Medicine and Health Sciences Commons^™

Synthesis And Evaluation Of Conformationally Constrained Peptide Analogues As The Src Sh3 Domain Binding Ligands, Rakesh Tiwari, Alex Brown, Seetha Narramaneni, Gongqin Sun, Keykavous Parang

Pharmacy Faculty Articles and Research

Src kinase activity is regulated by the interaction of SH3 domain with protein sequences that are rich in proline residues. Identification of more potent SH3 domain binding ligands that can regulate Src kinase activity is a subject of major interest. Conformationally constrained peptides have been previously used for improving the binding potency of the Src SH2 domain binding peptide ligands and peptide substrates of the substrate-binding site of Src. A series of peptide analogues of Ac-VSLARRPLPPLP (1, Ac-VSL-12, Kd = 0.34 M) were synthesized by introducing conformational constraints to improve the binding affinity towards the Src SH3 domain. Peptides synthesized …

Efficacy And Safety Of Mitomycin C As An Agent To Treat Corneal Scarring In Horses Using An In Vitro Model, Dylan G. Buss, Ajay Sharma, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—Mitomycin C (MMC) is used clinically to treat corneal scarring in human patients. We investigated the safety and efficacy of MMC to treat corneal scarring in horses by examining its effects at the early and late stages of disease using an in-vitro model.

Procedure—An in-vitro model of equine corneal fibroblast (ECF) developed was used. The equine corneal fibroblast or myofibroblast cultures were produced by growing primary ECF in the presence or absence of transforming growth factor beta-1 (TGFβ1) under serum-free conditions. The MMC dose for the equine cornea was defined with dose-dependent trypan blue exclusion and MTT [(3-4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays …

Prospects And Pits On The Path Of Biomimetics: The Case Of Tooth Enamel, Vuk Uskoković

Pharmacy Faculty Articles and Research

This review presents a discourse on challenges in understanding and imitating the process of amelogenesis in vitro on the molecular scale. In light of the analysis of imitation of the growth of dental enamel, it also impends on the prospects and potential drawbacks of the biomimetic approach in general. As the formation of enamel proceeds with the protein matrix guiding the crystal growth, while at the same time conducting its own degradation and removal, it is argued that three aspects of amelogenesis need to be induced in parallel: a) crystal growth; b) protein assembly; c) proteolytic degradation. A particular emphasis …

Isolation And Cultivation Of Equine Corneal Keratocytes, Fibroblasts And Myofibroblasts, Dylan G. Buss, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To establish an in vitro model for the investigation of equine corneal wound healing. To accomplish this goal, a protocol to isolate and culture equine corneal keratocytes, fibroblasts and myofibroblasts was developed.

Animal material—Equine corneal buttons were aseptically harvested from healthy research horses undergoing humane euthanasia for reasons unrelated to this study. Slit-lamp biomicroscopy was performed prior to euthanasia by a board-certified veterinary ophthalmologist to ensure that all samples were harvested from horses free of anterior segment disease.

Procedure—Equine corneal stroma was isolated using mechanical techniques and stromal subsections were then cultured. Customized media at different culture conditions was used …

Localization Of Angiotensin Converting Enzyme In Rabbit Cornea And Its Role In Controlling Corneal Angiogenesis In Vivo, Ajay Sharma, Daniel I. Bettis, John W. Cowden, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: The renin angiotensin system (RAS) has been shown to modulate vascular endothelial growth factor and angiogenesis. In this study we investigated (i) the existence of the RAS components angiotensin converting enzyme (ACE) and angiotensin II receptors (AT1 and AT2) in the rabbit cornea using in vitro and ex vivo models and (ii) the effect of enalapril, an ACE inhibitor, to inhibit angiogenesis in rabbit cornea in vivo.

