Medicine and Health Sciences Commons^™

Exploring The Design Space Of Antifungal Peptides, Miryam Kikhwa

Seton Hall University Dissertations and Theses (ETDs)

The synthesis, characterization, and evaluation of antifungal activity of peptides FQ15 and FG10 will be conducted to address the hypothesis. The hypothesis of this thesis is that a peptide with similar properties to AS15 would have similar activity against Cryptococcus neoformans. This study addresses the challenge of drug- resistant microbes by developing inhibitors targeting lipid flippase and exploring their potential as antimicrobial agents against Cryptococcus neoformans. Chapter 1 provides a historical context of the background on the development of antimicrobials and common antifungal treatments, as well as an introduction about C. neoformans and its resistance mechanism. Chapter 2 introduces the …

Synthesis, Characterization And Biological Evaluation Of Polyarginine Derived Bone-Targeting Peptides, Gina L. Antuono

Seton Hall University Dissertations and Theses (ETDs)

Osteoblast-targeting peptides in the treatment of bone disease is a new and novel approach to offering effective treatment of various cancers and can be used in bio-medical, medicinal chemistry and biotechnology applications. By targeting adhesion proteins produced by osteoblast cells, certain cancers which migrate and metastasize to the bone may be more effectively treated. An osteoblast-targeting peptide composed of Ser-Asp-Ser-Ser-Asp (SDSSD) which selectively binds to osteoblast cells via periostin has recently been identified. This peptide was functionalized with polyurethane, generating nanomicelles which encapsulated RNA for the therapeutic treatment of osteoporosis. This study has served as the basis for the research …

Flippase Inhibitors As Antimicrobial Agents, Robert Tancer

Seton Hall University Dissertations and Theses (ETDs)

Drug resistant microbes are a considerable challenge for modern medicine to overcome. The research described in this dissertation involved development of lipid flippase inhibitors and investigating their potential as antimicrobial agents against various drug resistant microbes. The microbes primarily investigated were methicillin resistant Staphylococcus aureus (MRSA) & Cryptococcus neoformans. Chapter 1 reviews the historical perspective and summarizes the current state of the field of research. In Chapter 2, the design space of an antimicrobial peptide known as humimycin was explored and the effects of modifications on its structure were observed against MRSA. Several key observations resulted. Most notably, the …

Clinically Relevant Dosage Of Vancomycin Does Not Negatively Impact Periosteum Derived Osteoblast Precursor Cellular Functions, Alexis Hernandez

Seton Hall University Dissertations and Theses (ETDs)

Surgical site infections (SSI) can develop post-operatively and carry significant clinical and financial implications. SSI can carry a cost of up to $30,000 per case, as well as an estimated 6 day longer hospitalization. Patients with Type II Diabetes (DM) have an increased susceptibility to infection and suffer from poor bone healing overall. Therefore, diabetic patients who have undergone orthopedic surgery risk both an increased chance of developing an SSI as well as suboptimal bone healing. Vancomycin and other antibiotics have traditionally been used prophylactically to prevent infection, however the effect of vancomycin on bone healing in a diabetic population …

A Functional Three-Dimensional Microphysiological Model Of Myeloma Bone Disease, Richard Visconti

Seton Hall University Dissertations and Theses (ETDs)

Multiple myeloma (MM) is a hematologic cancer caused by a mature B cell neoplasm, or plasmacytoma, that infiltrates the skeleton at several sites. The disease is characterized by uninhibited transformed plasma cell proliferation that disrupts skeletal homeostasis leading to decreased bone modeling and increased bone resorption. Osteolytic lesions (OL) or voids left in the bone, remain long after the treatment of the cancer and indicate disease progression to myeloma bone disease (MBD). Current combinatorial MM therapies inhibit malignant plasma cell proliferation, slow the progression towards MBD, and increase the mean five-year survival rate, but do little to improve osteoblastic function …

Vanadium Compounds Modulate Osteoblast Proliferation And Function, Bryan Sosa

Seton Hall University Dissertations and Theses (ETDs)

Osteoblastogenesis is an essential part of the bone healing process. Insulin has been shown to improve bone healing in both normal and diabetic bone healing models. In addition, insulin mimetic compounds such as Zinc chloride (ZnCl₂) and Vanadyl acetylacetonate (VAC) have also been shown to improve bone healing in these models as well. The purpose of this study was to determine the effects of vanadium compounds VAC and Vanadium (II) sulfate (VSO₄) in osteoblast proliferation and function. In addition the mechanisms by which growth and function are facilitated by these Vanadium compounds were also evaluated. In …

