Animals Commons^™

Cd44 Receptor Mediates Urate Crystal Phagocytosis By Macrophages And Regulates Inflammation In A Murine Peritoneal Model Of Acute Gout, Emira Bousoik, Marwa Qadri, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Gout is a chronic arthritis caused by the deposition of poorly soluble monosodium urate monohydrate (MSU) crystals in peripheral joints. Resident macrophages initiate inflammation in response to MSU mediated by NF-κB nuclear translocation and NLRP3 inflammasome activation. We investigated the role of CD44, a transmembrane receptor, in mediating MSU phagocytosis by macrophages. We used an antibody that sheds the extracellular domain (ECD) of CD44 to study the role of the receptor and its associated protein phosphatase 2A (PP2A) in macrophage activation. We also studied the significance of CD44 in mediating MSU inflammation in-vivo. Cd44^−/− BMDMs showed reduced MSU …

Assessing Morphology Of Iprgcs After Traumatic Brain Injury, Brian Foresi, Matt Smith

Williams Honors College, Honors Research Projects

ipRGCs are retinal ganglion cells that project to visual processing centers of the brain for nonimage forming visual functions. The relation of ipRGCs to tramatic brain injury (TBI) is emerging as data has been published describing ipRGC functional changes in TBI affected military veterans. Major symptomologies of concussions, a mild form of TBI, also overlap with the function governed by sites in the brain with major ipRGC projection percentages. Assesing if a morphological change is occuring in the ipRGCs after a TBI could support the idea of a pathological mechanism of the injury. This study could also indicate further relevance …

Molecular And Behavioral Mechanisms Mediated Paclitaxel-Induced Changes In Affect-Like Behavior In Mice, Julia Meade

Theses and Dissertations

Paclitaxel and oxaliplatin are two chemotherapeutics that cause acute neurotoxicity and chemotherapy-induce peripheral neuropathy (CIPN) in 70-90% of cancer patients. Chemotherapy-induced sensory changes are correlated with depression and anxiety. We characterized the effects of these drugs on sensation and various mood-related behaviors in mice, to determine if changes in sensation are associated with depression-like behavior, to explore putative mechanisms of chemotherapy-induced depression-like behavior (Aim 1), and to develop a mouse model of chemotherapy-induced operant responding deficit (Aim 2). In Aim 1, we observed that a cumulative dose of 32 mg/kg paclitaxel induced mechanical hypersensitivity and transiently reduced preference for sucrose …

Evaluation Of Tumor Necrosis Factor Alpha In Sleep-Deprived Menopausal- Induced Rats And The Impact On Bone Health, Nicole Ellsworth, Dwight Curry Iii, Cj Deleon, Frank Frisch

Student Scholar Symposium Abstracts and Posters

Post-menopausal osteoporosis as a consequence of estrogen depletion is a growing concern for women in the United States. As more women take on executive positions and experience sleep deprivation, there is the potential for up regulation of pro-inflammatory cytokines, such as tumor necrosis factor alpha. It follows that the homeostatic imbalance of osteoclastic and osteoblastic activity leads to a greater risk of disease. Bisphosphonates generally, and Zolendronate specifically works by decreasing the number of osteoclasts. This current study investigated the impact of Zolendronate on the concentrations of tumor necrosis factor alpha-type (TNFɑ) in 32 ovariectomized Wistar rats. Throughout a five …

Bone Strength And Distal Femur Trabecular Thickness In Sleep Deprived Ovariectomized Rats Treated With Zoledronate, Erin Nolte, Frank Frisch

Student Scholar Symposium Abstracts and Posters

Osteoporosis is a disease that causes the density and quality of bone to be decreased, which can increase the risk of fracture by 40%. 1 in 3 women over the age of 50 will be affected by osteoporosis. This study aimed to show how bone strength and distal femur trabecular thickness might be affected by Zoledronate and sleep-deprivation in estrogen-deficient rats. Wistar female rats were ovariectomized to contrive postmenopausal estrogen-deficiency. The rats were separated into 4 groups. The control group (C, n=4) was given an intraperitoneal (IP) injection of 0.45 mL of 0.9% saline, were housed in standard conditions permitting …

Graft Versus Host Disease-Associated Dry Eye: Role Of Ocular Surface Mucins And The Effect Of Rebamipide, A Mucin Secretagogue, Kiumars Shamloo, Ashley Barbarino, Saleh Alfuraih, Ajay Sharma

Pharmacy Faculty Articles and Research

PURPOSE. The present study was designed to investigate the role of ocular surface glycocalyx and mucins in graft versus host disease (GVHD)-associated dry eye. The ameliorative effect of topical rebamipide, a mucin secretagogue, on GVHD-associated dry eye was also tested.

