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Crystal Structure Of O-Methyltransferase Calo6 From The Calicheamicin Biosynthetic Pathway: A Case Of Challenging Structure Determination At Low Resolution, Oleg V. Tsodikov, Caixia Hou, Christopher T. Walsh, Sylvie Garneau-Tsodikova 2015 University of Kentucky

Crystal Structure Of O-Methyltransferase Calo6 From The Calicheamicin Biosynthetic Pathway: A Case Of Challenging Structure Determination At Low Resolution, Oleg V. Tsodikov, Caixia Hou, Christopher T. Walsh, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

BACKGROUND: Calicheamicins (CAL) are enedyine natural products with potent antibiotic and cytotoxic activity, used in anticancer therapy. The O-methyltransferase CalO6 is proposed to catalyze methylation of the hydroxyl moiety at the C2 position of the orsellinic acid group of CAL.

RESULTS: Crystals of CalO6 diffracted non-isotropically, with the usable data extending to 3.4 Å. While no single method of crystal structure determination yielded a structure of CalO6, we were able to determine its structure by using molecular replacement-guided single wavelength anomalous dispersion by using diffraction data from native crystals of CalO6 and a highly non-isomorphous mercury derivative. The structure …


Initial Evidence Of Endothelial Cell Apoptosis As A Mechanism Of Systemic Capillary Leak Syndrome, Ragheb Assaly, Dan Olson, Jeffrey Hammersley, Pan-Sheng Fan, Jiang Liu, Joseph Shapiro, M. Kahaleh 2015 Marshall University

Initial Evidence Of Endothelial Cell Apoptosis As A Mechanism Of Systemic Capillary Leak Syndrome, Ragheb Assaly, Dan Olson, Jeffrey Hammersley, Pan-Sheng Fan, Jiang Liu, Joseph Shapiro, M. Kahaleh

Jiang Liu

Background: Systemic capillary leak syndrome (SCLS) is a rare disorder of unknown etiology that is characterized by acute recurrent attacks of hypovolemic shock commonly following an inflammatory stimulus such as a viral illness. Prophylactic therapy is generally ineffective, and the outcome is frequently fatal. Methods: In order to investigate the cellular mechanisms leading to SCLS, we examined the effects of sera from two patients with active SCLS on microvascular endothelial cell apoptosis in vitro. Apoptosis was determined by morphologic criteria, DNA fragmentation, annexin V stain, and by a quantitative photometric assay. The apoptotic pathway was investigated by Western blot of …


Grp78/Bip Is Involved In Ouabain-Induced Endocytosis Of The Na/K-Atpase In Llc-Pk1 Cells, Riad Kesiry, Jiang Liu 2015 Marshall University

Grp78/Bip Is Involved In Ouabain-Induced Endocytosis Of The Na/K-Atpase In Llc-Pk1 Cells, Riad Kesiry, Jiang Liu

Jiang Liu

We have demonstrated that ouabain causes dose- and time-dependent decreases both in 86Rb+ uptake and plasmalemmal Na/K-ATPase content of LLC-PK1 cells, which is related to ouabain-induced endocytosis of plasmalemmal Na/K-ATPase in LLC-PK1 cells through a clathrin-dependent mechanism. GRP78/BiP is a resident protein of the endoplasmic reticulum (ER) and acts as a molecular chaperone. Recently, several studies have shown that GRP78/BiP is also expressed on the cell surface and forms heterogeneous, high molecular weight complexes with other proteins. To identify the proteins that are possibly involved in ouabain-induced endocytosis of the Na/K-ATPase in LLC-PK1 cells, we separated and identified endosomal proteins …


Effect Of Green Tea Extract On Cardiac Hypertrophy Following 5/6 Nephrectomy In The Rat, Snigdha Priyadarshi, Brandon Valentine, Chi Han, Olga Fedorova, Alexei Bagrov, Jiang Liu, Sankaridrug Periyasamy, David Kennedy, Deepak Malhorta, Zijian Xie, Joseph Shapiro 2015 Marshall University

Effect Of Green Tea Extract On Cardiac Hypertrophy Following 5/6 Nephrectomy In The Rat, Snigdha Priyadarshi, Brandon Valentine, Chi Han, Olga Fedorova, Alexei Bagrov, Jiang Liu, Sankaridrug Periyasamy, David Kennedy, Deepak Malhorta, Zijian Xie, Joseph Shapiro

Jiang Liu

Background

Left ventricular hypertrophy commonly complicates chronic renal failure. We have observed that at least one pathway of left ventricular hypertrophy appears to involve signaling through reactive oxygen species (ROS). Green tea is a substance that appears to have substantial antioxidant activity, yet is safe and is currently widely used. We, therefore, studied whether green tea supplementation could attenuate the development of left ventricular hypertrophy in an animal model of chronic renal failure.