Zinc Chloride Enhanced Chondrogenesis Is Vegf Dependent, Gilbert M. Sharp Iv

Seton Hall University Dissertations and Theses (ETDs)

Researchers have begun investigating whether insulin mimetics such as ZnCl2 could promote bone healing in both non-diabetic and diabetic fracture healing similarly to insulin. Our research focused on understanding the mechanism by which ZnCl2 affects chondrogenesis, an important component of bone fracture healing. The increases in proteoglycan deposition and cell proliferation seen in our data may be a result of ZnCl2 induction of the IGF-1 pathway. When the VEGF pathway was inhibited in ZnCl2- or insulin-treated cells significant decreases in proteoglycan deposition occurred on day 7 and 14 (P=0.007 for ZnCl2, P=0.028 for insulin) when compared to controls. This data …

Fluorescently Labeled Sirnas And Their Theranostic Applications In Cancer Gene Therapy, Stephen David Kozuch

Seton Hall University Dissertations and Theses (ETDs)

Gene therapy has emerged as a promising precision nano-medicine strategy in the treatment of numerous diseases including cancer. At the forefront of its utility are the applications of short-interfering RNA (siRNA), that silence oncogenic mRNA expression leading to cancer cell death through the RNA interference (RNAi) pathway. Despite the therapeutic potential, siRNAs are limited by poor pharmacological properties, which has hindered their translation into the clinic. Recent studies, however, have highlighted the applications of modified siRNAs, including the use of fluorescent probes and siRNA nanostructures in cancer detection and treatment. The siRNAs reported in this thesis are designed to target …

Effects Of Direction Time Constraints And Walking Speed On Turn Strategies And Gait Adaptations In Healthy Older And Young Adults, Dennis Torre

Seton Hall University Dissertations and Theses (ETDs)

Hip fractures can be life-threatening, debilitating, and costly. The odds for hip fracture increases from impact of sideways falls. While turning has been strongly associated with hip fracture & sideways falls, the distinction between the risks for walking-turns as opposed to low-velocity in-place turning is not clear. The present study sought to fill a gap as previous research had not compared walking-turn performance in young & healthy older adults at low-fall risk within the same study and response-conditions of speed interacting with direction-cue time constraints. Spatial-temporal variables representative of AP braking/propulsion (i.e. stride-length & speed) & ML stability (left/right H-H …

Synthesis And Evaluation Of A Novel Carbohydrate Template And Analogs Thereof For Potential Cns-Active Drugs, Emi Hanawa-Romero

Seton Hall University Dissertations and Theses (ETDs)

Central nervous system (CNS) disorders are becoming a major societal problem. Examples of well-known CNS disorders are: neurodegenerative disorders such as Parkinson's, Huntington's and Alzheimer’s diseases, epilepsy/seizures, addiction, bipolar disorder, catalepsy, meningitis, migraines, attention deficit/hyperactivity disorder (ADHD), and multiple sclerosis. CNS disorders can be caused by various factors and therefore can affect ages, genders and races of all.

The population of patients with CNS disorders is increasing and a significant percentage of patients have symptoms that are not controlled by existing treatments. In addition, since CNS disorders are chronic disorder, there is no cure and thus the patients have to …

Diversity Oriented Synthesis, Characterization And Anti-Cancer Activity Of Killer Peptide Nucleolipid Bioconjugates, Niki K. Rana

Seton Hall University Dissertations and Theses (ETDs)

The killer peptide sequence D-(KLAKLAK)₂ has been originally designed and developed as an antibacterial agent. Despite having excellent cytotoxicity towards bacteria, this sequence maintains low cell cytotoxity in malignant mammalian cell types such as cancer. The chemical basis for its selectivity has been attributed to its poly(cationic) amphiphilic nature, which facilitates cell permeability across the negatively charged bacterial membrane, but with limited permeability across the zwitterionic membrane of mammalian cells. The positively charged D-(KLAKLAK)₂ sequence has been found to accumulate on the surface of the mitochondria causing dissipation of the negatively charged mitochondrial membrane potential. This charge disruption …

B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips

Seton Hall University Dissertations and Theses (ETDs)

Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory cytokines such …

Comparative Evaluation Of The Antibacterial, Anti-Biofilm And Anti-Spore Effects Of Theaflavins And Palmitoyl-Egcg, Gabriella M. Appice