METHODS. A mouse model of allogeneic transplantation was used to induce ocular GVHD with C57BL/6 as donors and B6D2F1 as recipient mice. Phenol red thread method and fluorescein staining was used to quantify tear secretion and corneal keratopathy. At 8 weeks after the allogeneic transplantation, corneas were harvested to perform glycocalyx staining and confocal microscopy. Goblet cell staining was performed …

Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas

Pharmacy Faculty Articles and Research

Recent evidence supports involvement of amylin and the amylin receptor in the pathogenesis of Alzheimer’s disease (AD). We have previously shown that amylin receptor antagonist, AC253, improves spatial memory in AD mouse models. Herein, we generated and screened a peptide library and identified two short sequence amylin peptides (12–14 aa) that are proteolytically stable, brain penetrant when administered intraperitoneally, neuroprotective against Aβ toxicity and restore diminished levels of hippocampal long term potentiation in AD mice. Systemic administration of the peptides for five weeks in aged 5XFAD mice improved spatial memory, reduced amyloid plaque burden, and neuroinflammation. The common residue SQELHRLQTY …

A Multivalent Kaposi Sarcoma-Associated Herpesvirus-Like Particle Vaccine Capable Of Eliciting High Titers Of Neutralizing Antibodies In Immunized Rabbits, David H. Mulama, Lorraine Z. Mustvunguma, Jennifer Totonchy, Peng Ye, Joslyn Foley, Gabriela M. Escalante, Esther Rodriguez, Ramina Nabiee, Murali Muniraju, Felix Wussow, Anne K. Barasa, Javier Gordon Ogembo

Pharmacy Faculty Articles and Research

Kaposi sarcoma-associated herpesvirus (KSHV) is an emerging pathogen and the causative agent of multiple cancers in immunocompromised patients. To date, there is no licensed prophylactic KSHV vaccine. In this study, we generated a novel subunit vaccine that incorporates four key KSHV envelope glycoproteins required for viral entry in diverse cell types (gpK8.1, gB, and gH/gL) into a single multivalent KSHV-like particle (KSHV-LP). Purified KSHV-LPs were similar in size, shape, and morphology to KSHV virions. Vaccination of rabbits with adjuvanted KSHV-LPs generated strong glycoprotein-specific antibody responses, and purified immunoglobulins from KSHV-LP-immunized rabbits neutralized KSHV infection in epithelial, endothelial, fibroblast, and B …

Investigation Into The Role Of Platelet Derived Growth Factor (Pdgf) In Type I Collagen Glomerulopathy, Isaac C. Springer

Graduate Theses/Dissertations

Progressive accumulation of collagen and extracellular matrix (ECM) proteins within renal glomeruli have implications for or result in renal fibrosis and glomerulosclerosis, with both events culminating in renal failure. To model this accumulation the Col1a2-deficient mouse model was used. The Col1a2-deficientmouse model is characterized by a mutation in the a2(I) chain, preventing incorporation into the type I collagen molecule. As a result, an α1(I) collagen chain incorporates into the collagen triple helix forming homotrimeric type I collagen, as opposed to heterotrimeric type I collagen. This change is due to the secondary wound healing response in response to ECM accumulation, …

Innate Chemical Resistance Of Virginia Big-Eared Bats (Corynorhinus Townsendii Virginianus) To White-Nose Syndrome, Daniel S. Danford, Leah Shriver, Hazel A. Barton

Williams Honors College, Honors Research Projects

White-nose Syndrome (WNS) is an emergent epidemic disease of bats in North America. Caused by the novel fungal pathogen Pseudogymnoascus destructans, with a mortality rate of >75%, in the last decade WNS has led to the local extinction of numerous bat species. Despite this high mortality, one species, the Virginia big-eared bat (Corynorhinus townsendii virginianus) remains unaffected. Virginia big-eared bats (VBEs) are commonly found covered in a yellow, oily substance, with a pelage commensal population dominated by the yeast, Debaryomyces udenii. As D. udenii is an oleaginous yeast that produces yellow colonies, the fungus may be responsible …

