Medicine and Health Sciences Commons^™

Copd Exacerbation Biomarkers Validated Using Multiple Reaction Monitoring Mass Spectrometry, Janice M. Leung, Virginia Chen, Zsuzsanna Hollander, Darlene Dai, Scott J. Tebbutt, Shawn D. Aaron, Kathy L. Vandemheen, Stephen I. Rennard, J. Mark Fitzgerald, Prescott G. Woodruff, Stephen C. Lazarus, John E. Connett, Harvey O. Coxson, Bruce Miller, Christoph Borchers, Bruce M. Mcmanus, Raymond T. Ng, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) result in considerable morbidity and mortality. However, there are no objective biomarkers to diagnose AECOPD.

METHODS: We used multiple reaction monitoring mass spectrometry to quantify 129 distinct proteins in plasma samples from patients with COPD. This analytical approach was first performed in a biomarker cohort of patients hospitalized with AECOPD (Cohort A, n = 72). Proteins differentially expressed between AECOPD and convalescent states were chosen using a false discovery rate < 0.01 and fold change >1.2. Protein selection and classifier building were performed using an elastic net logistic regression model. The performance of the biomarker panel …

Clinical Profile And Containment Of The Ebola Virus Disease Outbreak In Two Large West African Cities, Nigeria, July-September 2014, Chima Ohuabunwo, Celestine Ameh, Oyin Oduyebo, Anthony Ahumibe, Bamidele Mutiu, Adebola Olayinka, Wasiu Gbadamosi, Erika Garcia, Carolina Nanclares, Wale Famiyesin, Abdulaziz Mohammed, Patrick Nguku, Richard I. Koko, Joshua Obasanya, Durojaye Adebayo, Yemi Gbadegesin, Oni Idigbe, Olukayode Oguntimehin, Sara Nyanti, Charles Nzuki, Ismail Abdus-Salam, Joseph Adeyemi, Nnanna Onyekwere, Emmanuel Musa, David Brett-Major, Faisal Shuaib, Abdulsalami Nasidi

Journal Articles: Epidemiology

INTRODUCTION: The Ebola virus disease (EVD) outbreak in Nigeria began when an infected diplomat from Liberia arrived in Lagos, the most populous city in Africa, with subsequent transmission to another large city.

METHODS: First-, second-, and third-generation contacts were traced, monitored, and classified. Symptomatic contacts were managed at Ebola treatment centers as suspected, probable, and confirmed EVD cases using standard operating procedures adapted from the World Health Organization EVD guidelines. Reverse transcription PCR tests confirmed EVD. Socio-demographic, clinical, hospitalization, and outcome data of the July-September 2014 Nigeria EVD cohort were analyzed.

RESULTS: The median age of the 20 EVD cases …

Emerging Technologies To Measure Neighborhood Conditions In Public Health: Implications For Interventions And Next Steps, M. Schootman, E. J. Nelson, K. Werner, E. Shacham, M. Elliott, Kendra Ratnapradipa, M. Lian, A. Mcvay

Journal Articles: Epidemiology

Adverse neighborhood conditions play an important role beyond individual characteristics. There is increasing interest in identifying specific characteristics of the social and built environments adversely affecting health outcomes. Most research has assessed aspects of such exposures via self-reported instruments or census data. Potential threats in the local environment may be subject to short-term changes that can only be measured with more nimble technology. The advent of new technologies may offer new opportunities to obtain geospatial data about neighborhoods that may circumvent the limitations of traditional data sources. This overview describes the utility, validity and reliability of selected emerging technologies to …

Maporal Hantavirus Causes Mild Pathology In Deer Mice (Peromyscus Maniculatus), Amanda Mcguire, Kaitlyn Miedema, Joseph R. Fauver, Amber Rico, Tawfik Aboellail, Sandra L. Quackenbush, Ann Hawkinson, Tony Schountz

Journal Articles: Epidemiology

Rodent-borne hantaviruses can cause two human diseases with many pathological similarities: hantavirus cardiopulmonary syndrome (HCPS) in the western hemisphere and hemorrhagic fever with renal syndrome in the eastern hemisphere. Each virus is hosted by specific reservoir species without conspicuous disease. HCPS-causing hantaviruses require animal biosafety level-4 (ABSL-4) containment, which substantially limits experimental research of interactions between the viruses and their reservoir hosts. Maporal virus (MAPV) is a South American hantavirus not known to cause disease in humans, thus it can be manipulated under ABSL-3 conditions. The aim of this study was to develop an ABSL-3 hantavirus infection model using the …