Seton Hall University Dissertations and Theses (ETDs)

Tea, one of the most common beverages, originates from the leaves of the Camellia sinensis plant. Two major groups of tea are fermented black tea and unfermented green tea. Theaflavins (TFs) are the major polyphenols present in black tea, while mono-palmitoyl-epigallocatechin-gallate (pEGCG) is a modified green tea polyphenol. In this study, the antibacterial effects of TF and pEGCG were evaluated against six selected bacteria, Staphylococcus epidermidis, Streptococcus mutans, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa and Proteus vulgaris, using an antibacterial assay. A viability assay using SYTOX® staining and flow cytometry was also used to determine the effect of these compounds …

Exploring Knowledge, Beliefs And Practices Of Radon Gas Exposure Among Public Health Workers, Paschal Nwako

Seton Hall University Dissertations and Theses (ETDs)

Radon gas exposure is the highest cause of lung cancer among people that never smoked in the United States. People exposed to elevated levels of radon had a higher risk of developing lung cancer. Achieving the long term goal of the Indoor Radon Abatement Act (IRAA) of 1988 require a combined efforts of government agencies. Public health workers are change agents and their role in protecting and improving the health of their communities are well documented. This study created and utilized a multi question survey, the Public Health Workers Radon Assessment Instrument (PHWRAI) to explore knowledge, beliefs, personal and professional …

Exploring Barriers To The Adoption Of Pharmacogenomic Technology In The Clinical Setting By Clinical Healthcare Providers, Jason Sudia

Seton Hall University Dissertations and Theses (ETDs)

The changing landscape of healthcare in the US has created new questions about how to best provide cost-effective, individualized care. Personalized medicine and more specifically, pharmacogenomic technology have offered new tools for healthcare providers to use to increase the efficacy, safety, and cost-effectiveness of care. However, these tools are not being utilized to their predicted extent in the clinical setting. This study utilized Rogers’ Diffusion of Innovations theory to investigate some of the reasons why. A multi-question survey, the PI-created, Pharmacogenomic Adoption Instrument (PAI) ©, was developed to assess the knowledge, attitudes and experience concerning pharmacogenetic technology in a spectrum …

Functional Analysis Of The Molluscum Contagiosum Virus Mc160 Death Effector Domain-Containing Protein Rxdl Motif, Sarah Weber

Seton Hall University Dissertations and Theses (ETDs)

The Molluscum contagiosum virus (MCV) is a member of the Poxviridae family that causes benign skin lesions. MCV lesions persist on average for 8-12 months in otherwise healthy individuals. MCV lesions are characterized by reduced inflammation. The persistence and reduction of inflammation at the site of MCV lesions have been attributed to MCV immune evasion genes. MCV encodes two death effector domain (DED) containing proteins, MC159 and MC160. DEDs are found in cellular proteins such as FADD and procaspase-8. These cellular proteins are involved in several innate immune responses such as apoptosis and activation of interferon (IFN). Presumably, MC159 and …

Submonomer Synthesis And Structure-Activity Relationship Studies Of Azapeptide Inhibitors Of The Insulin Receptor Tyrosine Kinase, Lathamol A. Kurian

Seton Hall University Dissertations and Theses (ETDs)

Azapeptides are a class of peptide mimics (peptidomimetics), which have served as valuable tools for the development of peptide based therapeutic agents. The therapeutic promise of azapeptides has been correlated to its primary sequence modification which translates into bio-active secondary structures that improves the pharmacological properties of the native peptide sequence. More specifically, azapeptides contain a semicarbazide within the peptide backbone which restricts the peptide bond torsion angles (φ, ψ) into pre-organized b-turn secondary structures. Thus, azapeptides have been shown to stabilize bio-active b-turn secondary structures responsible for high affinity and selective binding to a target …

Effects Of Dfo-Induced Hypoxia On Key Signaling Mediators, Jennifer Candelora

Seton Hall University Dissertations and Theses (ETDs)

While diseases such as cancer and diabetes, or surgery and traumatic injury can cause hypoxia through a decrease in blood circulation to bodily regions or decrease cardiac output they can also associate with hypoxia-induced pain. Clinically, opioids, such as morphine, are used to modulate pain. The mu-opioid receptors (MORs) are one of three main types of opioid receptors and are key mediators in morphine-induced analgesia. Therefore, in this study, the effect of hypoxia on MOR gene expression was examined using human neuronal cells treated with DFO to create a hypoxic-mimic condition. We found that MOR expression was shown to decrease …