Methods: New Zealand White rabbits were used. Cultured corneal fibroblasts and corneal epithelial cells were used for RNA isolation and cDNA preparation using standard molecular biology techniques. PCR was performed to …

The Nonpsychoactive Cannabinoid Cannabidiol Inhibits 5-Hydroxytryptamine3a Receptor-Mediated Currents In Xenopus Laevis Oocytes, Keun-Hang Susan Yang, Sehamuddin Galadari, Dmytro Isaev, Georg Petroianu, Toni S. Shippenberg, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

The effect of the plant-derived nonpsychotropic cannabinoid, cannabidiol (CBD), on the function of hydroxytryptamine (5-HT)3A receptors expressed in Xenopus laevis oocytes was investigated using two-electrode voltage-clamp techniques. CBD reversibly inhibited 5-HT (1 μM)-evoked currents in a concentration-dependent manner (IC50 = 0.6 μM). CBD (1 μM) did not alter specific binding of the 5-HT3A antagonist [3H]3-(5-methyl-1H-imidazol-4-yl)-1-(1-methylindol-3-yl)propan-1-one (GR65630), in oocytes expressing 5-HT3A receptors. In the presence of 1 μM CBD, the maximal 5-HT-induced currents were also inhibited. The EC50 values were 1.2 and 1.4 μM, in the absence and presence of CBD, indicating that CBD acts as a noncompetitive antagonist of 5-HT3 …

Chemosensitization Of Cancer Cells By Sirna Using Targeted Nanogel Delivery, Erin B. Dickerson, William H. Blackburn, Michael H. Smith, Laura B. Kapa, L. Andrew Lyon, John F. Mcdonald

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Background: Chemoresistance is a major obstacle in cancer treatment. Targeted therapies that enhance cancer cell sensitivity to chemotherapeutic agents have the potential to increase drug efficacy while reducing toxic effects on untargeted cells. Targeted cancer therapy by RNA interference (RNAi) is a relatively new approach that can be used to reversibly silence genes in vivo by selectively targeting genes such as the epidermal growth factor receptor (EGFR), which has been shown to increase the sensitivity of cancer cells to taxane chemotherapy. However, delivery represents the main hurdle for the broad development of RNAi therapeutics.

Methods: We report here …

Rhabdomyolysis, Hypothyroidism, And Fatty Acid Oxidation: More Related Than You Think, Jeanne Zukas Do

Department of Medicine

No abstract provided.

The Complication Of Migration: To Place Or Not To Place An Inferior Vena Cava Filter?, Courtney Bennett Do, Stacey Smith Md

Department of Medicine

No abstract provided.

Diabetes Mellitus Self-Management: Comparison Of Curricula Using A Promotora, Francigna Rodriguez Bs, Nyann Biery Ms, Cathy Coyne Phd, Robert Motley Md, Edgar Maldonado Md, Abby S. Letcher Md

Department of Medicine

No abstract provided.

A Three Tiered Model Of Maternity Care Training, Holly Binnig Md

Department of Medicine

No abstract provided.

Effect Of The Tyrosine Kinase Inhibitors (Sunitinib, Sorafenib, Dasatinib, And Imatinib) On Blood Glucose Levels In Diabetic And Non-Diabetic Patients In General Clinical Practice (Poster), Nicole M. Agostino Do, Vernon M. Chinchilli Phd, Christopher J. Lynch Phd, Anita M. Koszyk-Szewczyk Md, Rebecca Gingrich Rn, Ms, Ocn, Jeffery Sivik D Pharma, Joseph J. Darbick Md, Facp

Department of Medicine

No abstract provided.

Glucocorticoid-Remediable Aldosteronism: An Uncommon And Often Overlooked Cause Of Adrenal Hypertension, Sindhu Bhat Md, Larry N. Merkle Md

Department of Medicine

No abstract provided.

Incorporating Rehabilitation Services Into Oncology Site-Specific Clinical Practice Guidelines, Kathleen Leies Rn, Ocn, Kathy Sevedge Rn, Ma, Aocn, Dorothy Morrone Rnc, Ms, Ocn, Stephanie Marshall Ccer, Jennifer Roeder Mspt, Mba

Department of Medicine

No abstract provided.

When You Hear Hoof Beats, It Might Be A Zebra: Lupus Patient With Fever And Leukopenia, Erica Peart Do, James Ross Md, Facp

Department of Medicine

No abstract provided.

In Vitro Application Of Gold Nanoprobes In Live Neurons For Phenotypical Classification, Connectivity Assessment, And Electrophysiological Recording, Karl C. Mendoza

Dissertations, Theses, and Masters Projects

No abstract provided.

Surviving Myxedema Coma In A Patient With Previously Undiagnosed Hypothyroidism, Shadi Jarjous Md

Department of Medicine

No abstract provided.