Early Identification And Prevention Of The Spread Of Ebola - United States, Chris A. Van Beneden, Harald Pietz, Robert D. Kirkcaldy, Lisa M. Koonin, Timothy M. Uyeki, Alexandra M. Oster, Deborah A. Levy, Maleeka Glover, Matthew J. Arduino, Toby L. Merlin, David T. Kuhar, Christine Kosmos, Beth P. Bell

Journal Articles: Epidemiology

In response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa, CDC prepared for the potential introduction of Ebola into the United States. The immediate goals were to rapidly identify and isolate any cases of Ebola, prevent transmission, and promote timely treatment of affected patients. CDC's technical expertise and the collaboration of multiple partners in state, local, and municipal public health departments; health care facilities; emergency medical services; and U.S. government agencies were essential to the domestic preparedness and response to the Ebola epidemic and relied on longstanding partnerships. CDC established a comprehensive response that included two new …

Vector Competence Of American Mosquitoes For Three Strains Of Zika Virus, James Weger-Lucarelli, Claudia Rückert, Nunya Chotiwan, Chilinh Nguyen, Selene M. Garcia Luna, Joseph R. Fauver, Brian D. Foy, Rushika Perera, William C. Black, Rebekah C. Kading, Gregory D. Ebel

Journal Articles: Epidemiology

In 2015, Zika virus (ZIKV; Flaviviridae; Flavivirus) emerged in the Americas, causing millions of infections in dozens of countries. The rapid spread of the virus and the association with disease outcomes such as Guillain-Barré syndrome and microcephaly make understanding transmission dynamics essential. Currently, there are no reports of vector competence (VC) of American mosquitoes for ZIKV isolates from the Americas. Further, it is not clear whether ZIKV strains from other genetic lineages can be transmitted by American Aedes aegypti populations, and whether the scope of the current epidemic is in part facilitated by viral factors such as enhanced replicative fitness …

Plasmodium Falciparum Infection Status Among Children With Schistosoma In Sub-Saharan Africa: A Systematic Review And Meta-Analysis, Abraham Degarege, Dawit Degarege, Emir Veledar, Berhanu Erko, Mathieu Nacher, Consuelo M. Beck-Sague, Purnima Madhivanan

Journal Articles: Epidemiology

BACKGROUND: It has been suggested that Schistosoma infection may be associated with Plasmodium falciparum infection or related reduction in haemoglobin level, but the nature of this interaction remains unclear. This systematic review synthesized evidence on the relationship of S. haematobium or S. mansoni infection with the occurrence of P. falciparum malaria, Plasmodium density and related reduction in haemoglobin level among children in sub-Saharan Africa (SSA).

METHODOLOGY/PRINCIPAL FINDINGS: A systematic review in according with PRISMA guidelines was conducted. All published articles available in PubMed, Embase, Cochrane library and CINAHL databases before May 20, 2015 were searched without any limits. Two reviewers …

Plasmodium Falciparum And Soil-Transmitted Helminth Co-Infections Among Children In Sub-Saharan Africa: A Systematic Review And Meta-Analysis, Abraham Degarege, Emir Veledar, Dawit Degarege, Berhanu Erko, Mathieu Nacher, Purnima Madhivanan

Journal Articles: Epidemiology

BACKGROUND: The epidemiology of soil-transmitted helminth (STH) and Plasmodium co-infections need better understanding. The findings of the individual studies are inconclusive. A systematic review was conducted to synthesize evidence on the association of STH infection with the prevalence and density of Plasmodium falciparum infection, and its effect on anaemia among children in sub-Saharan Africa (SSA).

