Digital Commons Network^™

Gut Microbiota And Cardiovascular Uremic Toxicities, Manuel T. Velasquez, Patricia Centron, Ian Barrows, Rama Dwivedi, Dominic S. Raj

Medicine Faculty Publications

Cardiovascular disease (CVD) remains a major cause of high morbidity and mortality in patients with chronic kidney disease (CKD). Numerous CVD risk factors in CKD patients have been described, but these do not fully explain the high pervasiveness of CVD or increased mortality rates in CKD patients. In CKD the loss of urinary excretory function results in the retention of various substances referred to as “uremic retention solutes”. Many of these molecules have been found to exert toxicity on virtually all organ systems of the human body, leading to the clinical syndrome of uremia. In recent years, an increasing body …

The Neurodevelopmental Perspective Of Surgical Necrotizing Enterocolitis: The Role Of The Gut-Brain Axis., Chariton Moschopoulos, Panagiotis Kratimenos, Ioannis Koutroulis, Bhairav V Shah, Anja Mowes, Vineet Bhandari

Pediatrics Faculty Publications

This state-of-the-art review article aims to highlight the most recent evidence about the therapeutic options of surgical necrotizing enterocolitis, focusing on the molecular basis of the gut-brain axis in relevance to the neurodevelopmental outcomes of primary peritoneal drainage and primary laparotomy. Current evidence favors primary laparotomy over primary peritoneal drainage as regards neurodevelopment in the surgical treatment of necrotizing enterocolitis. The added exposure to inhalational anesthesia in infants undergoing primary laparotomy is an additional confounding variable but requires further study. The concept of the gut-brain axis suggests that bowel injury initiates systemic inflammation potentially affecting the developing central nervous system. …

Pd-L1 Checkpoint Inhibition And Anti-Ctla-4 Whole Tumor Cell Vaccination Counter Adaptive Immune Resistance: A Mouse Neuroblastoma Model That Mimics Human Disease., Priya Srinivasan, Xiaofang Wu, Mousumi Basu, Christopher Rossi, Anthony D Sandler

Pathology Faculty Publications

BACKGROUND: Adaptive immune resistance induces an immunosuppressive tumor environment that enables immune evasion. This phenomenon results in tumor escape with progression and metastasis. Programmed cell death-ligand 1 (PD-L1) expressed on tumors is thought to inhibit tumor-infiltrating lymphocytes (TILs) through programmed cell death 1 (PD1), enabling adaptive immune resistance. This study investigates the role of PD-L1 in both mouse and human neuroblastoma immunity. The consequence of PD-L1 inhibition is characterized in the context of an established whole tumor cell vaccine.

METHODS AND FINDINGS: A mouse model of neuroblastoma was investigated using an Id2 knockdown whole cell vaccine in combination with checkpoint …

Epha2/Ephrin-A1 Mediate Corneal Epithelial Cell Compartmentalization Via Adam10 Regulation Of Egfr Signaling., Nihal Kaplan, Rosa Ventrella, Han Peng, Sonali Pal-Ghosh, Constadina Arvanitis, Joshua Z Rappoport, Brian J Mitchell, Mary Ann Stepp, Robert M Lavker, Spiro Getsios

Anatomy and Regenerative Biology Faculty Publications

Purpose: Progenitor cells of the limbal epithelium reside in a discrete area peripheral to the more differentiated corneal epithelium and maintain tissue homeostasis. What regulates the limbal-corneal epithelial boundary is a major unanswered question. Ephrin-A1 ligand is enriched in the limbal epithelium, whereas EphA2 receptor is concentrated in the corneal epithelium. This reciprocal pattern led us to assess the role of ephrin-A1 and EphA2 in limbal-corneal epithelial boundary organization.

Methods: EphA2-expressing corneal epithelial cells engineered to express ephrin-A1 were used to study boundary formation in vitro in a manner that mimicked the relative abundance of these juxtamembrane signaling proteins in …

Spotlight On Once-Monthly Long-Acting Injectable Aripiprazole And Its Potential As Maintenance Treatment For Bipolar I Disorder In Adult Patients., Vanessa Torres-Llenza, Pooja Lakshmin, Daniel Z Lieberman