Impact Of Static Stretch And Muscular Contractions On Force Production Within The Human Triceps Surae Muscle-Tendon Complex, Anthony D. Kay

Theses: Doctorates and Masters

Pre-performance routines commonly include stretching and intense muscular contractions in an attempt to optimise muscular performance and reduce injury risk. However, the isolated and combined effects of stretching and muscle contractions on neuromuscular performance are not well described. The aims of this research were to examine the effects of acute static stretch and intense muscular contractions on force production of the human plantarflexors and to examine possible mechanical and neuromuscular mechanisms underpinning any changes. Techniques including isokinetic dynamometry, electromyography (EMG), sonography and motion analysis were used in three studies on recreationally active human volunteers (n=20). In the first study, three …

Lifting Without Seeing: The Role Of Vision In Perceiving And Acting Upon The Size Weight Illusion, Gavin Buckingham, Melvyn Goodale

Gavin Buckingham

BACKGROUND: Our expectations of an object's heaviness not only drive our fingertip forces, but also our perception of heaviness. This effect is highlighted by the classic size-weight illusion (SWI), where different-sized objects of identical mass feel different weights. Here, we examined whether these expectations are sufficient to induce the SWI in a single wooden cube when lifted without visual feedback, by varying the size of the object seen prior to the lift.

METHODOLOGY/PRINCIPAL FINDINGS: Participants, who believed that they were lifting the same object that they had just seen, reported that the weight of the single, standard-sized cube that they …

The Relation Of Aerobic Fitness To Neuroelectric Indices Of Cognitive And Motor Task Preparation, Jason Themanson, Keita Kamijo, Kevin O'Leary, Matthew Pontifex, Charles Hillman

Jason R. Themanson, Ph.D

The relation of aerobic fitness to task preparation was examined in a sample of young adults separated into higher- and lower-fit groups according to their maximal oxygen consumption. Participants performed a modified Sternberg working memory task under speed and accuracy instructions while measures of task performance and contingent negative variation (CNV) were collected. Analyses revealed no significant fitness differences between groups on task performance measures. However, frontal CNVamplitude was significantly larger for lower-fit participants compared to higher-fit participants during the speed instructions, an effect not found for the accuracy instructions. These results suggest that lower-fit individuals may rely to a …

Measuring The Hiv/Aids Epidemic: Approaches And Challenges, Ron Brookmeyer

Ron Brookmeyer

In this article, the author reviews current approaches and methods for measuring the scope of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic and their strengths and weaknesses. In recent years, various public health agencies have revised statistical estimates of the scope of the HIV/AIDS pandemic. The author considers the reasons underlying these revisions. New sources of data for estimating HIV prevalence have become available, such as nationally representative probability-based surveys. New technologies such as biomarkers that indicate when persons became infected are now used to determine HIV incidence rates. The author summarizes the main sources of errors and …

Lifting Without Seeing: The Role Of Vision In Perceiving And Acting Upon The Size‐Weight Illusion, Gavin Buckingham, Melvyn Goodale

Gavin Buckingham

Our expectations of an object’s heaviness not only drive our fingertip forces, but also our perception of heaviness. This effect is highlighted by the classic size-weight illusion (SWI), where different‐sized objects of identical mass feel different weights (Charpentier, 1891) long after any initial errors in the application of fingertip forces have been corrected (Flanagan & Beltzner, 2000).

Here, we examined whether our expectations about the weight of an upcoming lift are sufficient to induce the SWI in a single wooden cube when lifted without visual feedback, by varying the size of the object seen prior to the lift during a …

Laterality, Perception, And Action During The Size-Weight Illusion, Gavin Buckingham, Nathalie Ranger, Melvyn Goodale

Gavin Buckingham

In the classic size-weight illusion (SWI), a small object will feel heavier than an larger object of equal weight (Charpentier, 1891). Individuals continue to perceive this illusory difference in weight long after their gripping and lifting forces have scaled to the actual, identical, mass of the illusion-inducing stimuli (Flanagan & Beltzner, 2000).

The independence of our weight perception and fingertip force application has only been quantified in the right hand of right-handers. The immunity to this perceptual illusion may be affected by manual asymmetries (e.g., Gonzalez, Ganel & Goodale, 2006).