METHODS: Relevant studies published before March 6, 2015 were identified by searching Medline (via Pubmed), Embase, Cochrane Library and CINAHL without any language restriction. Studies on P. falciparum and STH co-infection among children in SSA except for case studies were included in this study. Studies …

Assessment Of Clarias Gariepinus As A Biological Control Agent Against Mosquito Larvae, Buze Chala, Berhanu Erko, Abebe Animut, Abraham Degarege, Beyene Petros

Journal Articles: Epidemiology

BACKGROUND: The emergence and spread of insecticide resistant mosquitoes renewed interest in investigating the use of larvivorous fish as a biological control agent. The potential of Clarias gariepinus fish in controlling Anopheles arabiensis and culicine larvae was assessed under laboratory and semi-field conditions.

RESULTS: Small size (15-20 cm) C. gariepinus fish consumed greater number of mosquito larvae than the large size fish (25-40 cm) in the multivariate regression model (β = 13.36, 95 % CI = 4.57, 22.15). The Anopheles larvae consumed was greater in number than the culicines larvae consumed by the fish (β = 12.10, 95 % CI …

Age‐Related Changes In Cerebellar And Hypothalamic Function Accompany Non‐Microglial Immune Gene Expression, Altered Synapse Organization, And Excitatory Amino Acid Neurotransmission Deficits, Stephen J. Bonasera, Jyothi Arikkath, Michael D. Boska, Tammy R. Chaudoin, Nicholas W. Dekorver, Evan H. Goulding, Traci A. Hoke, Vahid Mojtahedzedah, Crystal D. Reyelts, Balasrinivasa R. Sajja, A. Katrin Schenk, Laurence H. Tecott, Tiffany A. Volden

Data: Geriatrics

No abstract provided.

Comparing Biocompatibility Of Ibad-Produced Nano-Films Of Titanium Oxide With Orthopaedic Grade Titanium, Raheleh Miralami

Posters and Presentations: Orthopaedic Surgery & Rehab

Titanium (Ti) is the material of choice for orthopaedic applications because it is biocompatible and encourages osteoblast growth. The present study was devised to compare the osteoblast functions on nano-crystalline titanium oxide films produced by an ion beam assisted deposition (IBAD) technique with the osteoblast functions on micro-crystalline orthopaedic-grade titanium. To characterize the biocompatibility of these surfaces, we have studied cell adhesion, growth, and differentiation on different samples. Cell responses to surfaces were examined using the human osteosarcoma cell line (SAOS-2) with osteoblastic properties. To compare cell adhesion and growth, DAPI-stained nuclei were counted using ImageJ and Metamorph software. Immunofluorescence …

Effect Of Anthelminthic Treatment On Helminth Infection And Related Anaemia Among School-Age Children In Northwestern Ethiopia, Yonas Yimam, Abraham Degarege, Berhanu Erko

Journal Articles: Epidemiology

BACKGROUND: Information about improvements in the health status of population at-risk of helminth infection after anthelminthic treatment helps to evaluate the effectiveness of the large scale deworming program. The objectives of this study were to assess the impact of anthelminthic treatment on the prevalence and intensity of intestinal helminth infection, haemoglobin level and prevalence of anaemia among school-age children.

METHODS: A total of 403 children attending Tikur Wuha Elementary School in Jiga, northwestern Ethiopia were enrolled in this study between February and March 2011. Formol-ether concentration and Kato-Katz methods were used to examine stool for intestinal helminth infections at baseline …

Epidemiology Of Plasmodium And Helminth Coinfection And Possible Reasons For Heterogeneity, Abraham Degarege, Berhanu Erko

Journal Articles: Epidemiology

Understanding the impact of helminth infections on clinical malaria is useful for designing effective malaria control strategies. Plenty of epidemiological studies have been conducted to unravel the nature of interactions between Plasmodium and helminth infection. Careful broad summarization of the existing literature suggests that Schistosoma mansoni and hookworm infections may increase the risk of clinical malaria and associated morbidities, but Trichuris trichiura infection is not associated with the occurrence of clinical malaria and related outcomes. However, findings about effect of Ascaris lumbricoides and Schistosoma haematobium infection on clinical malaria are contradictory. Furthermore, the nature of relationship of helminth infection with …

Are You Pepped And Prepped For Travel? Risk Mitigation Of Hiv Infection For Travelers, David Brett-Major, P. T. Scott, T A. Crowell, C. S. Polyak, K. Modjarrad, M. L. Robb, D. L. Blazes

Journal Articles: Epidemiology

The HIV pandemic persists globally and travelers are at risk for infection by the Human Immunodeficiency Virus (HIV). While HIV-focused guidelines delineate risk stratification and mitigation strategies for people in their home communities, travel issues are not addressed. In this review, direct and indirect evidence on HIV risk among travelers is explored. The burgeoning practice of employing pre-exposure prophylaxis (PrEP) with anti-retroviral therapy in the non-travel setting is introduced, as well as the more established use of post-exposure prophylaxis (PEP). Challenges in applying these lessons to travelers are discussed, and a new guidelines process is scoped and recommended.