Psychiatry and Behavioral Sciences Faculty Publications

The lack of long-term medication adherence is a challenge in the treatment of bipolar disorder, particularly during the maintenance phase when symptoms are less prominent. The rate of nonadherence is ~20%-60% depending on how strict a definition is used. Nonadherence worsens the course of bipolar disorder and can add hundreds of thousands of dollars to the lifetime cost of treating the illness. Long-acting injectable (LAI) medication is an attractive alternative to daily dosing of oral medication, especially among patients who are ambivalent about treatment. The purpose of this paper is to review the evidence for the safety and efficacy of …

Antiretroviral Therapy Interruptions: Impact On Hiv Treatment And Transmission., Gueorgui Dubrocq, Natella Rakhmanina

Pediatrics Faculty Publications

Introduction: Successful management of pediatric and adult human immunodeficiency virus (HIV) disease includes lifelong administration of antiretroviral therapy (ART). The need for the continuous use of antiretroviral drugs throughout the life course poses a challenge to children, adolescents, and adults living with HIV and their caregivers. Historically, treatment interruptions have been viewed as a negative therapeutic strategy. Recently, however, treatment interruptions or treatment reduction strategies have become a focus of investigations as innovative approaches to the long-term management of HIV disease. Current challenges with treatment interruptions include identifying an appropriate timeframe for length of interruptions and identifying HIV patient populations …

Among Patients With Endometriosis, Does The Use Of Serum Biomarkers, Versus Laparoscopic Surgery For Diagnosis And Staging Of The Disease Decrease The Incidence Of Disease Related Negative Outcomes, Ellyn C. Hexum

Theses and Graduate Projects

Objective: To determine the ability and efficacy of non-invasive serum biomarker testing as a replacement for laparoscopic surgery in the diagnosis and staging of endometriosis to decrease the incidence of negative disease outcomes, leading to improvement in the accuracy of diagnoses and patient tailored treatment protocols.

Background: Endometriosis is a debilitating inflammatory disease of the reproductive tract. Currently, the gold standard for the diagnosis and staging of endometriosis is exploratory laparoscopic surgery. The use of surgery as the source of achieving a definitive diagnosis holds the potential to increase the incidence of negative disease outcomes. Because of this, the use …

Are Platelet Rich Plasma Injections A Better Choice Compared To Glucocorticoid Injections For The Treatment Of Rotator Cuff Tendinopathy In Adult Patients?, Sawyer Lange

Theses and Graduate Projects

An estimated 16 to 34 percent of the general population will experience shoulder pain at some point in their life. Rotator cuff tendinopathy makes up a large portion of that percentage. Platelet rich plasma (PRP) is an autologous blood product that has supraphsyiologic levels of growth factors and cytokines that have the potential to expedite the tendon healing process. This literature review will look at the current science surrounding PRP and look at studies comparing its efficacy to the commonly used corticosteroid injection.

Do Non-Steroidal Anti-Inflammatory Drugs Increase The Risk For Non- Or Mal-Union Following Acute Fracture? A Literature Review, Bryan Moritz

Theses and Graduate Projects

NSAID medications are among the most commonly used analgesic medications world wide, and it was estimated in 2010 (updated 2015 data is expected to be published next year) that about 29 million adults in the United States regularly used NSAID medications at least three times per week for more than three months. Fracture healing has been shown to be dependent on the inflammatory cascade. NSAID medication use appears to have a mechanistic in-vivo and in-vitro animal risk for the development of non- and mal-union following fracture. However, human data is lacking to support total avoidance of this analgesic option for …

Therapeutic Hypothermia For Neonatal Hypoxic Ischemic Encephalopathy: Effects On Neurodevelopmental Outcomes, Claire Rustad

Theses and Graduate Projects

Therapeutic hypothermia is a standardized protocol in the management of term- or near- term neonates who have suffered asphyxia in the perinatal period. Birth asphyxia, if sustained, may develop into a more serious condition known as hypoxic ischemic encephalopathy (HIE). Depending on severity, HIE is associated with adverse cognitive and neurodevelopmental outcomes, yet through various physiological mechanisms, hypothermia sustained for a 72-hour period has been shown to attenuate, or even prevent, permanent brain damage by decreasing cerebral energy demands. Unfortunately, cognitive and neurodevelopmental outcomes are difficult to prognosticate before or after completion of hypothermia protocol, but existing standards and technology …

Acute Post-Operative Pain Management: Preventing Overuse Of Opioids, Alison Hirsch

Theses and Graduate Projects

Background: Surgical pain management with opioids is common. The use of multimodal analgesia has been proposed in order to provide opioid-sparing regimens and improve pain control post-operatively. Inadequate control of surgical pain can lead to development of chronic pain. Furthermore, studies have linked acute surgical opioid use to increased risk of long-term use. Long-term opioid use has undesirable, life-altering consequences, including physical dependence and addiction which may lead to overdose or death. Use of a variety of medications in the operative setting can lead to synergistic or additive effects on pain control, thus decreasing post-operative opioid consumption.