The Use Of Natural Products As Potential Anti-Pseudomonas Agents, Margaret B. Bell

Seton Hall University Dissertations and Theses (ETDs)

Pseudomonas is a genus of gram-negative gammaproteobacteria with a large range of diversity. Because of its ability to grow at low temperature, Pseudomonas is a cause of food spoilage. This bacterium is also a very common nosocomial infection of hospital patients. In this study, we investigated the effects of different natural products on Pseudomonas. The products included a polysaccharide, two flavonoids tangeretin and nobiletin and their derivatives, 5’OH-tangeretin and 5’OH-nobiletin, black tea polyphenol – theaflavins (TFs), as well as an herb named Fallopia multiflora (Chinese Knotweed). P. fluorescens and P. aeruginosa were used as model organisms. Antimicrobial effects were …

The Experience Of Having Primary Caregiving Responsibilities For An Adult Sibling With Down Syndrome, Patricia Sciscione

Seton Hall University Dissertations and Theses (ETDs)

Abstract

Background: The current generation of adults with Down syndrome is living longer and is likely to outlive their parents. Siblings have been identified as the likely future caregivers for adults with Down syndrome, yet little is known about what the experience is like for those who are currently caring for their siblings. It is necessary to gain an understanding of what the service needs are for this population in order to assist sibling caregivers.

Objectives: To explore and describe the experience of being an adult who is partially or fully involved with primary caregiving responsibilities for a sibling with …

Rna Interference Targeting Glucose-Regulated-Protein 78 Induces Hepg2 Cell Apoptosis, Brittany Blackman

Seton Hall University Dissertations and Theses (ETDs)

Cancer is a complex genetic disease that is driven by genetic mutations resulting in chronic, inappropriate cell proliferation. Many current cancer therapies lack specificity towards tumor tissues, ultimately leading to adverse side effects and limited clinical efficacy. Recently, selective cancer cell therapy has examined a well-characterized cell surface marker that is preferentially expressed on tumor cells. The over-expression of an endoplasmic reticulum chaperone protein, 78-kDa glucose-regulated-protein (GRP78), has been observed on the surface of cancer cells, but not on normal tissues. By selectively targeting GRP78 with short-interfering RNA (siRNA), potent GRP78 silencing is anticipated by the RNA interference (RNAi) pathway. …

Localization And Binding Characteristics Of Kaposi's Sarcoma-Associated Herpesvirus Bcl-2 Protein In The Prevention Of Apoptosis, Erin T. St.Angelo

Seton Hall University Dissertations and Theses (ETDs)

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of various diseases, and it encodes a Bcl-2 homolog, KS-Bcl-2. The Bcl-2 family is important in regulating cellular apoptosis. Pro-apoptotic Bcl-2 family members promote apoptosis through mitochondrial pore formation by Bak and Bax, or through BH3 only domain activators and sensitizers. Anti-apoptotic members, such as cellular Bcl-2 prevent apoptosis through interactions with pro-apoptotic proteins, for instance inhibiting pore formation by binding to Bak and/or Bax. Even though, KS-Bcl-2 has been shown to have an anti-apoptotic function like its homolog, it does not bind to either Bak or Bax, and little is known …

Modulation Of Lps-Induced Activation Of Hepatic Map Kinases, Oliver Surriga

Seton Hall University Dissertations and Theses (ETDs)

Lipopolysaccharide (LPS) is a potent inflammagen that has been found to be primarily responsible for many symptoms caused by gram-negative bacterial infections. The LPS-initiated signal transduction pathways involve several terminal kinases, mainly p42/44 mitogen-activated protein kinase (MAPK), p38 MAPK and c-Jun N-terminal kinase (JNK), ultimately leading to increased expression of genes encoding such inflammatory cytokines as interleukin (IL )-1 �. IL-6 and tumor necrosis factors (TNF)-u. In this study, the effects of age on LPS-induced activation of MAPKs in the liver of rats were examined. Results show that the basal level of phosphorylated p42/44 MAPK was increased in postnatal day …

Characterization Of Kaposi's Sarcoma-Associated Herpesvirus Orf11 As A Possible Dutpase, Christina N. Ramirez

Seton Hall University Dissertations and Theses (ETDs)

