University of Southern Nevada
University of Southern Nevada
Dey S.,University of Southern Nevada
Expert Opinion on Drug Metabolism and Toxicology | Year: 2011
In recent times, there has been an ever increasing demand for ocular drugs to treat sight threatening diseases such as glaucoma, age-related macular degeneration and diabetic retinopathy. As more drugs are developed, there is a great need to test in vitro permeability of these drugs to predict their efficacy and bioavailability in vivo. Corneal cell culture models are the only tool that can predict drug absorption across ocular layers accurately and rapidly. Cell culture studies are also valuable in reducing the number of animals needed for in vivo studies which can increase the cost of the drug developmental process. Currently, rabbit corneal cell culture models are used to predict human corneal absorption due to the difficulty in human corneal studies. More recently, a three dimensional human corneal equivalent has been developed using three different cell types to mimic the human cornea. In the future, human corneal cell culture systems need to be developed to be used as a standardized model for drug permeation. © 2011 Informa UK, Ltd.
Frick L.J.,University of Southern Nevada
American journal of pharmaceutical education | Year: 2011
To identify stress and stress-relieving mechanisms among second-year pharmacy students in a 3-year doctor of pharmacy (PharmD) program using a Mastery Learning Educational Model and to compare findings with those from a 4-year program. Second-year PharmD students in a 3-year program were asked to complete a series of questionnaires including the Perceived Stress Scale (PSS) regarding stress and stress-relieving activities. The average PSS score for the 3-year PharmD cohort was significantly higher than the score of demographically similar students enrolled in a 4-year PharmD program (P = 0.04). There were significant differences between the 2 groups' scores on 5 items on the PSS including how often they: were upset because something happened unexpectedly, felt unable to control important things, felt nervous and stressed, thought about things that had to be accomplished, and were able to control the way they spent their time. The rate of prescription drug misuse among those in the 3-year PharmD program was 11.6%. Students in a 3-year PharmD program with a unique educational model experienced more stress than students in a traditional 4-year PharmD program.
Frick L.J.,University of Southern Nevada |
Frick J.L.,University of Southern Nevada |
Coffman R.E.,University of Southern Nevada |
Dey S.,University of Southern Nevada
American Journal of Pharmaceutical Education | Year: 2011
Objective. To identify stress and stress-relieving mechanisms among second-year pharmacy students in a 3-year doctor of pharmacy (PharmD) program using a Mastery Learning Educational Model and to compare findings with those from a 4-year program. Methods. Second-year PharmD students in a 3-year program were asked to complete a series of questionnaires including the Perceived Stress Scale (PSS) regarding stress and stress-relieving activities. Results. The average PSS score for the 3-year PharmD cohort was significantly higher than the score of demographically similar students enrolled in a 4-year PharmD program (P = 0.04). There were significant differences between the 2 groups' scores on 5 items on the PSS including how often they: were upset because something happened unexpectedly, felt unable to control important things, felt nervous and stressed, thought about things that had to be accomplished, and were able to control the way they spent their time. The rate of prescription drug misuse among those in the 3-year PharmD program was 11.6%. Conclusions. Students in a 3-year PharmD program with a unique educational model experienced more stress than students in a traditional 4-year PharmD program.
Adams-Haduch J.M.,University of Pittsburgh |
Onuoha E.O.,University of Pittsburgh |
Bogdanovich T.,University of Pittsburgh |
Tian G.-B.,University of Pittsburgh |
And 8 more authors.