Methods: A literature …

The Future Of 5-Fluorouracil Treatment Of Colorectal Cancer: Translating A Better Understanding Into Improved Patient Care, Nathan Smits

Theses and Graduate Projects

5-fluorouracil (5-FU) is a pyrimidine analog that has been successfully employed in anticancer therapy for over forty years. Over the past several decades, researchers have characterized its cellular and clinical pharmacology and uncovered multiple mechanisms of action, which include the inhibition of thymidylate synthase (TS) and incorporation of its metabolites into DNA and RNA. The purpose of this quantitative systemic review was to summarize and evaluate what is known of these mechanisms to determine which are of most significance in the anticancer effects of 5-FU in metastatic colorectal cancer (mCRC) patients. A literature search of peer-reviewed articles dating back to …

Effect Of Low-Intensity Long-Duration Ultrasound On The Symptomatic Relief Of Knee Osteoarthritis: A Randomized, Placebo-Controlled Double-Blind Study, Dominic Klyve, Ralph Ortiz, Davie O. Draper, Thomas M. Best

Mathematics Faculty Scholarship

Background: Wearable long-duration low-intensity ultrasound is an emerging non-invasive and non-narcotic therapy for the daily treatment of musculoskeletal pain. The aim of this randomized, double-blind, placebo-controlled study was to examine whether long-duration low-intensity ultrasound was effective in treating pain and improving function in patients with knee osteoarthritis. Methods: Ninety patients with moderate to severe knee pain and radiographically confirmed knee osteoarthritis (Kellgren-Lawrence grade I/II) were randomized for treatment with active (n = 55) or placebo (n = 35) devices applied daily to the treated knee. Investigators and subjects were blinded to treatment groups. Ultrasound (3 MHz, 0.132 W/cm2, 1.3 W) …

Aminoglycosides Rapidly Inhibit Nad(P)H Metabolism Increasing Reactive Oxygen Species And Cochlear Cell Demise, Danielle E. Desa, Michael G. Nichols, Heather Jensen Smith

Journal Articles: Eppley Institute

Despite causing permanent hearing loss by damaging inner ear sensory cells, aminoglycosides (AGs) remain one of the most widely used classes of antibiotics in the world. Although the mechanisms of cochlear sensory cell damage are not fully known, reactive oxygen species (ROS) are clearly implicated. Mitochondrial-specific ROS formation was evaluated in acutely cultured murine cochlear explants exposed to gentamicin (GM), a representative ototoxic AG antibiotic. Superoxide (O2·-) and hydrogen peroxide (H2O2) were measured using MitoSOX Red and Dihydrorhodamine 123, respectively, in sensory and supporting cells. A 1-h GM exposure significantly increased O2·- formation in IHCs and increased H2O2 formation in …

Inter-Vendor Reproducibility Of Left And Right Ventricular Cardiovascular Magnetic Resonance Myocardial Feature-Tracking, Roman Johannes Gertz, Torben Lange, Johannes Tammo Kowallick, Sören Jan Backhaus, Michael Steinmetz, Wieland Staab, Shelby Kutty, Gerd Hasenfuß, Joachim Lotz, Andreas Schuster

Journal Articles: Cardiology

AIM: Since cardiovascular magnetic resonance feature-tracking (CMR-FT) has been demonstrated to be of incremental clinical merit we investigated the interchangeability of global left and right ventricular strain parameters between different CMR-FT software solutions.

MATERIAL AND METHODS: CMR-cine images of 10 patients without significant reduction in LVEF and RVEF and 10 patients with a significantly impaired systolic function were analyzed using two different types of FT-software (TomTec, Germany; QStrain, Netherlands). Global longitudinal strains (LV GLS, RV GLS), global left ventricular circumferential (GCS) and radial strains (GRS) were assessed. Differences in intra- and inter-observer variability within and between software types based on …

The Effects Of A Cognitive Training Program For Cognitively Intact Older Adults, Caroline Kinskey