Dysfunctional Epileptic Neuronal Circuits And Dysmorphic Dendritic Spines Are Mitigated By Platelet-Activating Factor Receptor Antagonism, Alberto E. Musto, Robert F. Rosencrans, Chelsey P. Walker, Surjyadipta Bhattacharjee, Chittalsinh M. Raulji, Ludmila Belayev, Zhide Fang, William C. Gordon, Nicolas G. Bazan

Journal Articles: Pediatrics

Temporal lobe epilepsy or limbic epilepsy lacks effective therapies due to a void in understanding the cellular and molecular mechanisms that set in motion aberrant neuronal network formations during the course of limbic epileptogenesis (LE). Here we show in in vivo rodent models of LE that the phospholipid mediator platelet-activating factor (PAF) increases in LE and that PAF receptor (PAF-r) ablation mitigates its progression. Synthetic PAF-r antagonists, when administered intraperitoneally in LE, re-establish hippocampal dendritic spine density and prevent formation of dysmorphic dendritic spines. Concomitantly, hippocampal interictal spikes, aberrant oscillations, and neuronal hyper-excitability, evaluated 15-16 weeks after LE using multi-array …

Cellular Responses And Tissue Depots For Nanoformulated Antiretroviral Therapy., Andrea L. Martinez-Skinner, Mariluz Araínga, Pavan Puligujja, Diana L. Palandri, Hannah M. Baldridge, Benson J. Edagwa, Joellyn Mcmillan, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes serve as the macrophage subcellular depots, little is known of the dynamics of nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, drug uptake and distribution following both intraperitoneal and intramuscular injection of nanoformulated atazanavir (nanoATV). Local inflammatory responses heralded drug distribution to peritoneal cell populations, regional lymph nodes, spleen and liver. This proceeded for three days in male Balb/c mice. NanoATV-induced changes in myeloid populations were assessed by fluorescence-activated cell sorting (FACS) with CD45, …

Cellular Responses And Tissue Depots For Nanoformulated Antiretroviral Therapy., Andrea L. Martinez-Skinner, Mariluz Araínga, Pavan Puligujja, Diana L. Palandri, Hannah M. Baldridge, Benson J. Edagwa, Joellyn Mcmillan, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes serve as the macrophage subcellular depots, little is known of the dynamics of nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, drug uptake and distribution following both intraperitoneal and intramuscular injection of nanoformulated atazanavir (nanoATV). Local inflammatory responses heralded drug distribution to peritoneal cell populations, regional lymph nodes, spleen and liver. This proceeded for three days in male Balb/c mice. NanoATV-induced changes in myeloid populations were assessed by fluorescence-activated cell sorting (FACS) with CD45, …

Squamous Cell Carcinoma Response To Cisplatin Exposure, Khanh V. Luong

Theses & Dissertations

Purpose: This thesis attempted to quantitatively analyze the individual cell fate choice in resistant head and neck UM-SCC38 cells exposed to cisplatin using the most current techniques available.

Methods: UM-SCC-38 cells were grown in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% fetal bovine serum (FBS). They were treated with cisplatin and ATM/ATR inhibitors of known dosages. Using live cell imaging, one hundred cells were tracked in each experiment and their behaviors were analyzed and entered into Microsoft Excel Spreadsheet to generate cell profile graphs. HaCaT cells, non-tumorigenic keratinocyte cell line, were also analyzed using live cell imaging and their …

The Effect Of Body Mass Index On Graft Function And Kidney Transplant Outcomes, Morgan Galle

Theses & Dissertations

Background: When determining eligibility for kidney transplantation, body mass index (BMI) is often a debatable criterion for transplant due to the clinical indication, an elevated BMI has adverse effects on kidney transplant outcomes. There is a current gap in research on the effect BMI has on kidney transplant outcomes.

