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Full-Text Articles in Musculoskeletal, Neural, and Ocular Physiology

The Feigned Annoyance And Frustration Test To Activate The Sympathoadrenal Medullary System, Ted W. Gehrig Iii, Lee S. Berk, Robert I. Dudley, Jo A. Smith, Lida Gharibvand, Everett B. Lohman Iii Apr 2024

The Feigned Annoyance And Frustration Test To Activate The Sympathoadrenal Medullary System, Ted W. Gehrig Iii, Lee S. Berk, Robert I. Dudley, Jo A. Smith, Lida Gharibvand, Everett B. Lohman Iii

Physical Therapy Faculty Articles and Research

When perceived as threatening, social interactions have been shown to trigger the sympathoadrenal medullary system as well as the hypothalamic-pituitary-adrenal axis resulting in a physiologic stress response. The allostatic load placed on human health and physiology in the context of acute and chronic stress can have profound health consequences. The purpose of this study was to develop a protocol for a lab-based stress stimulus using social-evaluative threat. While several valid, stress-stimulating protocols exist, we sought to develop one that triggered a physiologic response, did not require significant lab resources, and could be completed in around 10 min. We included 53 …


Local Renin-Angiotensin System Activation And Myofibroblast Formation In Graft Versus Host Disease–Associated Conjunctival Fibrosis, Kiumars Shamloo, Judy Weng, Christopher Ross, Jenni Lee, Saleh Alfuraih, Jennifer Totonchy, Ajay Sharma Oct 2021

Local Renin-Angiotensin System Activation And Myofibroblast Formation In Graft Versus Host Disease–Associated Conjunctival Fibrosis, Kiumars Shamloo, Judy Weng, Christopher Ross, Jenni Lee, Saleh Alfuraih, Jennifer Totonchy, Ajay Sharma

Pharmacy Faculty Articles and Research

Purpose: The present study was designed to investigate the role of myofibroblast transdifferentiation and the conjunctival renin–angiotensin system (RAS) in the pathogenesis of graft-versus-host disease (GVHD)–associated conjunctival fibrosis.

Methods: A mouse model of major histocompatibility-matched allogeneic transplantation was used to induce GVHD, with male B10.D2 mice as donors and female BALB/c mice as recipients. Male BALB/c to female BALB/c syngeneic transplantation was used as control. Y chromosome staining in the spleen cells obtained from female recipient mice was used to confirm engraftment. The phenol red thread test and fluorescein staining were used to quantify tears and corneal keratopathy. …


Dimensionality Reduction For Classification Of Object Weight From Electromyography, Elnaz Lashgari, Uri Maoz Aug 2021

Dimensionality Reduction For Classification Of Object Weight From Electromyography, Elnaz Lashgari, Uri Maoz

Psychology Faculty Articles and Research

Electromyography (EMG) is a simple, non-invasive, and cost-effective technology for measuring muscle activity. However, multi-muscle EMG is also a noisy, complex, and high-dimensional signal. It has nevertheless been widely used in a host of human-machine-interface applications (electrical wheelchairs, virtual computer mice, prosthesis, robotic fingers, etc.) and, in particular, to measure the reach-and-grasp motions of the human hand. Here, we developed an automated pipeline to predict object weight in a reach-grasp-lift task from an open dataset, relying only on EMG data. In doing so, we shifted the focus from manual feature-engineering to automated feature-extraction by using pre-processed EMG signals and thus …


Differential Effect Of Proinflammatory Cytokines On Corneal And Conjunctival Epithelial Cell Mucins And Glycocalyx, Kiumars Shamloo, Priya Mistry, Ashley Barbarino, Christopher Ross, Vishal Jhanji Jun 2021

Differential Effect Of Proinflammatory Cytokines On Corneal And Conjunctival Epithelial Cell Mucins And Glycocalyx, Kiumars Shamloo, Priya Mistry, Ashley Barbarino, Christopher Ross, Vishal Jhanji

Pharmacy Faculty Articles and Research

Purpose: Ocular surface mucins and glycocalyx are critical for providing ocular hydration as well lubrication and repelling pathogens or allergens. Elevated levels of tear proinflammatory cytokines in dry eye may have detrimental effect on mucins and glycocalyx. The present study tested the effect of proinflammatory cytokines IL-6, TNF-α, and IFN-γ on membrane-tethered mucins expression, glycocalyx, and viability of ocular surface epithelial cells.