Of Rats And Men, Thomas S. Walsh

Capstones

This capstone is a data-driven investigation into New York City's rat problem. By using publicly available government data to map rat activity in NYC, I identified several socio-economic variables that correlate with rat populations at the community district, borough, and city-scale. I used these findings (mainly that rat problems are linked to lower incomes) as the basis of an investigation, which includes interviews with residents, experts, and city officials. Prof. Bobby Corrigan, urban rodentologist and formerly with the NYC Department of Health criticizes the city's efforts for the first time on the record.

https://thomasseiyawalsh.wixsite.com/ratstone

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …

Cyclic Ac253, A Novel Amylin Receptor Antagonist, Improves Cognitive Deficits In A Mouse Model Of Alzheimer’S Disease, Rania Soudy, Aarti Patel, Wen Fu, Kamaljit Kaur, David Mactavish, David Westaway, Rachel Davey, Jeffrey Zajac, Jack Jhamandas

Pharmacy Faculty Articles and Research

Introduction: Amylin receptor serves as a portal for the expression of deleterious effects of amyloid b-protein (Ab), a key pathologic hallmark of Alzheimer’s disease. Previously, we showed that AC253, an amylin receptor antagonist, is neuroprotective against Ab toxicity in vitro and abrogates Ab-induced impairment of hippocampal long-term potentiation.

Methods: Amyloid precursor protein–overexpressing TgCRND8 mice received intracerebroventricularly AC253 for 5 months. New cyclized peptide cAC253 was synthesized and administered intraperitoneally three times a week for 10 weeks in the same mouse model. Cognitive functions were monitored, and pathologic changes were quantified biochemically and immunohistochemically.

Results: AC253, when administered …

Selective Anticancer Activity Of Hydroxyapatite/Chitosan-Poly(D,L)-Lactide-Co-Glycolide Particles Loaded With An Androstane-Based Cancer Inhibitor, Nenad Ignjatović, Katarina M. Penov-Gaši, Victoria M. Wu, Jovana J. Ajduković, Vesna V. Kojić, Dana Vasiljević-Radović, Maja Kuzmanović, Vuk Uskoković, Dragab Uskoković

Pharmacy Faculty Articles and Research

In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. ¹H NMR and ¹³C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the …

Surveillance, Epidemiological, And Virological Detection Of Highly Pathogenic H5n1 Avian Influenza Viruses In Duck And Poultry From Bangladesh, Wahedul Karim Ansari, Md Safiullah Parvej, Mohamed E. El Zowalaty, Sally Jackson, Stephen A. Bustin, Adel K. Ibrahim, Md Tanvir Rahman, Han Zhang, Mohammad Ferdousur Rahman Khan, Md Mostakin Ahamd, Md. Fasiur Rahman, Marzia Rahman, Khm Nazmul H. Nazir, Sultan Ahmed, Md Liakot Hossenn, Md Abdul Kafi, Mat Yamage, Nitish C. Debnath, Graba Ahmed, Hossam Ashour, Md Masoud, Ayman Noreddin, Md B. Rahman

Pharmacy Faculty Articles and Research

Avian influenza viruses (AIVs) continue to pose a global threat. Waterfowl are the main reservoir and are responsible for the spillover of AIVs to other hosts. This study was conducted as part of routine surveillance activities in Bangladesh and it reports on the serological and molecular detection of H5N1 AIV subtype. A total of 2169 cloacal and 2191 oropharyngeal swabs as well as 1725 sera samples were collected from live birds including duck and chicken in different locations in Bangladesh between the years of 2013 and 2014. Samples were tested using virus isolation, serological tests and molecular methods of RT-PCR. …

Programming Heart Disease: Does Poor Maternal Nutrition Alter Expression Of Cardiac Markers Of Proliferation, Hypertrophy, And Fibrosis In Offspring?, Cathy Chun

Honors Scholar Theses

Maternal malnutrition can affect fetal organogenesis, metabolic processes, and factors involved in developmental regulation. Of the many physiological effects poor maternal nutrition can induce in offspring, one of the most important organs affected is the heart. Cardiovascular disease has been associated with poor maternal diet. It also been suggested that hypertension can originate during impaired intrauterine growth and development. Hypertension can trigger hypertensive heart disease and is associated with numerous heart complications. We hypothesized that poor maternal nutrition would alter critical growth factors associated with normal heart development, specifically, insulin-like growth factor (IGF)-1, IGF-2, transforming growth factor (TGF)β, and connective …

