stress-related pathways in its pathogenesis. In search of effective therapeutic agents, we tested curcumin, a naturally occurring compound with known anti-inflammatory and antioxidative properties, in a rat model of light-induced retinal degeneration (LIRD) and in retina-derived cell lines. We hypothesized that any compound effective against LIRD, which involves significant oxidative stress and inflammation, would be a candidate for further characterization for its potential application in AMD. We observed significant retinal neuroprotection in rats fed diets supplemented with curcumin (0.2% in diet) for 2 weeks. The mechanism of retinal protection from LIRD by curcumin involves inhibition of NF-κB activation and down-regulation of cellular inflammatory genes. When tested on retina-derived cell lines (661W and ARPE-19), pretreatment of curcumin protected these cells from H2O2-induced cell death by up-regulating cellular protective enzymes, such as HO-1, thioredoxin. Since, curcumin with its pleiotropic activities can modulate the expression and activation of many cellular regulatory proteins such as NF-κB, AKT, NRF2, and growth factors, which in turn inhibit cellular inflammatory responses and protect cells; we speculate that curcumin would be an effective nutraceutical compound for preventive and augmentative therapy of AMD. 相似文献
966.
We present a biophysically based kinetic model of the cardiac SERCA pump that consolidates a range of experimental data into a consistent and thermodynamically constrained framework. The SERCA model consists of a number of sub-states with partial reactions that are sensitive to Ca2+ and pH, and to the metabolites MgATP, MgADP, and Pi. Optimization of model parameters to fit experimental data favors a fully cooperative Ca2+-binding mechanism and predicts a Ca2+/H+ counter-transport stoichiometry of 2. Moreover, the order of binding of the partial reactions, particularly the binding of MgATP, proves to be a strong determinant of the ability of the model to fit the data. A thermodynamic investigation of the model indicates that the binding of MgATP has a large inhibitory effect on the maximal reverse rate of the pump. The model is suitable for integrating into whole-cell models of cardiac electrophysiology and Ca2+ dynamics to simulate the effects on the cell of compromised metabolism arising in ischemia and hypoxia. 相似文献
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The potential for personalized cancer management has long intrigued experienced researchers as well as the na?ve student intern. Personalized cancer treatments based on a tumor's genetic profile are now feasible and can reveal both the cells' susceptibility and resistance to chemotherapeutic agents. In a weeklong laboratory investigation that mirrors current cancer research, undergraduate and advanced high school students determine the efficacy of common pharmacological agents through in vitro testing. Using mouse mammary tumor cell cultures treated with "unknown" drugs historically recommended for breast cancer treatment, students are introduced to common molecular biology techniques from in vitro cell culture to fluorescence microscopy. Student understanding is assessed through laboratory reports and the successful identification of the unknown drug. The sequence of doing the experiment, applying logic, and constructing a hypothesis gives the students time to discover the rationale behind the cellular drug resistance assay. The breast cancer experiment has been field tested during the past 5 yr with more than 200 precollege/undergraduate interns through the Gains in the Education of Mathematics and Science program hosted by the Walter Reed Army Institute of Research. 相似文献
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Plasma microparticles (MPs) are spherical cell membrane fragments derived from either apoptotic or activated cells. Characterized by a rich phospholipid moiety and many protein constituents, MPs normally circulate in the blood and contribute to numerous physiological processes. In disease states, MPs derived from the injured organ likely contain valuable markers for determining the site, type, and extent of disease pathology. However, the basic protein characteristics of plasma MPs have yet to be described. In this study, MPs from a pooled plasma sample derived from 16 healthy donors, all of group A blood type, were prepared by ultracentrifugation. Flow cytometry confirmed that a majority of these MPs are smaller than 1 microm. Factor Xa generation assay revealed the presence of tissue factor activity in these MPs, confirming MPs' role in initiating blood coagulation. The MP proteome was analyzed by two-dimensional (2-D) gel electrophoresis performed in triplicate, and compared with a 2-D gel of pooled whole plasma and blood platelets. Overall, plasma MPs displayed distinct protein features and a greater number of protein spots (1021-1055) than that detected in whole plasma (331-370). Protein spots expressed in high abundance in the MP proteome were then excised and submitted for protein identity determination. This process provided protein identification for 169 protein spots and reported their relative protein quantities within the MP proteome. These 169 protein spots represented 83 different proteins and their respective isoforms. Thirty of these proteins have never before been reported in previous proteome analyses of human plasma. These results provide unprecedented information on the MP proteome and create a basis for future studies to understand MP biology and pathophysiology. 相似文献
970.
Tchilibon S Kim SK Gao ZG Harris BA Blaustein JB Gross AS Duong HT Melman N Jacobson KA 《Bioorganic & medicinal chemistry》2004,12(9):2021-2034
We synthesized phenyl ring-substituted analogues of N(6)-(1S,2R)-(2-phenyl-1-cyclopropyl)adenosine, which is highly potent in binding to the human A(3)AR with a Ki value of 0.63 nM. The effects of these structural changes on affinity at human and rat adenosine receptors and on intrinsic efficacy at the hA(3)AR were measured. A 3-nitrophenyl analogue was resolved chromatographically into pure diastereomers, which displayed 10-fold stereoselectivity in A(3)AR binding in favor of the 1S,2R isomer. A molecular model defined a hydrophobic region (Phe168) in the putative A(3)AR binding site around the phenyl moiety. A heteroaromatic group (3-thienyl) could substitute for the phenyl moiety with retention of high affinity of A(3)AR binding. Other related N(6)-substituted adenosine derivatives were included for comparison. Although the N(6)-(2-phenyl-1-cyclopropyl) derivatives were full A(3)AR agonists, several other derivatives had greatly reduced efficacy. N(6)-Cyclopropyladenosine was an A(3)AR antagonist, and adding either one or two phenyl rings at the 2-position of the cyclopropyl moiety restored efficacy. N(6)-(2,2-Diphenylethyl)adenosine was an A(3)AR antagonist, and either adding a bond between the two phenyl rings (N(6)-9-fluorenylmethyl) or shortening the ethyl moiety (N(6)-diphenylmethyl) restored efficacy. A QSAR study of the N(6) region provided a model that was complementary to the putative A(3)AR binding site in a rhodopsin-based homology model. Thus, a new series of high-affinity A(3)AR agonists and related nucleoside antagonists was explored through both empirical and theoretical approaches. 相似文献