Methods: Stratified cultures of human corneal and conjunctival epithelial cells were exposed to different concentrations of IL-6, TNF-α, and IFN-γ for 24 hours. The mucins gene and protein expressions were quantified by real-time polymerase chain reaction …


Fluorometholone Modulates Gene Expression Of Ocular Surface Mucins, Jonathan Taniguchi, Ajay Sharma Apr 2019

Fluorometholone Modulates Gene Expression Of Ocular Surface Mucins, Jonathan Taniguchi, Ajay Sharma

Pharmacy Faculty Articles and Research

Purpose

Mucins are vital to keep the ocular surface hydrated. Genes encoding for mucins contain a glucocorticoid response element. The purpose of this study was to evaluate the effect of fluorometholone, a glucocorticoid receptor agonist used in the management of dry eye, on the gene expression of conjunctival and corneal epithelial cell mucins.

Methods

Stratified cultures of human conjunctival and corneal epithelial cells were exposed to 25, 50 and 100 nM of fluorometholone alone or in presence of mifepristone, a glucocorticoid receptor antagonist. The mRNA was isolated from the cells and reverse transcribed to cDNA. The cDNA was used for …


Effects Of Load Carriage And Surface Inclination On Linear And Non-Linear Postural Variability, Rahul Soangra, Hema Bhatt, Ehsan Rashedi Apr 2018

Effects Of Load Carriage And Surface Inclination On Linear And Non-Linear Postural Variability, Rahul Soangra, Hema Bhatt, Ehsan Rashedi

Physical Therapy Faculty Articles and Research

Understanding of inclined-work-related risk of falls and developing novel practical engineering controls for reducing this risk of falls among hilly working population remains in high demand. Standing on sloped surfaces provides a unique environment for examining the biomechanics and neural control of standing. The present investigation examined the variability of postural signals when standing on inclined surfaces and with load carriages by linear and nonlinear analysis. The purpose of this study was to determine if the sloped surface deteriorated in postural stability among healthy individuals with two distinctive kinds of load carriage methods head versus posterior load carriage. We also …


Changes In The Utilization Of Osteoporosis Drugs After The 2010 Fda Bisphosphonate Drug Safety Communication, Bander Balkhi, Enrique Seoane-Vazquez, Rosa Rodriguez-Monguio Dec 2017

Changes In The Utilization Of Osteoporosis Drugs After The 2010 Fda Bisphosphonate Drug Safety Communication, Bander Balkhi, Enrique Seoane-Vazquez, Rosa Rodriguez-Monguio

Pharmacy Faculty Articles and Research

Introduction

In October 2010, the US Food and Drug Administration (FDA) issued a safety communication regarding the risks of atypical fractures of the femur, with bisphosphonates drugs. This study evaluated the impact of the bisphosphonates FDA safety communication on the utilization of osteoporosis medications in Medicaid programs.

Methods

Osteoporosis drugs utilization data from the July 2006 to June 2014 were extracted from the national Summary Files from the Medicaid State Drug Utilization Data maintained by the Centers for Medicare & Medicaid Services (CMS). We performed an interrupted time series analyses to evaluate trends in utilization of osteoporosis drugs before and …


Efficacy Of Electromyography And The Dead Bug Exercise, Taylor M. Scavo, Rachel C. Cooklin, Erika N. Faria, Madeline L. Johnson, Eric Sternlicht May 2017

Efficacy Of Electromyography And The Dead Bug Exercise, Taylor M. Scavo, Rachel C. Cooklin, Erika N. Faria, Madeline L. Johnson, Eric Sternlicht

Student Scholar Symposium Abstracts and Posters

The Dead Bug exercise is performed in physical therapy clinics to restore lumbar spine stability and core strength in patients with lower back pain (LBP). The aim of this study was to evaluate the efficacy of using electromyography (EMG) feedback to enhance proper mechanics during the Dead Bug exercise. Sixteen healthy, college age students volunteered as subjects for the study. Subjects performed the Dead Bug (Fig. 1a.) with and without visual EMG cues and were given instructions on how to execute the exercise. Data was recorded using a BTS FREEEMG Analyzer and signal processed and data analyzed using the BTS …