The Roles Of Malt1 In Nf-Κb Activation And Solid Tumor Progression, Deng Pan

Dissertations and Theses (Open Access)

The transcription factor NF-κB plays a central role in many aspects of biological processes and diseases, such as inflammation and cancer. Although it has been suggested thatNF-κB is critical in tumorigenesis and tumor progression, the molecular mechanism by which NF-κB is activated in solid tumor remains largely unknown. In the current work, we focus on growth factor receptor-induced NF-κB activation and tumor progression, including epidermal growth factor receptor (EGFR)-induced NF-κB in lung cancer and heregulin receptor (HER2)-induced NF-κB in breast cancer. We found that Mucosa-associated lymphoma translocation protein 1 (MALT1), also known as paracaspase, is required for EGFR-induced NF-κB activation …

Adult Gli2+/-;Gli3Δ699/+ Male And Female Mice Display A Spectrum Of Genital Malformation., Fei He, Pedram Akbari, Rong Mo, Jennifer J Zhang, Chi-Chung Hui, Peter C. Kim, Walid A Farhat

Surgery Faculty Publications

Disorders of sexual development (DSD) encompass a broad spectrum of urogenital malformations and are amongst the most common congenital birth defects. Although key genetic factors such as the hedgehog (Hh) family have been identified, a unifying postnatally viable model displaying the spectrum of male and female urogenital malformations has not yet been reported. Since human cases are diagnosed and treated at various stages postnatally, equivalent mouse models enabling analysis at similar stages are of significant interest. Additionally, all non-Hh based genetic models investigating DSD display normal females, leaving female urogenital development largely unknown. Here, we generated compound mutant mice, Gli2+/-;Gli3Δ699/+, …

Chronic Pancreatitis, Pain, And Anxiety In An Alcohol And High Fat Mouse Model, Tiffanie Clinkinbeard

Theses and Dissertations--Gerontology

Homeodynamic space (HDS) shrinks as vulnerability increases with aging and repeated damage to the cells. HDS is lost in alcoholic pancreatitis patients due to overconsumption of alcohol, smoking, and high fat diets. Etiologically relevant animal models for study of chronic pancreatitis (CP) are needed. In order to begin filling this gap a central purpose of this dissertation research was to examine relationships between the alcohol and high fat diet (AHF) and pancreatitis with attention to hypersensitivity and anxiety-like behaviors. The AHF diet induced pancreatitis described here etiologically mimics human risk factors of AHF consumption for advancement to alcoholic CP.

In …

Effects Of Pringle Maneuver And Partial Hepatectomy On The Pharmacokinetics And Blood–Brain Barrier Permeability Of Sodium Fluorescein In Rats, Mohammad K. Miah, Imam H. Shaik, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

Liver diseases are known to affect the function of remote organs. The aim of the present study was to investigate the effects of Pringle maneuver, which results in hepatic ischemia–reperfusion (IR) injury, and partial hepatectomy (Hx) on the pharmacokinetics and brain distribution of sodium fluorescein (FL), which is a widely used marker of blood–brain barrier (BBB) permeability. Rats were subjected to Pringle maneuver (total hepatic ischemia) for 20 min with (HxIR) or without (IR) 70% hepatectomy. Sham-operated animals underwent laparotomy only. After 15 min or 8 h of reperfusion, a single 25-mg/kg dose of FL was injected intravenously and serial …

Impact Of Starch Source On Equine Hindgut Microbial Ecology, Brittany Elizabeth Davis Harlow

Theses and Dissertations--Animal and Food Sciences

Grain inclusion in equine diets can allow starch to reach the hindgut where bacteria compete for the substrate. The hypothesis was that starch introduction would cause a source-dependent press disturbance in equine fecal microflora. Fecal cell suspensions were prepared by differential centrifugation and re-suspension in media with ground corn, oats or wheat. At 24 h, corn had more amylolytics and Group D Gram-positive cocci (GPC), and fewer lactate-utilizing (LU) bacteria and lactobacilli than oats, with wheat being intermediate. Predominant amylolytics were identified by their 16S RNA gene sequence as Enterococcus faecalis (corn, wheat) and Streptococcus bovis (oats). In an in …

Effects Of Intranasally Administered Dnsp-11 On The Central Dopamine System Of Normal And Parkinsonian Fischer 344 Rats, James H. Sonne

Theses and Dissertations--Neuroscience

Due to the blood-brain barrier, delivery of many drugs to the brain has required intracranial surgery which is prone to complication. Here we show that Dopamine Neuron Stimulating Peptide 11 (DNSP-11), following non-invasive intranasal administration, protects dopaminergic neurons from a lesion model of Parkinson’s disease in the rat. A significant and dose-dependent increase in an index of dopamine turnover (the ratio of DOPAC to dopamine) was observed in the striatum of normal young adult Fischer 344 rats by whole-tissue neurochemistry compared to vehicle administered controls.