Methods

Male Sprague-Dawley rats were subjected to sham or remnant kidney surgery and given green tea extract (0.1% and 0.25%) or plain drinking water for the next …


Ouabain And Insulin Induce Sodium Pump Endocytosis In Renal Epithelium, Shalini Gupta, Yanling Yan, Deepak Malhotra, Jiang Liu, Zijian Xie, Sonia Najjar, Joseph Shapiro 2015 Marshall University

Ouabain And Insulin Induce Sodium Pump Endocytosis In Renal Epithelium, Shalini Gupta, Yanling Yan, Deepak Malhotra, Jiang Liu, Zijian Xie, Sonia Najjar, Joseph Shapiro

Jiang Liu

Cardiotonic steroids signaling through the basolateral sodium pump (Na/K-ATPase) have been shown to alter renal salt handling in intact animals. Because the relationship between renal salt handling and blood pressure is a key determinant of hypertension, and patients with insulin resistance are frequently hypertensive, we chose to examine whether there might be competition for resources necessary for receptor-mediated endocytosis. In LLC-PK1 cells, the Na/K-ATPase-α1 and carcinoembryonic antigen cell adhesion molecule 1, a plasma membrane protein that promotes receptor-mediated endocytosis, colocalized in the plasma membranes and translocated to the intracellular region in response to ouabain. Either ouabain or insulin alone caused …


Modeling Of Mpges-1 Three-Dimensional Structures: Applications In Drug Design And Discovery, Chang-Guo Zhan, Xiaoqin Huang, Adel Hamza 2015 University of Kentucky

Modeling Of Mpges-1 Three-Dimensional Structures: Applications In Drug Design And Discovery, Chang-Guo Zhan, Xiaoqin Huang, Adel Hamza

Pharmaceutical Sciences Faculty Patents

This invention relates to representations of prostaglandin synthase three-dimensional structures. Such representations are suitable for designing agents that modulate the activity of the enzyme by binding to the substrate binding domain.


A Modified Potency Test Strategy For Iv Admixtures Prepared By Robotic Systems, Fang Zhao, Vivek S. Dave, Susan E. Hughes 2015 St. John Fisher University

A Modified Potency Test Strategy For Iv Admixtures Prepared By Robotic Systems, Fang Zhao, Vivek S. Dave, Susan E. Hughes

Pharmacy Faculty/Staff Publications

Introduction:

Robotic systems are increasingly used for compounding sterile IV admixtures (1-5). In addition to routine gravimetric checks, initial and periodic drug potency analysis by high-performance liquid chromatography (HPLC) is desired to verify the system accuracy. However, the conventional HPLC test procedures often result in unexpected failures (1-2).

This study was initiated to develop a modified HPLC test strategy to eliminate the common source of variability and focus the effort on the accuracy of robotic system.


Effect Of Biofield Treatment On Spectral Properties Of Paracetamol And Piroxicam, Mahendra Kumar Trivedi, Shrikant Patil, Harish Shettigar, Khemraj Bairwa, Snehasis Jana 2015 Trivedi Global Inc.

Effect Of Biofield Treatment On Spectral Properties Of Paracetamol And Piroxicam, Mahendra Kumar Trivedi, Shrikant Patil, Harish Shettigar, Khemraj Bairwa, Snehasis Jana

Mahendra Kumar Trivedi

Paracetamol and piroxicam are non-steroidal anti-inflammatory drugs (NSAIDs), widely used in pain and inflammatory diseases. The present study aimed to evaluate the impact of biofield treatment on spectral properties of paracetamol and piroxicam. The study was performed in two groups (control and treatment) of each drug. The control groups remained as untreated, and biofield treatment was given to treatment groups. Subsequently, spectral properties of both drugs before and after biofield treatment were characterized using FT-IR and UV-Vis spectroscopic techniques. FT-IR data of paracetamol showed N-H amide II bending peak in biofield treated paracetamol, which was shifted to lower wavenumber (1565 …


Molecular Overlap In The Regulation Of Sk Channels By Small Molecules And Phosphoinositides, Miao Zhang, Xuan-Yu Meng, Ji-fang Zhang, Meng Cui, Diomedes E. Logothetis 2015 Chapman University

Molecular Overlap In The Regulation Of Sk Channels By Small Molecules And Phosphoinositides, Miao Zhang, Xuan-Yu Meng, Ji-Fang Zhang, Meng Cui, Diomedes E. Logothetis

Pharmacy Faculty Articles and Research

Phosphatidylinositol 4,5-bisphosphate (PIP2) directly interacts with the small-conductance Ca2+-activated K+ 2-a (SK2-a) channel/calmodulin complex, serving as a critical element in the regulation of channel activity. We report that changes of protein conformation in close proximity to the PIP2 binding site induced by a small-molecule SK channel modulator, NS309, can effectively enhance the interaction between the protein and PIP2 to potentiate channel activity. This novel modulation of PIP2 sensitivity by small-molecule drugs is likely not to be limited in its application to SK channels, representing an intriguing strategy to develop drugs controlling the activity of the large number of PIP2-dependent proteins.