Osteoblast-Derived Fgf9 Regulates Skeletal Homeostasis, Liping Wang, Theresa M. Roth, Marcia J. Abbott, Linh Ho, Lalita Wattanachanya, Robert A. Nissenson Feb 2017

Osteoblast-Derived Fgf9 Regulates Skeletal Homeostasis, Liping Wang, Theresa M. Roth, Marcia J. Abbott, Linh Ho, Lalita Wattanachanya, Robert A. Nissenson

Health Sciences and Kinesiology Faculty Articles

FGF9 has complex and important roles in skeletal development and repair. We have previously observed that Fgf9 expression in osteoblasts (OBs) is regulated by G protein signaling and therefore the present study was done to determine whether OB-derived FGF9 was important in skeletal homeostasis. To directly test this idea, we deleted functional expression of Fgf9 gene in OBs using a 2.3 kb collagen type I promoter-driven Cre transgenic mouse line (Fgf9OB −/−). Both Fgf9 knockout (Fgf9OB −/−) and the Fgf9 floxed littermates (Fgf9fl/fl) mice were fully backcrossed and maintained in an FBV/N background. Three …


Il-15 Mediates Mitochondrial Activity Through A Ppar𝛿-Dependent-Ppar𝛼-Independent Mechanism In Skeletal Muscle Cells, Shantaé M. Thornton, James E. Krolopp, Marcia J. Abbott Jan 2016

Il-15 Mediates Mitochondrial Activity Through A Ppar𝛿-Dependent-Ppar𝛼-Independent Mechanism In Skeletal Muscle Cells, Shantaé M. Thornton, James E. Krolopp, Marcia J. Abbott

Health Sciences and Kinesiology Faculty Articles

Molecular mediators of metabolic processes, to increase energy expenditure, have become a focus for therapies of obesity. The discovery of cytokines secreted from the skeletal muscle (SKM), termed “myokines,” has garnered attention due to their positive effects on metabolic processes. Interleukin-15 (IL-15) is a myokine that has numerous positive metabolic effects and is linked to the PPAR family of mitochondrial regulators. Here, we aimed to determine the importance of PPAR𝛼 and/or PPAR𝛿 as targets of IL-15 signaling. C2C12 SKM cells were differentiated for 6 days and treated every other day with IL-15 (100 ng/mL), a PPAR𝛼 inhibitor (GW-6471), a PPAR𝛿 …


Characterization Of Inhibitor Of Differentiation (Id) Proteins In Human Cornea, Rajiv R. Mohan, Brandie R. Morgan, Govinduraj Anumanthan, Ajay Sharma, Shyam S. Chaurasia, Frank G. Rieger Jan 2016

Characterization Of Inhibitor Of Differentiation (Id) Proteins In Human Cornea, Rajiv R. Mohan, Brandie R. Morgan, Govinduraj Anumanthan, Ajay Sharma, Shyam S. Chaurasia, Frank G. Rieger

Pharmacy Faculty Articles and Research

Inhibitor of differentiation (Id) proteins are DNA-binding transcription factors involved in cellular proliferation, migration, inflammation, angiogenesis and fibrosis. However, their expression and role in the cornea is unknown. The present study was undertaken to characterize the expression of Id proteins and their interactions with the pro-fibrotic cytokine Transforming Growth Factor β1 (TGFβ1) and anti-fibrotic cytokine, bone morphogenic protein 7 (BMP7) in human cornea. Human donor corneas procured from Eye Bank were used. Id proteins were localized in human corneal sections using immunofluorescence. Primary cultures of human corneal fibroblasts (HCF) were established and treated with either TGFβ1 (5 ng/ml) or BMP7 …


Molecular Mechanisms Of Suberoylanilide Hydroxamic Acid In The Inhibition Of Tgf-Β1-Mediated Canine Corneal Fibrosis, Kristina M. Gronkiewicz, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan Jan 2016

Molecular Mechanisms Of Suberoylanilide Hydroxamic Acid In The Inhibition Of Tgf-Β1-Mediated Canine Corneal Fibrosis, Kristina M. Gronkiewicz, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To investigate molecular mechanisms mediating anti-fibrotic effect of SAHA in the canine cornea using an in vitro model. We hypothesized that SAHA attenuates corneal fibrosis by modulating Smad-dependent and, to a lesser extent, Smad-independent signaling pathways activated by TGF-β1, as well as matrix metalloproteinase (MMP) activity.