Purpose: The purpose of this study was to determine the role BMI plays in post-kidney transplant clinical outcomes including delayed graft function, new onset diabetes after transplant, wound complications, hospital length of stay, albumin, and readmissions to the hospital from initial hospitalization and at six months following kidney transplantation. The primary …

Biodegradable Hybrid Nanogels For Combination Chemotherapy, Swapnil Desale

Theses & Dissertations

Combination chemotherapy is commonly used to treat cancer, because such a therapy regimens usually involve sequential administration of multiple drugs and allow targeting different cell signaling pathway. The co-delivery of drug combination at a controlled ratio via the same vehicle is offering the advantages such as spatial-temporal synchronization of drug exposure, synergistic therapeutic effects and suppression of drug resistance. Undoubtedly, there are several molecular and pharmacological factors that determine the effectiveness of drug combinations. A rationally designed drug combination is required since certain drug ratios and the definitive exposure to the targets of interest can only be synergistic while others …

Evaluation Of Upper Airway Changes Following Surgical Removal Of The Adenoids Using 3-D Cone Beam Ct, Christopher C. Schultz

Theses & Dissertations

Purpose: The purpose of this study was to evaluate the changes in volume, cross-sectional area and depth of the upper airway following the surgical removal of the adenoids.

Materials and Methods: 16 patients were diagnosed with hypertrophic adenoids and referred for surgical removal. Pre-surgical and post-surgical CBCT scans were taken on each patient. Volume measurements of the total airway, oropharynx and nasopharynx were recorded. In addition, cross-sectional areas and airway depths at the posterior nasal spine (PNS) and cervical vertebrae 2 were recorded. 15 patients diagnosed with no or mild adenoid hypertrophy were treated as the control group. The controls …

The Feedforward And Feedback Controls On Gait In Adults With Diabetes, Chun-Kai Huang

Theses & Dissertations

There are nearly 26 million people with diabetes mellitus (DM) in the US, and half of chronic DMs develop somatosensory deficits due to diabetic polyneuropathy or diabetic peripheral neuropathy (DPN). The absence or impaired somatosensory feedback (e.g. touch sensation or joint proprioception) resulted from the damage of large nerve fiber, and motor deficits such as attenuated muscle strength and abnormal plantar pressure of lower extremity have been identified in DPN, and these sensorimotor impairments lead to an increased number of falls. To reduce the risk of falling, a well-coordinated and adapted limb movement driven by the feedforward (anticipatory) and feedback …

Examining Employee Knowledge Of The Jennie Edmundson Hospital Active Shooter Policy, Mallory W. Darais

Theses & Dissertations

Nationally, there has been a large increase in the number of active shooter events within healthcare facilities such as hospitals. Due to this increase, government organizations have recently released documents to guide healthcare facilities on implementing active shooter policies and updating emergency operation plans. Currently, recommendations from government entities such as the Federal Bureau of Investigation and the Department of Homeland Security suggest the “Run, Hide, Fight” approach during an active shooter incident. Jennie Edmundson Hospital, located in Council Bluffs, Iowa, and affiliated with the Methodist Health System, currently has an active shooter policy in place. Data was collected from …

Epacs: Epigenetic Regulators That Affect Cell Survival In Cancer., Catherine Murari

Theses & Dissertations

Cyclic adenosine monophosphate (cAMP) is a second messenger responsive to many external stimuli, playing an important role in cellular gene expression, metabolism, migration, differentiation, hypertrophy, apoptosis and secretion. All of these cellular functions are important in many diseases including cancer. Most of its effects were initially attributed to the classical protein kinase A (PKA) protein, but cellular functions such as proliferation and migration were found to be PKA independent and dependent on the newly discovered exchange proteins directly activated by cAMP (EPACs). EPACs are single polypeptides that primarily function as guanine exchange factors (GEFs) for Rap proteins that allow the …

Postural Responses To Perturbations Of The Vestibular System During Walking In Healthy Young And Older Adults, Jung Hung Chien

Theses & Dissertations

It has been shown that approximate one-third of US adults aged 40 years and older (69 million US citizens) have some type of vestibular problems. These declining abilities of the vestibular system affect quality of life. Difficulties in performing daily activities (dressing, bathing, getting in and out of the bed and etc.) have been highly correlated to loss of balance due to vestibular disorders. The exact number of people affected by vestibular disorders is still difficult to quantify. This might be because symptoms are difficult to describe and differences exist in the qualifying criteria within and across studies. Thus, it …