We examined perception of heaviness and fingertip force scaling in …

Ganaxolone Suppression Of Behavioral And Electrographic Seizures In The Mouse Amygdala Kindling Model, Doodipala S. Reddy, Michael A. Rogawski

Michael A. Rogawski

Ganaxolone (3alpha-hydroxy-3alpha-methyl-5alpha-pregnan-20-one), a synthetic analog of the endogenous neurosteroid allopregnanolone and a positive allosteric modulator of GABA-A receptors, may represent a new treatment approach for epilepsy. Here we demonstrate that pretreatment with ganaxolone (1.25—20 mg/kg, s.c.) causes a dose-dependent suppression of behavioral and electrographic seizures in fully amygdala-kindled female mice, with nearly complete seizure protection at the highest dose tested. The ED50 for suppression of behavioral seizures was 6.6 mg/kg. The seizure suppression produced by ganaxolone was comparable to that of clonazepam (ED50, 0.1 mg/kg, s.c.). To the extent that amygdala kindling represents a model of mesial temporal lobe epilepsy, …

Neurosteroids On The Epilepsy Chessboard — Keeping Seizures In Check, Michael A. Rogawski

Michael A. Rogawski

No abstract provided.

Treatment Of Early And Late Kainic-Acid Induced Status Epilepticus With The Non-Competitive Ampa Receptor Antagonist Gyki 52466, Brita Fritsch, Jeffrey J. Stott, J. Joelle Donofrio, Michael A. Rogawski

Michael A. Rogawski

Purpose: Benzodiazepines such as diazepam may fail to effectively treat status epilepticus because benzodiazepine-sensitive GABA-A receptors are internalized progressively with continued seizure activity. Ionotropic glutamate receptors, including AMPA receptors, are externalized, so that AMPA receptor antagonists, which are broad-spectrum anticonvulsants, could be more effective treatments for satus epilepticus. We assessed the ability of the non-competitive AMPA receptor antagonist GYKI 52466 to protect against kainic acid-induced status epilepticus in mice. Methods: Groups of animals treated with kainic acid received GYKI 52466 (50 mg/kg followed in 15 min by 50 mg/kg) or diazepam (25 mg/kg followed in 20 min by 12.5 mg/kg) …

Anticonvulsant And Proconvulsant Actions Of 2-Deoxy-D-Glucose, Maciej Gasior, Jessica Yankura, Adam L. Hartman, Amy French, Michael A. Rogawski

Michael A. Rogawski

Purpose: 2-Deoxy-D-glucose (2-DG), a glucose analog that accumulates in cells and interferes with carbohydrate metabolism by inhibiting glycolytic enzymes, has anticonvulsant actions. Recognizing that severe glucose deprivation can induce seizures, we sought to determine whether acute treatment with 2-DG can promote seizure susceptibility by assessing its effects on seizure threshold. For comparison, we studied 3-methyl-glucose (3-MG), which like 2-DG accumulates in cells and reduces glucose uptake, but does not inhibit glycolysis. Methods: Mice were treated with 2-DG or 3-MG and the seizure threshold determined in the 6-Hz test, the mouse electroshock seizure threshold (MEST) test, and the intravenous pentylenetetrazol (i.v. …

On The Statistical Accuracy Of Biomarker Assays Of Hiv Incidence, Ron Brookmeyer

Ron Brookmeyer

Objective: To evaluate the statistical accuracy of estimates of current HIV incidence rates from cross-sectional surveys, and to identify characteristics of assays that improve accuracy.

Methods: Performed mathematical and statistical analysis of the cross-sectional estimator of HIV incidence to evaluate bias and variance. Developed probability models to evaluate impact of long tails of the window period distribution on accuracy.

Results: The standard cross-sectional estimate of HIV incidence rate is estimating a time-lagged incidence where the lag time, called the shadow, depends on the mean and the coefficient of variation of window periods. Equations show how the shadow increases with the …

Semiparametric Analysis Of Recurrent Events: Artificial Censoring, Truncation, Pairwise Estimation And Inference, Debashis Ghosh

Debashis Ghosh

The analysis of recurrent failure time data from longitudinal studies can be complicated by the presence of dependent censoring. There has been a substantive literature that has developed based on an artificial censoring device. We explore in this article the connection between this class of methods with truncated data structures. In addition, a new procedure is developed for estimation and inference in a joint model for recurrent events and dependent censoring. Estimation proceeds using a mixed U-statistic based estimating function approach. New resampling-based methods for variance estimation and model checking are also described. The methods are illustrated by application to …