Methods—Cultured canine corneal fibroblasts (CCF) were incubated in the presence/absence of TGF-β1 (5ng/ml) and SAHA (2.5μM) for 24hrs. Western blot analysis was used to quantify non-phosphorylated and phosphorylated isoforms of Smad2/3, p38 MAP kinase (MAPK), ERK1/2 and JNK1. Real-time PCR and zymography were utilized to quantify MMP1, MMP2, MMP8 and MMP9 mRNA expression and …


Epigenetic Modification Prevents Excessive Wound Healing And Scar Formation After Glaucoma Filtration Surgery, Ajay Sharma, Govindaraj Anumanthan, Marcos Reyes, Huiyi Chen, Jason W. Brubaker, Saad Siddiqui, Suneel Gupta, Frank G. Rieger, Rajiv R. Mohan Jan 2016

Epigenetic Modification Prevents Excessive Wound Healing And Scar Formation After Glaucoma Filtration Surgery, Ajay Sharma, Govindaraj Anumanthan, Marcos Reyes, Huiyi Chen, Jason W. Brubaker, Saad Siddiqui, Suneel Gupta, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. The purpose of this study was to determine the efficacy of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACi), in prevention of excessive wound healing and scar formation in a rabbit model of glaucoma filtration surgery (GFS).

METHODS. A rabbit model of GFS was used. Rabbits that underwent GFS received balanced salt solution, or SAHA (50 lM), or mitomycin C (0.02%). Clinical scores of IOP, bleb vascularity, and slit-lamp examination were performed. On postoperative day 14, rabbits were killed and the bleb tissues were collected for evaluation of tissue fibrosis with hematoxylin and eosin, Masson trichrome, a-smooth muscle …


Development Of A Novel In Vivo Corneal Fibrosis Model In The Dog, K. M. Gronkiewicz, Elizabeth A. Giuliano, K. Kuroki, F. Bunyak, Ajay Sharma, L. B. C. Teixeira, C. W. Hamm, R. R. Mohan Jan 2016

Development Of A Novel In Vivo Corneal Fibrosis Model In The Dog, K. M. Gronkiewicz, Elizabeth A. Giuliano, K. Kuroki, F. Bunyak, Ajay Sharma, L. B. C. Teixeira, C. W. Hamm, R. R. Mohan

Pharmacy Faculty Articles and Research

The aim of this study was to develop a novel in vivo corneal model of fibrosis in dogs utilizing alkali burn and determine the ability of suberanilohydroxamic acid (SAHA) to inhibit corneal fibrosis using this large animal model. To accomplish this, we used seven research Beagle dogs. An axial corneal alkali burn in dogs was created using 1 N NaOH topically. Six dogs were randomly and equally assigned into 2 groups: A) vehicle (DMSO, 2 μL/mL); B) anti-fibrotic treatment (50 μM SAHA). The degree of corneal opacity, ocular health, and anti-fibrotic effects of SAHA were determined utilizing the Fantes grading …


Influence Of Pelvis Impact Angle During A Fall: On The Protective Benefit Of Hip Protectors, Woochol J. Choi, Stephen N. Robinovitch Aug 2015

Influence Of Pelvis Impact Angle During A Fall: On The Protective Benefit Of Hip Protectors, Woochol J. Choi, Stephen N. Robinovitch

Physical Therapy Faculty Articles and Research

"Over 90% of hip fractures are due to falls [1]. Laboratory measures have shown that wearable hip protectors reduce impact forces to the proximal femur during a simulated sideways fall on the hip [2, 3]. However, clinical evidence suggests that hip fractures still occur when hip protectors are worn [4]. Furthermore, while falls in real life result in a variety of impact configurations, biomechanical tests to date have focused only on lateral impact to the pelvis. In the current study, we examined how the force reduction provided by wearable hip protectors is affected by pelvis impact configuration during simulated sideways …


Effects Of Pelvis Impact Angle And Hip Muscle Forces On Hip Fracture Risk During A Fall Using An Advanced Hip Impact Simulator, Woochol J. Choi, Stephen N. Robinovitch Aug 2015