Antiviral Peptide Nanocomplexes As Potential Therapeutics For The Treatment Of Infectious Diseases, Jinjin Zhang

Theses & Dissertations

Hepatitis C Virus (HCV) is recognized as a major burden in global public health, which can be further exacerbated by several cofactors such as human immunodeficiency virus (HIV). Currently, there is no vaccine for HCV. The emergence of potent and highly specific direct-acting antivirals (DAA) has marked a new era in HCV therapy, however, the remaining issues like affordability, genotype dependency, and potential resistance still necessitate the development of additional therapeutic approaches to be used instead or in combination with DAA.

Recently, the antiviral peptide C5A (in our studies designated as p1) and its cationic derivative p41 have been identified …

The Role Of Genetic Alterations In Tumor Initiation, Progression And Transformation, Weiwei Zhang

Theses & Dissertations

Follicular lymphoma (FL) is the second most common lymphoma in the United States. Although it is generally an indolent lymphoma, FL is not curable, and, in about 30% of patients, the FL undergoes transformation into an aggressive lymphoma (tFL) with marked worsening of prognosis. To identify mutations preferentially present in tFL, we performed whole exome sequencing (WES) on paired FL and tFL arising in the same patients and developed a mutational analysis pipeline. After we identified potentially important genes that have been found to be mutated in our paired FL and tFL study, we constructed a custom capture platform including …

Regulatory Roles Of Mical-L1 And Ehd1 In Cell Signaling And Mitosis, James B. Reinecke

Theses & Dissertations

Membrane trafficking is a basic cell biological process that controls the distribution of proteins and lipids. Our lab is particularly interested in delineating the cellular functions as well as the molecular mechanisms that regulate the C-terminal Eps15 Homology Domain (EHD) protein family of adenosine-5’-triphosphatases in mammalian cells. EHD1-4 are ubiquitously expressed in mammalian tissues and serve partially overlapping but also distinct functions in regulating membrane shaping and fission along the endocytic pathway. Specifically, EHD1 is recruited to tubular recycling endosomes (TREs) by Molecule Interacting with CasL Like-1 (MICAL-L1) and facilitates TRE fission and release of cargo from the perinuclear endocytic …

Interaction Between Angiotensin Ii And Bdnf In Modulating Sympathetic Nerve Activity, Bryan K. Becker

Theses & Dissertations

Over activation of the sympathetic nervous system is prevalent in many forms of cardiovascular disease such as chronic heart failure (CHF) and hypertension. Although increased neuronal renin-angiotensin system activity in presympathetic neurons has been well implicated in mediating this sympatho-excitation, many of the neuronal effects of angiotensin II (Ang II) signaling remain poorly understood. One particular mechanism of Ang II-mediated increases in presympathetic neuronal activity is through reductions in voltage-gated K⁺ currents. Another pathway that has profound effects on neuronal K⁺ currents and that has been previously implicated in Ang II-signaling is brain-derived neurotrophic factor (BDNF) activity through …

Selective Vip Receptor Agonists Facilitate Immune Transformation For Dopaminergic Neuroprotection In Mptp-Intoxicated Mice., Katherine E. Olson, Lisa M. Kosloski-Bilek, Kristi M. Anderson, Breha J. Diggs, Barbara E. Clark, John M. Gledhill, Scott J. Shandler, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

UNLABELLED: Vasoactive intestinal peptide (VIP) mediates a broad range of biological responses by activating two related receptors, VIP receptor 1 and 2 (VIPR1 and VIPR2). Although the use of native VIP facilitates neuroprotection, clinical application of the hormone is limited due to VIP's rapid metabolism and inability to distinguish between VIPR1 and VIPR2 receptors. In addition, activation of both receptors by therapeutics may increase adverse secondary toxicities. Therefore, we developed metabolically stable and receptor-selective agonists for VIPR1 and VIPR2 to improve pharmacokinetic and pharmacodynamic therapeutic end points. Selective agonists were investigated for their abilities to protect mice against MPTP-induced neurodegeneration …