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HPLC-UV Analysis of Bupropion and Hydroxybupropion : Application to In Vivo Pharmacokinetic Drug-Drug Interaction Studies Between Bupropion and Potent CYP2B6 Inhibitors
No full textAdvisor: Alan L. MyersBupropion is a popular antidepressant that is also prescribed in the management of smoking cessation. In humans, bupropion is predominantly metabolized to its active metabolite hydroxybupropion by CYP2B6. Inhibitors of CYP2B6 have the potential to decrease the clearance of bupropion, leading to
adverse drug toxicity. We sought to develop a sensitive HPLC-UV assay to quantify plasma and
brain concentrations of bupropion and hydroxybupropion; and apply the assay to assess in vivo pharmacokinetic (PK) drug-drug interaction (DDI) studies between bupropion and potent CYP2B6 inhibitors. Tissue extraction followed by HPLC-UV detected timolol (IS), hydroxybupropion and bupropion at 6, 11 and 36 minutes, respectively. The LOD for both compounds was 6.0 ng/ml, and the intra-day
and inter-day coefficients of variation was ±12% in plasma and ±15% in whole brain tissue. We then utilized this novel technique to evaluate the PK of bupropion and hydroxybupropion following repeated
administration of the known CYP2B6 inhibitor ticlopidine (5 mg/kg daily x 5 days) in CF-1
mice. Ticlopidine increased the plasma area under the concentration curve (AUC) of bupropion (2.0-fold,p 0.05)and decreased the AUC of hydroxybupropion
(2.0-fold;p< 0.001). In summary, we have developed a sensitive HPLC assay and suitable rodent model to evaluate in vivo PK DDI between bupropion and CYP2B6 inhibitors.Drake University, Department of Pharmaceutical, Biomedical and Administrative Science
Influence of Exogenous PlGF on Apoptosis in the H9c2 Cardiomyoblast Cell Line
No full textAdvisor: Ronald TorryPlacenta growth factor (PlGF) is known to inhibit apoptosis in cells such as trophoblast or endothelial cells. Although PlGF is expressed in heart tissue in vivo and in vitro, little is known about its antiapoptotic
effects in cardiomyocytes. H9c2 cells (a rat cardiomyoblast cell line) were used to determine
if PlGF can protect these cells from oxidative-induced apoptosis. Cells were cultured and then
treated with hydrogen peroxide (H2O2) to induce apoptosis. An H2O2 dose response curve was performed and showed increased concentrations of H2O2 were associated with increased percent apoptosis: 25uM H2O2 = 36.77±8.9%; 50uM H2O2 = 47.53±4.6%; and 100uM H2O2 = 61.36±5.1%
apoptosis. Some cultures were then pre-treated with either 10ng/mL or 50ng/mL of exogenous recombinant mouse P1GF for 24 hours and then incubated with 50uM H2O2 for 2 hours. Cells were stained with 4',6-diamidino-2-phenylindole (DAPI), a fluorescent stain that binds strongly to DNA and then fixed with ice cold acetone. Apoptotic cells were recognized by the condensed, fragmented, and degraded nuclei with fluorescence microscopy. Random fields of cells from each treatment group were chosen to count the apoptotic cells and percent of apoptosis was calculated for each field. Control cultures
showed 12.41±0.5% apoptosis, H2O2+0ng/mL PlGF = 46.49±1.5% apoptosis, H2O2+10ng/mL PlGF = 30.48±5.9% apoptosis, and H2O2+50ng/mL PlGF = 33.70±5.8% apoptosis. In conclusion, we
have developed a consistent method to induce apoptosis in H9c2 cells and used this to show that although exogenous PlGF tended to protect H9c2 cells from oxidative-induced apoptosis, this difference did not attain statistical significance.Drake University, Pharmaceutical, Biomedical, and Admininstrative Science Departmen
Drake Neighborhood Oral History with Don Wine
No full textTranscript of an oral history interview about the life of Donald Wine, his experiences as a Drake University student in the early 1940s and what it was like living in what is now the Drake Neighborhood. Interview conducted by a Drake University student in 2010
Development of the System Selectivity Cube
No full textAdvisors: Mark F. Vitha, Timothy UrnessThe goal of chromatography is to separate components of a mixture. There are a number of different systems that can be used to achieve this, and each will separate the components to varying extents according to their chemical properties. The difficulty lies in that there are thousands of different systems available. We developed a three dimensional visualization tool that allows simultaneous comparison of systems in order to efficiently select a different combination to improve selectivity and
successfully separate solutes. The model relies on linear solvation energy relationships (LSERs), which quantify the interaction abilities of systems. We compare two systems to one another by performing a linear regression on the coefficients of the LSER equation. According to this regression, we classify the relationship of two systems as identical, similar, or different based on the energetics of
the systems that govern retention. The comparisons are then plotted in a three dimensional cube according to the slope, intercept, and correlation coefficient (r2) value of the regression. The position of
the point corresponds to the energy relationship of the two systems. When using a system that does not adequately separate the components of a mixture, the cube makes it simple to visually select another system with a different energetic relationship, and thus one which might produce a better separation.