Journal of Clinical Microbiology | Year: 2011
Acinetobacter baumannii is emerging as an important nosocomial pathogen worldwide. We report molecular epidemiology of 65 carbapenem-nonsusceptible A. baumannii isolates identified from hospitals in New York, Pennsylvania, Florida, Missouri, Nevada, and California between 2008 and 2009. All isolates were subjected to pulsed-field gel electrophoresis (PFGE). Select isolates then underwent multilocus sequence typing (MLST). While the PFGE patterns tended to cluster within each hospital, sequence types (STs) belonging to the clonal complex 92 (CC92) and the pan-European clonal lineage II (EUII; worldwide clonal lineage 2) were predominant in all hospitals. Of them, ST122 and ST208 were the most common and were found in four of the six hospitals. Isolates belonging to the pan-European clonal lineages I and III were identified in one hospital each. Carbapenemase-encoding genes bla OXA-23 and/or ISAba1-bla OXA-51-like were present among the majority of isolates. These findings suggest that carbapenem-nonsusceptible A. baumannii isolates found in U.S. hospitals constitute part of the global epidemic driven by CC92, but have unique STs other than ST92, which may be spreading by means of patient transfer between health care facilities within the United States. Copyright © 2011, American Society for Microbiology. All Rights Reserved.
Scott M.A.,University of Southern Nevada |
Nguyen V.T.,University of California at Los Angeles |
Levi B.,Stanford University |
James A.W.,University of California at Los Angeles
Stem Cells and Development | Year: 2011
There has been a recent increase in our understanding in the isolation, culture, and differentiation of mesenchymal stem cells (MSCs). Concomitantly, the availability of MSCs has increased, with cells now commercially available, including human MSCs from adipose tissue and bone marrow. Despite an increased understanding of MSC biology and an increase in their availability, standardization of techniques for adipogenic differentiation of MSCs is lacking. The following review will explore the variability in adipogenic differentiation in vitro, specifically in 3T3-L1 and primary MSCs derived from both adipose tissue and bone marrow. A review of alternative methods of adipogenic induction is also presented, including the use of specific peroxisome proliferator- activated receptor-gamma agonists as well as bone morphogenetic proteins. Finally, we define a standard, commonly used adipogenic differentiation medium in the hopes that this will be adopted for the future standardization of laboratory techniques-however, we also highlight the essentially arbitrary nature of this decision. With the current, rapid pace of electronic publications, it becomes imperative for standardization of such basic techniques so that interlaboratory results may be easily compared and interpreted. © Copyright 2011, Mary Ann Liebert, Inc.
Leung E.L.-H.,University of Hong Kong |
Fiscus R.R.,Nevada Cancer Institute |
Fiscus R.R.,University of Southern Nevada |
Tung J.W.,Nevada Cancer Institute |
And 7 more authors.
PLoS ONE | Year: 2010
Background: The cancer stem cell theory hypothesizes that cancers are perpetuated by cancer stem cells (CSC) or tumor initiating cells (TIC) possessing self-renewal and other stem cell-like properties while differentiated non-stem/initiating cells have a finite life span. To investigate whether the hypothesis is applicable to lung cancer, identification of lung CSC and demonstration of these capacities is essential. Methodology/Principal Finding: The expression profiles of five stem cell markers (CD34, CD44, CD133, BMI1 and OCT4) were screened by flow cytometry in 10 lung cancer cell lines. CD44 was further investigated by testing for in vitro and in vivo tumorigenecity. Formation of spheroid bodies and in vivo tumor initiation ability were demonstrated in CD44+ cells of 4 cell lines. Serial in vivo tumor transplantability in nude mice was demonstrated using H1299 cell line. The primary xenografts initiated from CD44+ cells consisted of mixed CD44+ and CD44- cells in similar ratio as the parental H1299 cell line, supporting in vivo differentiation. Semi-quantitative Real-Time PCR (RT-PCR) showed that both freshly sorted CD44+ and CD44+ cells derived from CD44+-initiated tumors expressed the pluripotency genes OCT4/POU5F1, NANOG, SOX2. These stemness markers were not expressed by CD44- cells. Furthermore, freshly sorted CD44+ cells were more resistant to cisplatin treatment with lower apoptosis levels than CD44- cells. Immunohistochemical analysis of 141 resected non-small cell lung cancers showed tumor cell expression of CD44 in 50.4% of tumors while no CD34, and CD133 expression was observed in tumor cells. CD44 expression was associated with squamous cell carcinoma but unexpectedly, a longer survival was observed in CD44-expressing adenocarcinomas. Conclusion/Significance: Overall, our results demonstrated that stem cell-like properties are enriched in CD44-expressing subpopulations of some lung cancer cell lines. Further investigation is required to clarify the role of CD44 in tumor cell renewal and cancer propagation in the in vivo environment.© 2010 Leung et al.