Among animals challenged with a moderate, unilateral 6-hydroxy-dopamine (6-OHDA) lesion of the substantia nigra, those …

Hepatic Immunosuppressive Effects Of Systemically- Administered Novel Dextran-Methylprednisolone Prodrugs With Peptide Linkers In Rats, Imam H. Shaik, Hitesh K. Agarwal, Keykavous Parang, Reza Mehvar

Pharmacy Faculty Articles and Research

The hepatic immunosuppressive activities of two novel dextran prodrugs of methylprednisolone (MP) containing one (DMP1) or five (DMP5) amino acids as linkers were studied in rats. At various times (02 weeks) after intravenous administration of single 5 mg/kg (MP equivalent) doses of each prodrug or MP succinate (MPS), livers were isolated and immunologically stimulated ex vivo with lipopolysaccharide. The concentrations of tumor necrosis factor (TNF)-a in the outlet perfusate were then quantitated to assess immune response. Additionally, the concentrations of DMP1, DMP5, and/or MP were measured in the liver. MPS, DMP5, or DMP1 injections caused a maximum of 48.9%, 63.5%, …

Plasma Pharmacokinetics And Tissue Disposition Of Novel Dextran- Methylprednisolone Conjugates With Peptide Linkers In Rats, Suman Penugonda, Hitesh K. Agarwal, Keykavous Parang, Reza Mehvar

Pharmacy Faculty Articles and Research

The plasma and tissue disposition of two novel dextran prodrugs of methylprednisolone (MP) containing one (DMP-1) or five (DMP-5) amino acids as linkers were studied in rats. Single 5-mg/kg doses (MP equivalent) of each prodrug or MP were administered intravenously, and blood and tissue samples were collected. Prodrug and drug concentrations were quantitated using HPLC, and noncompartmental pharmacokinetic parameters were estimated. Whereas conjugation of MP with dextran in both prodrugs substantially decreased the clearance of the drug by ∼200-fold, the accumulations of the drug in the liver, spleen, and kidneys were significantly increased by conjugation. However, the extent of accumulation …

Effects Of Methylprednisolone And Its Liver-Targeted Dextran Prodrug On Ischemia–Reperfusion Injury In A Rat Liver Transplantation Model, Anjaneya Chimalakonda, Reza Mehvar

Pharmacy Faculty Articles and Research

Purpose. To evaluate the effectiveness of a liver-targeted dextran prodrug (DMP) of methylprednisolone ( MP) in cold preservation-warm reperfusion injury associated with liver transplantation.

Methods. The effects of donor pretreatment with single 5 mg/kg doses of MP or DMP on ischemia reperfusion damage to the liver were studied after 8 or 24 h of cold preservation in both isolated perfused rat liver (IPRL) and syngeneic orthotopic rat liver transplantation (OLT) models.

Results. In IPRL studies, donor pretreatment with DMP, and to a lesser degree MP, significantly improved the uptake of hyaluronic acid (HA), a marker of endothelial …

Attenuation Of Acute Rejection In A Rat Liver Transplantation Model By A Liver-Targeted Dextran Prodrug Of Methylprednisolone, Anjaneya Chimalakonda, Donald L. Montgomery, Jon A. Weidanz, Imam H. Shaik, Justin H. Nguyen, John J. Lemasters, Eiji Kobayashi, Reza Mehvar

Pharmacy Faculty Articles and Research

Background. The use of methylprednisolone (MP) and other corticosteroids for the treatment of acute liver allograft rejection is associated with severe toxicities in nontarget tissues. Therefore, selective delivery of NIP to the liver may improve its efficacy and alleviate its side effects. We investigated the effects of a novel liver-targeted dextran prodrug of MP (DMP) in an orthotopic rat liver transplantation (OLT) model.

Methods. The model consisted of a high responder rejection strain combination (Dark Agouti donors and Lewis recipients). Liver recipients were intravenously administered saline or a single subtherapeutic dose of MP (5 mg/kg) as the parent …