This technique is applicable to all forms of chromatography, and has been implemented with
74 MEKC systems and 370 RPLC systems successfully.Drake University, Department of Chemistry, Department of Mathematics and Computer Scienc
Assessing Resveratrol Phuronic F 127 Micelle Stability in the Presence of Plasma Proteins Using Fluorescence Resonance Energy Transfer (FRET)
No full textAdvisor: Deepa A. RaoResveratrol (RES) is a polyphenolic compound with potential for chemopreventative and chemotherapeutic uses. However, exploration has been hindered by its short biologic half-life of ~6 minutes. Using polymeric micelles composed of Pluronic® F 127 may be a way to enhance the in vivo half-life of RES. Our objective is to investigate the in vitro stability of RES-5 mg/ml F127 formulation using
FRET. DiI and DiO were used as the FRET fluorophore pair & incorporated into the micelle. In an intact micelle, no loss of signal is seen. However, when the system destabilizes, loss of signal is noted. The FRET pair was excited at 484 nm & emission was detected at 505 nm (DiO) & 570 nm (DiI). In vitro stability of micelles with and without RES was evaluated in the absence and presence
of plasma proteins: albumin, α-β- and γ-globulins. F 127 micelles without RES were destabilized in the presence of plasma proteins in a statistically significant manner over a two hour time period. F127 micelles with RES are destabilized primarily by dilution. These micelles are re-stabilized in the presence
of plasma proteins in a statistically significant manner, however the stabilization does not lead to complete recovery of micelle stability as compared to F127 micelles without RES. Based on these findings, F 127- RES formulation is more susceptible to dilution than plasma protein based destabilization.
Further study in an in vivo model must be explored to validate the in vitro findings.Drake University, Department of Pharmaceutical, Biomedical, and Administrative Science
Comparison of Soccer Knowledge and Performance : Examination of Slalom Dribble Time and Various Knowledge Parameters
No full textAdvisor: David S. SenchinaPerformance in athletic events is based on a blend of declarative and procedural knowledge. The purpose of this experiment was to determine the relationship between declarative and procedural knowledge of soccer. In particular, the relationship between score on a test of soccer regulations, roles, rules, techniques, and terms and completion time of a slalom dribbling drill were examined. It was
hypothesized that individuals who scored higher on the theoretical knowledge test would have lower slalom times. The slalom dribbling drill was performed between five cones placed 2.5 m apart and was timed. An untimed paper-based test evaluating various soccer knowledge parameters was also taken. An inverse relationship was found between all written test subsets as well as overall results and slalom completion time. Scores in overall test, rules subset, and terms subset were significantly
higher in those individuals who completed the slalom in less than the median slalom completion time. Total foot contacts, and specifically total left foot contacts, were significantly greater in individuals
who completed the slalom in more than the median slalom completion time. Faster individuals reported a greater total number of soccer experiences in their personal history, possibly accounting for these differences.Drake University, Biochemistry, Cell, and Molecular Biology Program, Department of Chemistry, Department of Biolog
Do Small, Urban Restorations Create Habitat for Regionally Declining Plant and Animal Species?