Interprofessional Research Guidelines: A Community Research Consortium Approach To Implementing Research, Deborah Poling, Kimberly Beran-Shepler, Linda finke, Meg Wilson 2015 Indiana University - Purdue University Fort Wayne

Interprofessional Research Guidelines: A Community Research Consortium Approach To Implementing Research, Deborah Poling, Kimberly Beran-Shepler, Linda Finke, Meg Wilson

Linda M. Finke

No abstract provided.


Editorial: Phosphoinositides And Their Phosphatases: Linking Electrical And Chemical Signals In Biological Processes, Susy C. Kohout, Carlos A. Villalba-Galea 2015 Montana State University-Bozeman

Editorial: Phosphoinositides And Their Phosphatases: Linking Electrical And Chemical Signals In Biological Processes, Susy C. Kohout, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

No abstract provided.


A Study Of 5-Aminolevulinic Acid And Its Methyl Ester Used In In Vitro And In Vivo Systems Of Human Bladder Cancer, Vanaja Manivasager, Paul Wan Sia Heng, Jinsong Hao, Wei Zheng, Khee Chee Soo, Malini Olivo 2015 Marshall University

A Study Of 5-Aminolevulinic Acid And Its Methyl Ester Used In In Vitro And In Vivo Systems Of Human Bladder Cancer, Vanaja Manivasager, Paul Wan Sia Heng, Jinsong Hao, Wei Zheng, Khee Chee Soo, Malini Olivo

Jinsong Hao

The use of 5-aminolevulinic acid and its esters to induce endogenous porphyrins for the purpose of detection of epithelial cancers is being studied extensively in many centres around the world. The challenge is to prepare an efficacious formulation for the purpose of cancer detection. Photodynamic diagnosis of cancer using 5-aminolevulinic acid (ALA) and its ester derivatives is being actively investigated. In this study, we compared ALA with ALA methyl ester (AME) derivative in terms of PpIX fluorescence intensity in in vitro and in vivo systems of bladder carcinoma. For the in vivo system consisting of RT112 xenografts, the modes of …


Research Proposal: Emrs Changing Patient Medication Errors, Kerry Moore 2015 University of Tennessee Health Science Center

Research Proposal: Emrs Changing Patient Medication Errors, Kerry Moore

Applied Research Projects

In 2009 the federal government initiated the American Recovery and Reinvestment Act (ARRA) in efforts to improve timely and quality health care. This new initiative promised to provide great incentives to health care providers who took advantage of the program by implementing electronic medical records (EMRs) within their facilities, clinics, and practices. Coupled with tight deadlines and the incentive of reimbursement, the health care world has been witness to an influx of EMRs being developed by vendors and implemented at health care facilities. The rate at which these EMRs have been implemented has been astounding. So fast, the health care …


Influence Of Linker Length And Composition On Enzymatic Activity And Ribosomal Binding Of Neomycin Dimers, Derrick Watkins, Sunil Kumar, Keith D. Green, Dev P. Arya, Sylvie Garneau-Tsodikova 2015 Nubad LLC

Influence Of Linker Length And Composition On Enzymatic Activity And Ribosomal Binding Of Neomycin Dimers, Derrick Watkins, Sunil Kumar, Keith D. Green, Dev P. Arya, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

The human and bacterial A site rRNA binding as well as the aminoglycoside-modifying enzyme (AME) activity against a series of neomycin B (NEO) dimers is presented. The data indicate that by simple modifications of linker length and composition, substantial differences in rRNA selectivity and AME activity can be obtained. We tested five different AMEs with dimeric NEO dimers that were tethered via triazole, urea, and thiourea linkages. We show that triazole-linked dimers were the worst substrates for most AMEs, with those containing the longer linkers showing the largest decrease in activity. Thiourea-linked dimers that showed a decrease in activity by …


Inhibition Of Aminoglycoside Acetyltransferase Resistance Enzymes By Metal Salts, Yijia Li, Keith D. Green, Brooke R. Johnson, Sylvie Garneau-Tsodikova 2015 University of Kentucky

Inhibition Of Aminoglycoside Acetyltransferase Resistance Enzymes By Metal Salts, Yijia Li, Keith D. Green, Brooke R. Johnson, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

