Chemicals and Drugs Commons^™

A Human Phospholipid Phosphatase Activated By A Transmembrane Control Module, Christian R. Halaszovich, Michael G. Leitner, Angeliki Mavrantoni, Audrey Le, Ludivine Frezza, Anja Feuer, Daniela N. Schreiber, Carlos A. Villalba-Galea, Dominik Oliver

School of Pharmacy Faculty Articles

In voltage-sensitive phosphatases (VSPs), a transmembrane voltage sensor domain (VSD) controls an intracellular phosphoinositide phosphatase domain, thereby enabling immediate initiation of intracellular signals by membrane depolarization. The existence of such a mechanism in mammals has remained elusive, despite the presence of VSP-homologous proteins in mammalian cells, in particular in sperm precursor cells. Here we demonstrate activation of a human VSP (hVSP1/TPIP) by an intramolecular switch. By engineering a chimeric hVSP1 with enhanced plasma membrane targeting containing the VSD of a prototypic invertebrate VSP, we show that hVSP1 is a phosphoinositide-5-phosphatase whose predominant substrate is PI(4,5)P(2). In the chimera, enzymatic activity …

The Role Of The Yxxφ Motif In Cd82 Trafficking And Function, Mekel Marie Richardson

Theses and Dissertations (ETD)

CD82, a tetraspanin, is a tumor metastasis suppressor. Tetraspanins are membrane spanning proteins that play critical roles in diverse biological and pathological processes, e.g., the regulation of cancer metastasis. CD82 is ubiquitously expressed in various types of tissues, but its expression becomes down-regulated or lost in a majority of metastatic tumors. It inhibits tumor metastasis without affecting primary tumor growth. Cancer patients whose tumors contain CD82 exhibit minimal metastasis. We know that CD82 functions as a tumor metastasis suppressor but the mechanism by which this occurs is largely unknown. CD82 can be found on the plasma membrane as well as …

The Effects Of Supplemental Fish Oil On Blood Pressure And Morning Cortisol In Normotensive Adults: A Pilot Study, Eric E. Noreen, Josef Brandauer

Health Sciences Faculty Publications

Purpose: To determine the effects of 6wk of supplementation with fish oil (FO) on blood pressure and the morning salivary cortisol concentration in normotensive adults.

Methods: Testing was performed following an overnight fast. Subjects (n=40; 35+/-13y, mean+/-SD) rested supine for 40 min, at which time blood pressure and heart rate were measured. Saliva was collected and analyzed for cortisol. Subjects were then randomly assigned to either: 4g/d of Safflower Oil (SO); pr 4g/d of FO supplying 1,600mg/d eicosapentaenoic acid and 800mg/d docosahexaenoic acid. Testing was repeated following 6wk treatment.

Results: Compared to SO, there was a significant decrease …

Situation Analysis Of Child Labour In Karachi, Pakistan: A Qualitative Study, Asaad Ahmed Nafees, Kausar S. Khan, Zafar Fatmi, Mubashir Aslam

Community Health Sciences

In Karachi, large employment opportunities, burgeoning population and the availability of cheap labour might be the contributing factors for the increasing prevalence of child labour. A literature review was conducted in 2007 that included published and unpublished literature since 2000. Various organizations working in the field were also covered, while the perception of the child labourers was covered through three focus group discussions. Common health issues among the child labourers in Karachi included respiratory illnesses, fever and generalised pains, as well as drug and sexual abuse. Organisations working for child labour could be broadly categorised into those working for legal …

Drug–Drug Conditioning Between Citalopram And Haloperidol Or Olanzapine In A Conditioned Avoidance Response Model: Implications For Polypharmacy In Schizophrenia, Nathan L. Sparkman, Ming Li

Department of Psychology: Faculty Publications

Patients with schizophrenia often have anxiety and depression, and thus are treated with multiple psychotherapeutic medications. This practice of polypharmacy increases the possibility for drug–drug interactions. However, the pharmacological and behavioral mechanisms underlying drug–drug interactions in schizophrenia remain poorly understood. In the present study, we adopted a preclinical approach and examined a less known behavioral mechanism, drug–drug conditioning (DDC) between haloperidol (a typical antipsychotic) or olanzapine (atypical antipsychotic) and citalopram (a selective serotonin reuptake inhibitor). A rat two-way conditioned avoidance response paradigm was used to measure antipsychotic activity and determine how DDC may alter the antipsychotic efficacy in this model. …

Edible Marijuana: A New Frontier In The Culinary World, Ariella H. Wolkowicz

Honors Theses - Providence Campus

Cannabis, commonly known as marijuana, has a rich history as a source of fiber, food and medicine (Li 437). Since 1785, physicians and scientists alike have worked to discover the active chemical components and medical effectiveness of this plant (Touw 2; Aldrich). Despite its complicated legal history, marijuana has retained a place culturally and, in some countries, scientifically as an effective medical agent. As a medically edible ingredient, cannabis has also been more recently heralded as a new, even cutting edge flavor, opening a new frontier to the culinary community.