All Graduate Theses, Dissertations, and Other Capstone Projects

Cognitive training is a term used to describe programs that provide guided practice on tasks requiring different cognitive abilities such as memory or language. It is assumed that regular practice will improve or maintain functioning in a particular cognitive domain (e.g., memory) and those results will generalize beyond the context of training. Results have been mixed in the existing literature that has evaluated the potential benefits of cognitive training on cognitive and emotional functioning in cognitively intact older adults. This study investigated the effectiveness of a cognitive training program for older adults with no to very minimal cognitive decline. Nine …

The Effects Of Hormone Replacement Therapy (Hrt) On Surgically Postmenopausal Women: A Review Of The Literature, Leslie M. Hertweck

Honors Undergraduate Theses

The primary purpose of this research was to examine the effects of HRT in women with acute estrogen deficiency from surgically induced menopause. The secondary purpose was to evaluate how HRT improves symptoms of acute estrogen deficiency and quality of life (QOL) in women using hormone supplementation. Peer reviewed articles published from 2000 to 2017 that were written in the English language with a focus on the use of HRT in women with acute estrogen deficiency after surgical menopause were evaluated for relevance. Evidence suggests the primary reason for decreased use of HRT is the associated risks outweighing the benefits; …

Peptide Density Targets And Impedes Triple Negative Breast Cancer Metastasis, Daxing Liu, Peng Guo, Craig Mccarthy, Biran Wang, Yu Tao, Debra Auguste

Publications and Research

The C-X-C chemokine receptor type 4 (CXCR4, CD184) pathway is a key regulator of cancer metastasis. Existing therapeutics that block CXCR4 signaling are dependent on single molecule-receptor interactions or silencing CXCR4 expression. CXCR4 localizes in lipid rafts and forms dimers therefore CXCR4 targeting and signaling may depend on ligand density. Herein, we report liposomes presenting a CXCR4 binding peptide (DV1) as a threedimensional molecular array, ranging from 9k to 74k molecules μm−2, target triple negative breast cancer (TNBC). TNBC cells exhibit a maxima in binding and uptake of DV1functionalized liposomes (L-DV1) in vitro at a specific density, which yields a …

Continuous Monitoring Devices And Seizure Patterns By Glucose, Time And Lateralized Seizure Onset., Katie M Kinnear, Nicole M Warner, Alan M Haltiner, Michael J Doherty

Articles, Abstracts, and Reports

Objectives: To investigate if glucose levels influence seizure patterns.

Materials and methods: In a patient with RNS/NeuroPace implanted bi-temporally and type 1 diabetes mellitus, seizure event times and onset locations were matched to continuous tissue glucose.

Results: Left focal seizure (LFS, n = 22) glucoses averaged 169 mg/dL, while right focal seizure (RFS, n = 23) glucoses averaged 131 mg/dL (p = 0.03). LFS occurred at mean time 17:02 while RFS occurred at 04:23. LFS spread to the contralateral side (n = 19) more than RFS (n = 2).

Conclusion: Seizure onset laterality and spread vary with glucose and time …

Sivcpz Closely Related To The Ancestral Hiv-1 Is Less Or Non-Pathogenic To Humans In A Hu-Blt Mouse Model, Zhe Yuan, Guobin Kang, Lance Daharsh, Wenjin Fan, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

The HIV-1 pandemic is a consequence of the cross-species transmission of simian immunodeficiency virus in wild chimpanzees (SIVcpz) to humans. Our previous study demonstrated SIVcpz strains that are closely related to the ancestral viruses of HIV-1 groups M (SIVcpzMB897) and N (SIVcpzEK505) and two SIVcpz lineages that are not associated with any known HIV-1 infections in humans (SIVcpzMT145 and SIVcpzBF1167), all can readily infect and robustly replicate in the humanized-BLT mouse model of humans. However, the comparative pathogenicity of different SIVcpz strains remains unknown. Herein, we compared the pathogenicity of the above four SIVcpz strains with HIV-1 using humanized-BLT mice. …

Identification Of Unequally Represented Founder Viruses Among Tissues In Very Early Siv Rectal Transmission, Jian Chen, Yanqin Ren, Lance Daharsh, Lu Liu, Guobin Kang, Qingsheng Li, Qiang Wei, Yanmin Wu, Jianqing Xu

Nebraska Center for Virology: Faculty Publications

Characterizing the transmitted/founder (T/F) viruses of multi-variant SIV infection may shed new light on the understanding of mucosal transmission.We intrarectally inoculated six Chinese rhesus macaques with a single high dose of SIVmac251 (3.1 × 10⁴ TCID₅₀) and obtained 985 full-length env sequences from multiple tissues at 6 and 10 days post-infection by single genome amplification (SGA). All 6 monkeys were infected with a range of 2 to 8 T/F viruses and the dominant variants from the inoculum were still dominant in different tissues from each monkey. Interestingly, our data showed that a cluster of rare T/F viruses …