Leung E.L.,University of Nevada, Las Vegas |
Leung E.L.,Chinese University of Hong Kong |
Wong J.C.,University of Nevada, Las Vegas |
Johlfs M.G.,University of Nevada, Las Vegas |
And 6 more authors.
Molecular Cancer Research | Year: 2010
Previously, we showed that basal activity of nitric oxide (NO)/cyclic GMP (cGMP)/protein kinase G (PKG) signaling pathway protects against spontaneous apoptosis and confers resistance to cisplatin-induced apoptosis in human ovarian cancer cells. The present study determines whether basal PKG kinase activity regulates Src family kinase (SFK) activity and proliferation in these cells. PKG-Iα was identified as predominant isoform in both OV2008 (cisplatin-sensitive, wild-type p53) and A2780cp (cisplatin-resistant, mutated p53) ovarian cancer cells. In both cell lines, ODQ (inhibitor of endogenous NO-induced cGMP biosynthesis), DT-2 (highly specific inhibitor of PKG-Iα kinase activity), and PKG-Iα knockdown (using small interfering RNA) caused concentration-dependent inhibition of DNA synthesis (assessed by bromodeoxyuridine incorporation), indicating an important role of basal cGMP/PKG-Iα kinase activity in promoting cell proliferation. DNA synthesis in OV2008 cells was dependent on SFK activity, determined using highly selective SFK inhibitor, 4-(4′-phenoxyanilino)-6,7-dimethoxyquinazoline (SKI-1). Studies using DT-2 and PKG-Iα small interfering RNA revealed that SFK activity was dependent on PKG-Iα kinase activity. Furthermore, SFK activity contributed to endogenous tyrosine phosphorylation of PKG-Iα in OV2008 and A2780cp cells. In vitro coincubation of recombinant human c-Src and PKG-Iα resulted in c-Src-mediated tyrosine phosphorylation of PKG-Iα and enhanced c-Src autophosphorylation/activation, suggesting that human c-Src directly tyrosine phosphorylates PKG-Iα and the c-Src/PKG-Iα interaction enhances Src kinase activity. Epidermal growth factor-induced stimulation of SFK activity in OV2008 cells increased PKG-Iα kinase activity (indicated by Ser239 phosphorylation of the PKG substrate vasodilator-stimulated phosphoprotein), which was blocked by both SKI-1 and SU6656. The data suggest an important role of Src/PKG-Iα interaction in promoting DNA synthesis/cell proliferation in human ovarian cancer cells. The NO/cGMP/PKG-Iα signaling pathway may provide a novel therapeutic target for disrupting ovarian cancer cell proliferation. ©2010 AACR.