After the isolation of the main active ingredient in cannabis, …

Pediatric Pharmacogenomics: A Systematic Assessment Of Ontogeny And Genetic Variation To Guide The Design Of Statin Studies In Children., Jonathan B. Wagner, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

The dose-exposure-response relationship for drugs may differ in pediatric patients compared with adults. Many clinical studies have established drug dose-exposure relationships across the pediatric age spectrum; however, genetic variation was seldom included. This article applies a systematic approach to determine the relative contribution of development and genetic variation on drug disposition and response using HMG-CoA reductase inhibitors as a model. Application of the approach drives the collection of information relevant to understanding the potential contribution of ontogeny and genetic variation to statin dose-exposure-response in children, and identifies important knowledge deficits to be addressed through the design of future studies.

Voltage-Controlled Enzymes: The New Janus Bifrons, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The Ciona intestinalis voltage-sensitive phosphatase, Ci-VSP, was the first Voltage-controlled Enzyme (VEnz) proven to be under direct command of the membrane potential. The discovery of Ci-VSP conjugated voltage sensitivity and enzymatic activity in a single protein. These two facets of Ci-VSP activity have provided a unique model for studying how membrane potential is sensed by proteins and a novel mechanism for control of enzymatic activity. These facets make Ci-VSP a fascinating and versatile enzyme. Ci-VSP has a voltage sensing domain (VSD) that resembles those found in voltage-gated channels (VGC). The VSD resides in the N-terminus and is formed by four …

Obtaining A Pure Protein Using An Elp-Tagged Tev Protease, Teisha L. Mullins

Undergraduate Research Posters 2012

We present here use of GLGVP for tagging and purifying a gadolinium binding protein domain.

Understanding The Structure Of High Density Lipoprotein, Dmitriy Parshakov, Kayla T. Tran

Undergraduate Research Posters 2012

The high-density lipoprotein (HDL), the carrier of ‘good cholesterol’, transports cholesterol from periphery cells to liver for catabolism, a process termed reverse cholesterol transport. In this project we focused on obtaining and characterizing HDL particles.

Key Players In Reverse Cholesterol Transport: The Plasma Enzyme Lcat, Christopher J. Pechura

Undergraduate Research Posters 2012

Lecithin cholesterol acyltransferase (LCAT) is a plasma enzyme that remodels nascent high density lipoprotein (HDL) into a mature form called spherical HDL. The model will be used in the future to map the amino acid residues from LCAT and the protein component of nascent HDL (apoA1) involved in mutual interaction, and to identify LCAT residues interacting with the lipid phase of nascent HDL.

Biological Evaluation Of Cyclooxygenase-2 Inhibitor Nimesulide Derivatives As Anti-Agents, Amandeep Singh, Snigdha Chennamaneni

Undergraduate Research Posters 2012

Cyclooxygenase-2 (COX-2) inhibitor nimesulide inhibits the proliferation of various types of cancer cells mainly via COX-2 independent mechanisms, which makes it a good lead compound for anti-cancer drug development. A series of new nimesulide analogs were evaluated with cell proliferation assay based on a non-small lung cancer cell line H292. The results showed that several derivatives were very active to against H292 cell growth with IC50s of sub nano mole. These results suggest the possibility of using these nimesulide derivatives as chemo preventive agents.

Borrelia Burgdorferi Cp32 Bpab Modulates Expression Of The Prophage Nucp Nuclease And Ssbp Single-Stranded Dna-Binding Protein, Alicia M. Chenail, Brandon L. Jutras, Claire A. Adams, Logan H. Burns, Amy Bowman, Ashutosh Verma, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Borrelia burgdorferi BpaB proteins of the spirochete's ubiquitous cp32 prophages are DNA-binding proteins, required both for maintenance of the bacteriophage episomes and for transcriptional regulation of the cp32 erp operons. Through use of DNase I footprinting, we demonstrate that BpaB binds the erp operator initially at the sequence 5′-TTATA-3′. Electrophoretic mobility shift assays indicated that BpaB also binds with high affinity to sites located in the 5′ noncoding regions of two additional cp32 genes. Characterization of the proteins encoded by those genes indicated that they are a single-stranded DNA-binding protein and a nuclease, which we named SsbP and NucP, …

Human Endometrial Stromal Stem Cells Differentiate Into Megakaryocytes With The Ability To Produce Functional Platelets, Jinju Wang, Shuzhen Chen, Cheng Zhang, Samantha Stegeman, Teresa Pfaff-Amesse, Ying Zhang, Wenfeng Zhang, Lawrence Amesse, Yanfang Chen