Effects Of Pelvis Impact Angle And Hip Muscle Forces On Hip Fracture Risk During A Fall Using An Advanced Hip Impact Simulator, Woochol J. Choi, Stephen N. Robinovitch

Physical Therapy Faculty Articles and Research

"Over 90% of hip fractures in older adults are caused by falls [1]. Whether a given fall will cause hip fracture depends on bone strength, and on the impact force and stress applied to the bone during impact [2]. Improved understanding is required on how peak bone stresses during a fall depend on the mechanics of a fall, and on the state of contraction at the moment of impact of the muscles spanning the hip. Recently, Choi et al showed that, for lateral impact to the hip, peak stresses decrease with increases in hip abductor muscle force [3]. In the …


Neural Function, Injury, And Stroke Subtype Predict Treatment Gains After Stroke, Erin Burke Quinlan, Lucy Dodakian, Jill See, Alison Mackenzie, Vu Le, Mike Wojnowicz, Babak Shahbaba, Steven C. Cramer Jan 2015

Neural Function, Injury, And Stroke Subtype Predict Treatment Gains After Stroke, Erin Burke Quinlan, Lucy Dodakian, Jill See, Alison Mackenzie, Vu Le, Mike Wojnowicz, Babak Shahbaba, Steven C. Cramer

Physical Therapy Faculty Articles and Research

Objective

This study was undertaken to better understand the high variability in response seen when treating human subjects with restorative therapies poststroke. Preclinical studies suggest that neural function, neural injury, and clinical status each influence treatment gains; therefore, the current study hypothesized that a multivariate approach incorporating these 3 measures would have the greatest predictive value.

Methods

Patients 3 to 6 months poststroke underwent a battery of assessments before receiving 3 weeks of standardized upper extremity robotic therapy. Candidate predictors included measures of brain injury (including to gray and white matter), neural function (cortical function and cortical connectivity), and clinical …


Role Of 5'Tg3'-Interacting Factors (Tgifs) In Vorinostat (Hdac Inhibitor)-Mediated Corneal Fibrosis Inhibition, Ajay Sharma, Nishant R. Sinha, Saad Siddiqui, Rajiv R. Mohan Jan 2015

Role Of 5'Tg3'-Interacting Factors (Tgifs) In Vorinostat (Hdac Inhibitor)-Mediated Corneal Fibrosis Inhibition, Ajay Sharma, Nishant R. Sinha, Saad Siddiqui, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: We have previously reported that vorinostat, an FDA-approved, clinically used histone deacetylase (HDAC) inhibitor, attenuates corneal fibrosis in vivo in rabbits by blocking transforming growth factor β (TGFβ). The 5′TG3′-interacting factors (TGIFs) are transcriptional repressors of TGFβ1 signaling via the Smad pathway. The present study was designed to explore the expression of TGIFs in human corneal fibroblasts and to investigate their role in mediating the antifibrotic effect of vorinostat.

Methods: Human corneal fibroblast cultures were generated from donor corneas. RNA isolation, cDNA preparation, and PCR were performed to detect the presence of TGIF1 and TGIF2 transcripts. The cultures were …


The Effect Of Chronic Sleep Deprivation On Tumor Necrosis Factor Alpha And Bone Health In Peri-Menopausal Rats, Megan Robertson, Derek Booth, Erin Wainwright, Cody Arbuckle, Frank Frisch Dec 2014

The Effect Of Chronic Sleep Deprivation On Tumor Necrosis Factor Alpha And Bone Health In Peri-Menopausal Rats, Megan Robertson, Derek Booth, Erin Wainwright, Cody Arbuckle, Frank Frisch

Student Scholar Symposium Abstracts and Posters

Post-menopausal osteoporosis is a common syndrome in the United States. The cessation of estrogen signaling coupled with the production of pro-inflammatory cytokines from sleep deprivation leads to an even greater risk of post-menopausal osteoporosis by creating an imbalance between osteoblasts and osteoclasts. With estrogen no longer present to regulate the concentration of osteoclasts and pro-inflammatory cytokines increasing production of osteoclasts, bone is degraded at a faster rate than it is formed. One of the most common treatments for osteoporosis is Zolendronate (a nitrogenous bisphosphonate), which decreases the number of osteoclasts in bone. This preliminary study looked at the effects on …