A dUTPase is a crucial enzyme that hydrolyzes dUTP to dUMP. This reaction prevents the mutagenic or lethal misincorporation of uracil into DNA. For that reason, the enzyme is required for efficient DNA replication. Previous studies have shown that has ORFl l dUTPase-like motifs and thus may be a dUTPase. Generally, gammaherpesviruses contain six characteristic dUTPase motifs. In particular ORFl 1 and contains motifs 1, 2, 4, 6. While the characteristic motifs of gamroaberpesviruses include motifs 1, 2, 3, 4, 5, and 6, the number of dUTPase-like motifs in ORFl 1 's protein sequence is substantial. Thus, ORFl 1 may …

Increasing Serum 25-Hydroxyvitamin D As A Possible Deterrent To The Onset Of Multiple Sclerosis, Nicholas J. Perretti

Seton Hall University Dissertations and Theses (ETDs)

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Characterization Of Migrating Cells From Ventricular Zone (Vz) To Distant Limbic Structures After Multiple Neonatal Seizures, Melissa Corcia

Seton Hall University Dissertations and Theses (ETDs)

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Studies On The Regulation Of Mu Opioid Receptor Mrna Expression In Shsy-5y Human Neuroblastoma Cells, Xin Yu

Seton Hall University Dissertations and Theses (ETDs)

Prolonged exposure to morphine down-regulates mu opioid receptors (MOR) on both undifferentiated and differentiated (retinoic acid or phorbol ester treated) SHSY-5Y cells. However, morphine pretreatment does not alter MOR receptor affinity for morphine. To investigate the molecular basis for MOR regulation after exposure to its selective agonists, we have developed a quantitative competitive reverse transcriptase-polymerase chain reaction (QC-RT PCR) to quantify the expression of MOR in SHSY-SY cells. Differentiation of SHSY-5Y cells with retinoic acid or phorbol ester up regulated MOR mRNA expression by 30 % and 78%, respectively. A 24 hours treatment with morphine (10 µM) down regulated MOR …

Regulation Of Proto-Oncogenes Expression In Developmental Epilepsy, Mahnoush Shafiei

Seton Hall University Dissertations and Theses (ETDs)

Seizures cause selective neuronal cell loss in vulnerable regions such as the hippocampus, cortex, thalamus or substantia nigra (SN) in human or experimental animals. While the HF can propagate seizures, the SN pars reticulata (SNR) regulates the spread ol seizures in an age-dependent fashion, and the pars compacta (SNC) affects extrapyramidal motor control. In mature animals, both structures are wlnerable to seizure-induced damage. In prepubescent rats, seizure susceptibility is reduced and CA 1 region rs primarily affected. The proto-oncogenes, Bcl-2 and Bax, encode specific proteins that inhibit and promote programmed cell death, respectively. In order to determine whether proto-oncogenes are …

Morphine Enhances The Permeability Across Vascular Endothelial Cell Barriers, Jenine Anday

Seton Hall University Dissertations and Theses (ETDs)

Using three types of in vitro endothelial cell barrier models, we investigated the direct effects and mechanisms of morphine on vascular permeability. Our current studies illustrate LPS induces permeability across these VEC barriers, and is significantly enhanced when co-treated with morphine, displayed using the [ 14 CJ-inulin paracellular marker. Incubation with morphine alone induces permeability in a concentration­ depeodent manner, and is not blocked by the addition of naloxone. Morphine enhances the detrimental effects of LPS on cell viability and alone also decreases endothelial cell viability, concentration-dependently, which is also not affected by naloxone, as demonstrated by the trypan blue …

Standardization Of An Immunoassay For The Detection Of Antibodies To B2 Glycoprotein-I, Eric N. Erickson Jr.

Seton Hall University Dissertations and Theses (ETDs)

Antiphospholipid Syndrome (APS) is an evolving autoimmune disease with numerous clinical manifestations. APS occurs in two forms: Primary Antiphospholipid Syndrome (PAPS) and secondarily in association with other autoimmune disorders such as Systemic Lupus Erythematosis (SLE). In the brief period since its discovery as a cofactor for anticardiolipin antibodies, p1-glycoprotein I (�GPI; apolipoprotein H) has been recognized as the autoantigen in the absence of anionic phospholipid when appropriately presented to human autoantibodies. Recent studies suggest that this presentation requires the surface-dependent unmasking of a cryptic epitope. Immunoassays of autoantibodies directed against p1GPI, developed through the application of suitable polymeric matrices, may …