No full textAdvisor: Keith SummervilleCollaborative efforts are often important in achieving ecological goals. We partnered with SE Polk High School to create a peer-mentoring research team with two goals: (1) to build environmental education into the high school biology classroom and (2) to ascertain if ecological restoration protects species diversity. In the summer of 2009, we sampled a 77 acre restored prairie easement at Metro
Park East. This inventory allowed us to generate a set of baseline data to test the hypothesis that ecosystem restoration succeeds at protecting native species, even in an urban landscape. To produce our inventory, we created a multi-arrayed sampling methodology, based on non-lethal techniques. We used track identification, Sherman live trapping and drift fencing to collect vertebrates. For invertebrates, we used aerial netting to collect samples. Plants were identified when in bloom. We sampled a total of 68 animal species and 46 plant species. Nine species that are in regional decline were discovered: bobolink, dickcissle, sedge wren, grasshopper sparrow, yellow-billed cuckoo, red-headed woodpecker, bull snake, ring-necked snake and wild indigo duskywing. These represent 6 birds, 2 snakes, and one butterfly. Our results also allowed us to create a set of future erosion and invasive
species management strategies for Metro Park East. Future work will attempt to experimentally increase habitat for the nine species of regional conservative concern.Drake University, Environmental Science and Policy Progra
Comparison of the Symptoms Caused by Three Geminiviruses in a Common Host
No full textAdvisor: Linda Hanley-Bowdoin; North Carolina State UniversityThe Geminiviridae are a family of single-stranded DNA plant viruses that cause severe crop destruction especially in the tropics. Much of the research into geminivirus replication and resistance is conducted
in model organisms such as Nicotiana benthamiana, which is not the natural host of the viruses. Model plants are used because of their ease of cultivation and shorter generation times. Typically, begomoviruses have narrow host ranges and cannot be compared directly. However, unlike many plant species, N. benthamiana is susceptible to a variety of begomoviruses and can be used to compare them in a common host. In this study, we compare the disease properties of three begomoviruses
whose natural hosts include cabbage and cassava, which represent two families – the Brassicaceae and Euphorbiaceae. These studies examine Cabbage leaf curl virus (CaLCuV), African cassava mosaic virus-Cameroon
(ACMV-Cam) and East African cassava mosaic virus-Uganda (EACMV-UG3). CaLCuV infects cabbage, cauliflower and broccoli fields in the U.S. The two cassava-infecting viruses are part of a disease complex that causes Cassava Mosaic Disease (CMD) in Africa. CMD is pandemic across Africa, resulting insufficient food supplies. We infected N. benthamiana with ACMV-Cam and EACMVUG3 by bombardment of cloned viral sequences. CaLCuV was inoculated using Agrobacteria carrying viral genomic DNA in T-DNA plasmids. The infected plants were monitored for symptoms and viral DNA accumulation. These studies showed that CaLCuV and ACMV-Cam caused the most severe symptoms on N. benthamiana and were similar in severity. EACMV-UG3 symptoms were significantly
milder.Drake University, Department of Molecular and Structural Biochemistr
Selection Of Switching Sites In All-Optical Network Topology Design
Get PDFIn this paper, we consider the problem of topology design for both unprotected and one-link protected all-optical networks. We investigate the problem of selecting switching sites to minimize total cost of the network. The cost of an optical network is expressed as a sum of three main factors: the site cost, the link cost, and the switch cost.
For unprotected networks with linear cost model, we present a mixed integer linear programming (MILP) formulation of the problem. We also present an efficient heuristic to approximate the solution. The experimental results show good performance of the linear cost model heuristic. In 16% of the experiments with 10 nodes network topologies, the linear cost model heuristic had no error. Moreover, for 54% and 86% of the experiments with 10 nodes network topologies, the linear cost model heuristic’s solution is within 2% and 5% of its optimal value respectively.
Finally, we extend our approach to one-link protected networks, and present an efficient survivable heuristic, and
representative experimental results