Corneal Gene Therapy: Basic Science And Translational Perspective, Rajiv R. Mohan, Jason T. Rodier, Ajay Sharma Jan 2013

Corneal Gene Therapy: Basic Science And Translational Perspective, Rajiv R. Mohan, Jason T. Rodier, Ajay Sharma

Pharmacy Faculty Articles and Research

Corneal blindness is the third leading cause of blindness worldwide. Gene therapy is an emerging technology for corneal blindness due to the accessibility and immune-privileged nature of the cornea, ease of vector administration and visual monitoring, and ability to perform frequent noninvasive corneal assessment. Vision restoration by gene therapy is contingent upon vector and mode of therapeutic gene introduction into targeted cells/tissues. Numerous efficacious vectors, delivery techniques, and approaches have evolved in last decade for developing gene-based interventions for corneal diseases. Maximizing the potential benefits of gene therapy requires efficient and sustained therapeutic gene expression in target cells, low toxicity, …


Bmp7 Gene Transfer Via Gold Nanoparticles Into Stroma Inhibits Corneal Fibrosis In Vivo, Ashish Tandon, Ajay Sharma, Jason T. Rodier, Alexander M. Klibanov, Frank G. Rieger, Rajiv R. Mohan Jan 2013

Bmp7 Gene Transfer Via Gold Nanoparticles Into Stroma Inhibits Corneal Fibrosis In Vivo, Ashish Tandon, Ajay Sharma, Jason T. Rodier, Alexander M. Klibanov, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

This study examined the effects of BMP7 gene transfer on corneal wound healing and fibrosis inhibition in vivo using a rabbit model. Corneal haze in rabbits was produced with the excimer laser performing -9 diopters photorefractive keratectomy. BMP7 gene was introduced into rabbit keratocytes by polyethylimine-conjugated gold nanoparticles (PEI2- GNPs) transfection solution single 5-minute topical application on the eye. Corneal haze and ocular health in live animals was gauged with stereo- and slit-lamp biomicroscopy. The levels of fibrosis [a-smooth muscle actin (aSMA), F-actin and fibronectin], immune reaction (CD11b and F4/80), keratocyte apoptosis (TUNEL), calcification (alizarin red, vonKossa and osteocalcin), and …


Vorinostat: A Potent Agent To Prevent And Treat Laser-Induced Corneal Haze, Ashish Tandon, Jonathan C. K. Tovey, Michael R. Waggoner, Ajay Sharma, John W. Cowden, Daniel J. Gibson, Yuanjing Liu, Gregory S. Schultz, Rajiv R. Mohan Jan 2012

Vorinostat: A Potent Agent To Prevent And Treat Laser-Induced Corneal Haze, Ashish Tandon, Jonathan C. K. Tovey, Michael R. Waggoner, Ajay Sharma, John W. Cowden, Daniel J. Gibson, Yuanjing Liu, Gregory S. Schultz, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE—This study investigated the efficacy and safety of vorinostat, a deacetylase (HDAC) inhibitor, in the treatment of laser-induced corneal haze following photorefractive keratectomy (PRK) in rabbits in vivo and transforming growth factor beta 1 (TGFβ1) -induced corneal fibrosis in vitro.

METHODS—Corneal haze in rabbits was produced with −9.00 diopters (D) PRK. Fibrosis in cultured human and rabbit corneal fibroblasts was activated with TGFβ1. Vorinostat (25 μm) was topically applied once for 5 minutes on rabbit cornea immediately after PRK for in vivo studies. Vorinostat (0 to 25 μm) was given to human/rabbit corneal fibroblasts for 5 minutes or 48 …


Attenuation Of Corneal Myofibroblast Development Through Nanoparticle-Mediated Soluble Transforming Growth Factor-Β Type Ii Receptor (Stgfβrii) Gene Transfer, Ajay Sharma, Jason T. Rodier, Ashish Tandon, Alexander M. Klibanov, Rajiv R. Mohan Jan 2012

Attenuation Of Corneal Myofibroblast Development Through Nanoparticle-Mediated Soluble Transforming Growth Factor-Β Type Ii Receptor (Stgfβrii) Gene Transfer, Ajay Sharma, Jason T. Rodier, Ashish Tandon, Alexander M. Klibanov, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: To explore (i) the potential of polyethylenimine (PEI)-DNA nanoparticles as a vector for delivering genes into human corneal fibroblasts, and (ii) whether the nanoparticle-mediated soluble extracellular domain of the transforming growth factor–β type II receptor (sTGFβRII) gene therapy could be used to reduce myofibroblasts and fibrosis in the cornea using an in vitro model.