Aminoglycosides (AGs) are clinically relevant antibiotics used to treat infections caused by both Gram-negative and Gram-positive bacteria, as well as Mycobacteria. As with all current antibacterial agents, resistance to AGs is an increasing problem. The most common mechanism of resistance to AGs is the presence of AG-modifying enzymes (AMEs) in bacterial cells, with AG acetyltransferases (AACs) being the most prevalent. Recently, it was discovered that Zn2+ metal ions displayed an inhibitory effect on the resistance enzyme AAC(6')-Ib in Acinetobacter baumannii and Escherichia coli. In this study, we explore a wide array of metal salts (Mg2+, …


Examining Pharmacy Students’ Perceptions Of Clinical Faculty Mentoring Characteristics Influencing Students’ Decision To Pursue A Pharmacy Residency, Kin S. Ly 2015 University of New England

Examining Pharmacy Students’ Perceptions Of Clinical Faculty Mentoring Characteristics Influencing Students’ Decision To Pursue A Pharmacy Residency, Kin S. Ly

All Theses And Dissertations

The field of pharmacy is changing from a drug-distribution-centered model to a patient-centered integrated model whereby pharmacists are actively involved in patient care as part of an interdisciplinary team. To address the estimated pharmacy leadership crisis in the future and to prepare pharmacists to work in the changing healthcare landscape, national pharmacy organizations such as the American Society of Health-System Pharmacists (ASHP) and the American College of Clinical Pharmacy (ACCP) have stated that postgraduate pharmacy residency should be mandatory by 2020. Past pharmacy research literature has shown that while many factors influence students to pursue a pharmacy residency, there is …


The College Of Pharmacy, South Dakota State University 2015 South Dakota State University

The College Of Pharmacy, South Dakota State University

Jackrabbits Script and Scope (Formerly called College of Pharmacy and Allied Health Professions Magazine)

[Page] 2 Master of Public Health College of Pharmacy joins forces with other colleges and USD to offer Master of Public Health degree.
[Page] 4 Father of Tamoxifen V. Craig Jordan visits State as Francis Miller Distinguished Lecturer.
[Page] 6 Hometown satisfaction Dedication to hometown and residents earns Travis Anderberg ’04 the 2015 South Dakota Retailer of the Year.
[Page] 10 Excellence Tadd Hellwig named college’s outstanding scholar while Debra Farver chosen college’s teacher of the year.
[Page] 12 Building better mouse models Markl Faculty Scholar Wenfeng An’s research using mouse models lands two National Institutes of Health grants.
[Page] …


Intractable Delay And The Need To Amend The Petition Provisions Of The Fdca, Diana R. H. Winters 2015 Indiana University Robert H. McKinney School of Law

Intractable Delay And The Need To Amend The Petition Provisions Of The Fdca, Diana R. H. Winters

Indiana Law Journal

Private party oversight has proven to be ineffective at countering inaction by the Food and Drug Administration (FDA). Inaction when regulation is warranted can put the public at continued and increasing risk of harm, but the failure of private enforcement to compel action reverberates beyond this harm to the interests of individuals. It also diminishes the transparency of agency decision making, lessens the opportunity for public participation, and reduces the interaction between the institutions that oversee agencies. Moreover, the benefits afforded to the administrative process by judicial review are weakened.

This Article analyzes two examples of FDA inertia and compares …


New Approach To Develop Ultra-High Inhibitory Drug Using The Power Function Of The Stoichiometry Of The Targeted Nanomachine Or Biocomplex, Dan Shu, Fengmei Pi, Chi Wang, Peng Zhang, Peixuan Guo 2015 University of Kentucky

New Approach To Develop Ultra-High Inhibitory Drug Using The Power Function Of The Stoichiometry Of The Targeted Nanomachine Or Biocomplex, Dan Shu, Fengmei Pi, Chi Wang, Peng Zhang, Peixuan Guo

Pharmaceutical Sciences Faculty Publications

AIMS: To find methods for potent drug development by targeting to biocomplex with high copy number.

METHODS: Phi29 DNA packaging motor components with different stoichiometries were used as model to assay virion assembly with Yang Hui's Triangle [Formula: see text], where Z = stoichiometry, M = drugged subunits per biocomplex, p and q are the fraction of drugged and undrugged subunits in the population.

RESULTS: Inhibition efficiency follows a power function. When number of drugged subunits to block the function of the complex K = 1, the uninhibited biocomplex equals q(z), demonstrating the multiplicative effect of stoichiometry on inhibition with …


Research News. Publications, 2015. Volume 1, University of Mississippi. School of Pharmacy, Soumyajit Majumdar 2015 University of Mississippi

Research News. Publications, 2015. Volume 1, University Of Mississippi. School Of Pharmacy, Soumyajit Majumdar

Publications (2015-)

Publications that appeared during the period January 1 through June 30, 2015


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