Discovery Of A Non-Nucleoside Rna Polymerase Inhibitor For Blocking Zika Virus Replication Through In Silico Screening, Aryamav Pattnaik, Nicholas Palermo, Bikash R. Sahoo, Zhe Yuan, Duoyi Hu, Arun S. Annamalai, Hiep L. X. Vu, Ignacio Correas, Pavan Kumar Prathipati, Christopher J. Destache, Qingsheng Li, Fernando A. Osorio, Asit K. Pattnaik, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV), an emerging arbovirus, has become a major human health concern globally due to its association with congenital abnormalities and neurological diseases. Licensed vaccines or antivirals against ZIKV are currently unavailable. Here, by employing a structure-based approach targeting the ZIKV RNA-dependent RNA polymerase (RdRp), we conducted in silico screening of a library of 100,000 small molecules and tested the top ten lead compounds for their ability to inhibit the virus replication in cell-based in vitro assays. One compound, 3-chloro-N-[({4-[4-(2-thienylcarbonyl)-1-piperazinyl]phenyl}amino)carbonothioyl]-1-benzothiophene-2-carboxamide (TPB), potently inhibited ZIKV replication at submicromolar concentrations. Molecular docking analysis suggests that …

Primary Liver Cancers, Part 2: Progression Pathways And Carcinogenesis, Kun Jiang, Barbara A. Centeno

Pathology and Cell Biology Faculty Publications

Hepatocellular carcinoma (HCC) and primary intrahepatic cholangiocarcinoma (ICC) have been increasing in incidence worldwide and are leading causes of cancer death. Studies of the molecular alterations leading to these carcinomas provide insights into the key mechanisms involved. A literature review was conducted to identify articles with information relevant to current understanding of the etiologies and molecular pathogenesis of HCC and ICC. Chronic inflammatory diseases are the key etiological risk factors for both HCC and ICC, although other diseases play a role, and for many ICCs, an underlying risk factor is not identified. Mutations in catenin beta 1 (CTNBB1) …

Plasma Derived From Human Umbilical Cord Blood: Potential Cell-Additive Or Cell-Substitute Therapeutic For Neurodegenerative Diseases, Jared Ehrhart, Paul R. Sanberg, Svitlana Garbuzova-Davis

Neurosurgery and Brain Repair Faculty Publications

Limited efficacy of current therapeutic approaches for neurodegenerative disease has led to increased interest in alternative therapies. Cord blood plasma (CBP) derived from human umbilical cord blood (hUCB) may be a potential therapeutic. Benefits of CBP injection into rodent models of aging or ischaemic stroke have been demonstrated, though how benefits are elicited is still unclear. The present study evaluated various factors within the same samples of CBP and human adult blood plasma/sera (ABP/S). Also, autologous CBP effects vs. ABP/S or foetal bovine serum supplements on mononuclear cells from hUCB (MNC hUCB) in vitro were determined. Results showed significantly low …

Reduction Of Microhemorrhages In The Spinal Cord Of Symptomatic Als Mice After Intravenous Human Bone Marrow Stem Cell Transplantation Accompanies Repair Of The Blood-Spinal Cord Barrier, David J. Eve, George Steiner, Ajay Mahendrasah, Paul R. Sanberg, Crupa Kurien, Avery Thomson, Cesar V. Borlongan, Svitlana Garbuzova-Davis

Neurosurgery and Brain Repair Faculty Publications

Blood-spinal cord barrier (BSCB) alterations, including capillary rupture, have been demonstrated in animal models of amyotrophic lateral sclerosis (ALS) and ALS patients. To date, treatment to restore BSCB in ALS is underexplored. Here, we evaluated whether intravenous transplantation of human bone marrow CD34⁺ (hBM34⁺) cells into symptomatic ALS mice leads to restoration of capillary integrity in the spinal cord as determined by detection of microhemorrhages. Three different doses of hBM34⁺ cells (5 × 10⁴, 5 × 10⁵ or 1 × 10⁶) or media were intravenously injected into symptomatic G93A SOD1 mice …

Human Umbilical Cord Blood Serum–Derived Α-Secretase: Functional Testing In Alzheimer’S Disease Mouse Models, Ahsan Habib, Huayan Hou, Takashi Mori, Jun Tian, Jin Zeng, Shengnuo Fan, Brian Giunta, Paul R. Sanberg, Darrell Sawmiller, Jun Tan