Methods: PEI-DNA nanoparticles were prepared at a nitrogen-to-phosphate ratio of 30 by mixing linear PEI and a plasmid encoding sTGFβRII conjugated to the fragment crystallizable (Fc) portion of human immunoglobulin. The PEI-DNA polyplex formation was confirmed through gel retardation assay. Human corneal fibroblasts (HCFs) were …


Gene Therapy In The Cornea: 2005--Present, Rajiv R. Mohan, Jonathan C. K. Tovey, Ajay Sharma, Ashish Tandon Jan 2012

Gene Therapy In The Cornea: 2005--Present, Rajiv R. Mohan, Jonathan C. K. Tovey, Ajay Sharma, Ashish Tandon

Pharmacy Faculty Articles and Research

Successful restoration of vision in human patients with gene therapy affirmed its promise to cure ocular diseases and disorders. The efficacy of gene therapy is contingent upon vector and mode of therapeutic DNA introduction into targeted cells/tissues. The cornea is an ideal tissue for gene therapy due to its ease of access and relative immune-privilege. Considerable progress has been made in the field of corneal gene therapy in last 5 years. Several new gene transfer vectors, techniques and approaches have evolved. Although corneal gene therapy is still in its early stages of development, the potential of gene-based interventions to treat …


Pressure Distribution Over The Palm Region During Forward Falls On The Outstretched Hands, Woochol J. Choi, Stephen N. Robinovitch Feb 2011

Pressure Distribution Over The Palm Region During Forward Falls On The Outstretched Hands, Woochol J. Choi, Stephen N. Robinovitch

Physical Therapy Faculty Articles and Research

Falls on the outstretched hands are the cause of over 90% of wrist fractures, yet little is known about bone loading during this event. We tested how the magnitude and distribution of pressure over the palm region during a forward fall is affected by foam padding (simulating a glove) and arm configuration, and by the faller’s body mass index (BMI) and thickness of soft tissues over the palm region.

Thirteen young women with high (n=7) or low (n=6) BMI participated in a “torso release experiment” that simulated falling on both outstretched hands with the arm inclined either at 20° or …


Significant Inhibition Of Corneal Scarring In Vivo With Tissue-Selective, Targeted Aav5 Decorin Gene Therapy, Rajiv R. Mohan, Ashish Tandon, Ajay Sharma, John W. Cowden, Jonathan C. K. Tovey Jan 2011

Significant Inhibition Of Corneal Scarring In Vivo With Tissue-Selective, Targeted Aav5 Decorin Gene Therapy, Rajiv R. Mohan, Ashish Tandon, Ajay Sharma, John W. Cowden, Jonathan C. K. Tovey

Pharmacy Faculty Articles and Research

PURPOSE. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the stroma with adeno-associated virus serotype 5 (AAV5) inhibits corneal fibrosis in vivo without significant side effects.

METHODS. An in vivo rabbit model of corneal fibrosis was used. Targeted decorin gene therapy was delivered to the rabbit cornea by a single topical application of AAV5 (100 L; 6.5 1012 g/mL) onto the bare stroma for 2 minutes. The levels of corneal fibrosis were determined with stereomicroscopy, slit lamp biomicroscopy, -smooth muscle actin ( SMA), fibronectin, and F-actin immunocytochemistry, and/or immunoblotting. CD11b, F4/80 immunocytochemistry, and TUNEL assay …


Targeted Decorin Gene Therapy Delivered With Adeno-Associated Virus Effectively Retards Corneal Neovascularization In Vivo, Rajiv R. Mohan, Jonathan C. K. Tovey, Ajay Sharma, Gregory S. Schultz, John W. Cowden, Ashish Tandon Jan 2011