Pharmacology and Toxicology Faculty Publications

Human endometrium is a high dynamic tissue that contains endometrial stromal stem cells (hESSCs). The hESSCs have been differentiated into a number of cell lineages. However, differentiation of hESSCs into megakaryocytes (MKs) has not yet been investigated. The aim of this study was to investigate the feasibility of MK generation from hESSCs and subsequent production of functional platelets (PLTs). In our study, hESSCs were cultured from endometrial stromal cells as confirmed by positive stromal cell specific markers (CD90 and CD29) and negative hematopoietic stem cell markers (CD45 and CD34) expression. Then, hESSCs were differentiated in a medium supplemented with thrombopoietin …

Development Of A Men’S Preference For Testosterone Replacement Therapy (P-Trt) Instrument, Sheryl L. Szeinbach, Enrique Seoane-Vazquez, Kent H. Summers

Pharmacy Faculty Articles and Research

Background: This study used a standard research approach to create a final conceptual model and the Preference for the Testosterone Replacement Therapy (P-TRT) instrument.

Methods: A discussion guide was developed from a literature review and expert opinion to direct one-on-one interviews with participants who used testosterone replacement therapy and consented to participate in the study. Data from telephone interviews were transcribed for theme analysis using NVivo 9 qualitative analysis software, analyzed descriptively from a saturation grid, and used to evaluate men’s P-TRT. Data from cognitive debriefing for five participants were used to evaluate the final conceptual model and …

Identification Of The Functional Binding Pocket For Compounds Targeting Small-Conductance Ca2+-Activated Potassium Channels, Miao Zhang, John M. Pascal, Marcel Schumann, Roger S. Armen, Ji-Fang Zhang

Pharmacy Faculty Articles and Research

Small- and intermediate-conductance Ca2+-activated potassium channels, activated by Ca2+-bound calmodulin, play an important role in regulating membrane excitability. These channels are also linked to clinical abnormalities. A tremendous amount of effort has been devoted to developing small molecule compounds targeting these channels. However, these compounds often suffer from low potency and lack of selectivity, hindering their potentials for clinical use. A key contributing factor is the lack of knowledge of the binding site(s) for these compounds. Here we demonstrate by X-ray crystallography that the binding pocket for the compounds of the 1-EBIO class is located at the calmodulin-channel interface. We …

Taking Aim At The Start Of Translation, Medha Raina, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

No abstract provided.

Quantification And In Vitro Analysis Of Nanolipoproteins (Nlps) Containing Adjuvants, Purna Venkataraman, Craig Blanchette, Nicholas O. Fischer

STAR Program Research Presentations

Nanolipoprotein particles (NLPs) self-assemble into nanoscale structures that can be used as vaccines or drug delivery agents. Due to the nature of the NLPs, a variety of immune stimulating compounds or adjuvants can be readily incorporated into NLPs: a characteristic difficult to engineer into most other nanoscale platforms. In light of this, a method for quantifying the amount adjuvant actually incorporated into NLPs is a question of high importance. Through the use of reverse phase High-Performance Liquid Chromatography (HPLC) and an Evaporative Light Scattering Detector (ELSD), standard curves can be constructed by analyzing mixtures of NLP components of known concentration, …

Parametric Studies Of Antipsychotic-Induced Sensitization In The Conditioned Avoidance Response Model: Roles Of Number Of Drug Exposure, Drug Dose, And Test–Retest Interval, Natashia Swalve, Ming Li

Department of Psychology: Faculty Publications

Repeated haloperidol and olanzapine treatment produces an enhanced disruption of avoidance responding, a validated measure of antipsychotic activity. Experimental parameters affecting this sensitization-like effect have not been thoroughly examined. The present study investigated the role of three parameters (number of injections, dose, and interval between initial exposure and challenge) in antipsychotic sensitization in the conditioned avoidance response paradigm. Well-trained Sprague–Dawley rats received different numbers of drug treatment (1–5 days) or different doses of haloperidol (0.025–0.10 mg/kg, subcutaneously) or olanzapine (0.5–2.0 mg/kg, subcutaneously). After certain time intervals (4, 10 or 17 days), they were tested for the expression of haloperidol or …

Prolonged Intermediate Syndrome Pue To Prganophosphate Poisoning, Nadeem Ullah Khan, Muhammad Junaid Patel, M. N.M. Hifath, Saima Kamal, Syed Ather Hussain

Department of Emergency Medicine

Organophosphate poisoning can present as acute cholinergic syndrome, Intermediate syndrome and delayed neuropathy. Intermediate syndrome secondary to organophosphate poisoning is a serious health problem leading to increased morbidity and mortality. The incidence of problem varies and range from 8%-84% of organophosphate poisoning cases. The factors account for this difference is nature of organophosphate compound, severity of poisoning and inadequate Oxime therapy. The recognition of this syndrome is important as organophosphate poisoning is common in our country. We presented this case of organophosphate poisoning leading to prolonged intermediate syndrome. The muscle weakness associated with this syndrome generally resolves in 5-18 days …