Wong J.C.,Nevada Cancer Institute |
Wong J.C.,University of Nevada, Las Vegas |
Fiscus R.R.,Nevada Cancer Institute |
Fiscus R.R.,University of Nevada, Las Vegas |
Fiscus R.R.,University of Southern Nevada
Journal of Cellular Biochemistry | Year: 2011
Inappropriate signaling conditions within bone marrow stromal cells (BMSCs) can lead to loss of BMSC survival, contributing to the loss of a proper micro-environmental niche for hematopoietic stem cells (HSCs), ultimately causing bone marrow failure. In the present study, we investigated the novel role of endogenous atrial natriuretic peptide (ANP) and the nitric oxide (NO)/cGMP/protein kinase G type-Iα (PKG-Iα) signaling pathway in regulating BMSC survival and proliferation, using the OP9 BMSC cell line commonly used for facilitating the differentiation of HSCs. Using an ANP-receptor blocker, endogenously produced ANP was found to promote cell proliferation and prevent apoptosis. NO donor SNAP (S-nitroso-N- acetylpenicillamine) at low concentrations (10 and 50 μM), which would moderately stimulate PKG activity, protected these BMSCs against spontaneous apoptosis. YC-1, a soluble guanylyl cyclase (sGC) activator, decreased the levels of apoptosis, similar to the cytoprotective effects of low-level NO. ODQ (1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one), which blocks endogenous NO-induced activation of sGC and thus lowers endogenous cGMP/PKG activity, significantly elevated apoptotic levels by 2.5- and three-fold. Pre-incubation with 8-Bromo-cGMP or ANP, which bypass the ODQ block, almost completely prevented the ODQ-induced apoptosis. A highly-specific PKG inhibitor, DT-3, at 20, and 30 mM, caused 1.5- and two-fold increases in apoptosis, respectively. ODQ and DT-3 also decreased BMSCs proliferation and colony formation. Small Interfering RNA gene knockdown of PKG-Iα increased apoptosis and decreased proliferation in BMSCs. The data suggest that basal NO/cGMP/PKG-Iα activity and autocrine ANP/cGMP/PKG-Iα are necessary for preserving OP9 cell survival and promoting cell proliferation and migration. © 2010 Wiley-Liss, Inc.
Bachmeier C.J.,Roskamp Institute |
Beaulieu-Abdelahad D.,Roskamp Institute |
Ganey N.J.,Roskamp Institute |
Mullan M.J.,Roskamp Institute |
And 2 more authors.
Biopharmaceutics and Drug Disposition | Year: 2011
Venlafaxine and its metabolite desvenlafaxine are serotonin-norepinephrine reuptake inhibitors currently prescribed for the treatment of depression. Previously, it was reported that venlafaxine is an inducer of MDR1, the gene responsible for P-glycoprotein (P-gp). The present study expanded upon these findings by examining the effect of venlafaxine and desvenlafaxine on the expression of both P-gp and the breast cancer resistance protein (BCRP) in human brain endothelial cells (HBMEC), an in vitro model of the blood-brain barrier (BBB). The HBMEC were treated for 1 h with various concentrations (500 nM to 50 μM) of venlafaxine and desvenlafaxine. Western blot analysis revealed treatment with venlafaxine significantly induced the expression of P-gp (2-fold) and BCRP (1.75-fold) in a dose-dependent manner, while treatment with desvenlafaxine had no effect on drug efflux transporter expression. To determine the functional significance of this effect, the permeability of a known drug efflux probe, rhodamine 123, across the BBB model and Caco-2 cells, a model of intestinal absorption, were examined. Treatment with venlafaxine (1-50 μM) for 1 h significantly reduced the apical-to-basolateral permeability of R123 across the BBB model (30%) and Caco-2 cell monolayers (25%), indicative of increased drug efflux transporter expression at the apical membrane. Conversely, desvenlafaxine had no effect on R123 permeability in either cellular model. These studies indicate that venlafaxine, but not desvenlafaxine is an inducer of drug efflux transporter expression, which consequently increases the potential for clinical drug-drug interactions. Therefore, based on these preliminary results, caution should be taken when prescribing venlafaxine with other P-gp substrates. Copyright © 2011 John Wiley & Sons, Ltd.
Hatcher D.C.,University of Southern Nevada
Sleep Medicine Clinics | Year: 2010
Imaging plays a role in the anatomic assessment of the airway and adjacent structures. This article discusses the use of 3-dimensional (3D) imaging (cone beam computed tomography [CBCT]) to evaluate the airway and selected regional anatomic variables that may contribute to obstructive sleep-disordered breathing (OSDB) in patients. CBCT technology uses a cone-shaped x-ray beam with a special image intensifier and a solid-state sensor or an amorphous silicon plate for capturing the image. Incorporation of 3D imaging into daily practice will allow practitioners to readily evaluate and screen patients for phenotypes associated with OSDB. © 2010 Elsevier Inc. All rights reserved.