Targeted Decorin Gene Therapy Delivered With Adeno-Associated Virus Effectively Retards Corneal Neovascularization In Vivo, Rajiv R. Mohan, Jonathan C. K. Tovey, Ajay Sharma, Gregory S. Schultz, John W. Cowden, Ashish Tandon

Pharmacy Faculty Articles and Research

Decorin, small leucine-rich proteoglycan, has been shown to modulate angiogenesis in nonocular tissues. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the rabbit stroma with adeno-associated virus serotype 5 (AAV5) impedes corneal neovascularization (CNV) in vivo without significant side effects. An established rabbit CNV model was used. Targeted decorin gene therapy in the rabbit stroma was delivered with a single topical AAV5 titer (100 μl; 5x10^12 vg/ml) application onto the stroma for two minutes after removing corneal epithelium. The levels of CNV were examined with stereomicroscopy, H&E staining, lectin, collagen type IV, CD31 immunocytochemistry and …


Polyethylenimine-Conjugated Gold Nanoparticles: Gene Transfer Potential And Low Toxicity In The Cornea, Ajay Sharma, Ashish Tandon, Jonathan C. K. Tovey, Rangan Gupta, J. David Robertson, Jennifer A. Fortune, Alexander M. Klibanov, John W. Cowden, Frank G. Rieger, Rajiv R. Mohan Jan 2011

Polyethylenimine-Conjugated Gold Nanoparticles: Gene Transfer Potential And Low Toxicity In The Cornea, Ajay Sharma, Ashish Tandon, Jonathan C. K. Tovey, Rangan Gupta, J. David Robertson, Jennifer A. Fortune, Alexander M. Klibanov, John W. Cowden, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

This study examined the gene transfer efficiency and toxicity of 2-kDa polyethylenimine conjugated to gold nanoparticles (PEI2-GNP) in the human cornea in vitro and rabbit cornea in vivo. PEI2-GNP with nitrogen-to-phosphorus (N/P) ratios of up to 180 exhibited significant transgene delivery in the human cornea without altering the viability or phenotype of these cells. Similarly, PEI2-GNP applied to corneal tissues collected after 12 h, 72 h, or 7 days exhibited appreciable gold uptake throughout the rabbit stroma with gradual clearance of GNP over time. Transmission electron microscopy detected GNP in the keratocytes and the extracellular matrix of the rabbit corneas. …


Efficacious And Safe Tissue-Selective Controlled Gene Therapy Approaches For The Cornea, Rajiv R. Mohan, Sunilima Sinha, Ashish Tandon, Rangan Gupta, Jonathan C. K. Tovey, Ajay Sharma Jan 2011

Efficacious And Safe Tissue-Selective Controlled Gene Therapy Approaches For The Cornea, Rajiv R. Mohan, Sunilima Sinha, Ashish Tandon, Rangan Gupta, Jonathan C. K. Tovey, Ajay Sharma

Pharmacy Faculty Articles and Research

Untargeted and uncontrolled gene delivery is a major cause of gene therapy failure. This study aimed to define efficient and safe tissue-selective targeted gene therapy approaches for delivering genes into keratocytes of the cornea in vivo using a normal or diseased rabbit model. New Zealand White rabbits, adeno-associated virus serotype 5 (AAV5), and a minimally invasive hair-dryer based vector-delivery technique were used. Fifty microliters of AAV5 titer (6.561012 vg/ml) expressing green fluorescent protein gene (GFP) was topically applied onto normal or diseased (fibrotic or neovascularized) rabbit corneas for 2-minutes with a custom vector-delivery technique. Corneal fibrosis and neovascularization in rabbit …


Pressure Distribution Over The Palm During Falls On The Outstretched Hands, Woochol J. Choi, Stephen N. Robinovitch Mar 2010

Pressure Distribution Over The Palm During Falls On The Outstretched Hands, Woochol J. Choi, Stephen N. Robinovitch

Physical Therapy Faculty Articles and Research

"Over 90% of wrist fractures are caused by falls on the outstretched hands (Palvanen et al., Osteoporos Int, 2000). Along with bone strength, fracture risk depends on the magnitude and distribution of force to soft and hard tissues during impact. In the current study, we examined how pressure distribution over the palm during a fall is affected by impact configuration, body mass index (BMI), palmer soft tissue thickness, and a 5 mm thick foam pad (simulating a protective glove)."