Neurosurgery and Brain Repair Faculty Publications

Alzheimer’s disease (AD) is an age-related disorder that affects cognition. Our previous studies showed that the neuroprotective fragment of amyloid procurer protein (APP) metabolite, soluble APPα (sAPPα), interferes with β-site APP-cleaving enzyme 1 (BACE1, β-secretase) cleavage and reduces amyloid-β (Aβ) generation. In an attempt to identify approaches to restore sAPPα levels, we found that human cord blood serum (CBS) significantly promotes sAPPα production compared with adult blood serum (ABS) and aged blood serum (AgBS) in Chinese hamster ovary cells stably expressing wild-type human APP. Interestingly, CBS selectively mediated the α-secretase cleavage of human neuron-specific recombinant APP₆₉₅ in a cell-free …

D-Cycloserine-Augmented One-Session Treatment Of Specific Phobias In Children And Adolescents, Lara J. Farrell, Allison M. Waters, Ella L. Oar, Evelin Tiralongo, Vinay Garbharran, Clair Alston-Knox, Harry Mcconnell, Nigel Collings, Melanie Zimmer-Gembeck, Caroline L. Donovan, Chris Testa, Eric A. Storch, Thomas H. Ollendick

Pediatrics Faculty Publications

Background: D-Cycloserine has potential to enhance exposure therapy outcomes. The current study presents a preliminary randomized, placebo-controlled double-blind pilot trial of DCS-augmented one-session treatment (OST) for youth (7–14 years) with specific phobia. A secondary aim of this pilot study was to explore the effects of youth age and within-session fear reduction as potential moderators of DCS outcomes in order to generate hypotheses for a larger trial. It was hypothesized that DCS would be associated with greater improvements than placebo, that children (7–10 years) would have greater benefits than adolescents (11–14 years), and that DCS effects would be stronger for participants …

Two Unrelated Patients With Autosomal Dominant Omodysplasia And Frizzled2 Mutations, Hannah E. Warren, Raymond J. Louie, Michael J. Friez, Jaime L. Frías, Jules G. Leroy, Jürgen W. Spranger, Steven A. Skinner, Neena L. Champaigne

Pediatrics Faculty Publications

No abstract provided.

Preclinical Pharmacokinetic Evaluation To Facilitate Repurposing Of Tyrosine Kinase Inhibitors Nilotinib And Imatinib As Antiviral Agents, Hari Krishna Ananthula, Scott Parker, Erin Touchette, R. Mark Buller, Gopi Patel, Daniel Kalman, Johanna S. Salzer, Nadia Gallardo-Romero, Victoria Olson, Inger K. Damon, Tessa Moir-Savitz, Larry Sallans, Milton H. Werner, Catherine M.T. Sherwin, Pankaj B. Dasai

Pediatrics Faculty Publications

Background

Several tyrosine kinase inhibitors (TKIs) developed as anti-cancer drugs, also have anti-viral activity due to their ability to disrupt productive replication and dissemination in infected cells. Consequently, such drugs are attractive candidates for “repurposing” as anti-viral agents. However, clinical evaluation of therapeutics against infectious agents associated with high mortality, but low or infrequent incidence, is often unfeasible. The United States Food and Drug Administration formulated the “Animal Rule” to facilitate use of validated animal models for conducting anti-viral efficacy studies.

Methods

To enable such efficacy studies of two clinically approved TKIs, nilotinib, and imatinib, we first conducted comprehensive pharmacokinetic …

Therapeutic Cocktail Approach For Treatment Of Hyperhomocysteinemia In Alzheimer’S Disease, Michael Leon, Darrell Sawmiller, R. Douglas Shytle, Jun Tan

Neurosurgery and Brain Repair Faculty Publications

In the United States, Alzheimer's disease (AD) is the most common cause of dementia, accompanied by substantial economic and emotional costs. During 2015, more than 15 million family members who provided care to AD patients had an estimated total cost of 221 billion dollars. Recent studies have shown that elevated total plasma levels of homocysteine (tHcy), a condition known as hyperhomocysteinemia (HHcy), is a risk factor for AD. HHcy is associated with cognitive decline, brain atrophy, and dementia; enhances the vulnerability of neurons to oxidative injury; and damages the blood–brain barrier. Many therapeutic supplements containing vitamin B12 and folate have …