Chemicals and Drugs Commons^™

Bioerodible Calcium Sulfate Bone Grafting Substitutes With Tailored Drug Delivery Capabilities, Bryan R. Orellana

Theses and Dissertations--Biomedical Engineering

Bone regeneration or augmentation is often required prior to or concomitant with implant placement. With the limitations of many existing technologies, a biologically compatible synthetic bone grafting substitute that is osteogenic, bioerodible, and provides spacing-making functionality while acting as a drug delivery vehicle for bioactive molecules could provide an alternative to ‘gold standard’ techniques.

In the first part of this work, calcium sulfate (CS) space-making synthetic bone grafts with uniformly embedded poly(β-amino ester) (PBAE) biodegradable hydrogel particles was developed to allow controlled release of bioactive agents. The embedded gel particles’ influence on the physical and chemical characteristics of CS was …

Quantification Of Factors Governing Drug Release Kinetics From Nanoparticles: A Combined Experimental And Mechanistic Modeling Approach, Kyle Daniel Fugit

Theses and Dissertations--Pharmacy

Advancements in nanoparticle drug delivery of anticancer agents require mathematical models capable of predicting in vivo formulation performance from in vitro characterization studies. Such models must identify and incorporate the physicochemical properties of the therapeutic agent and nanoparticle driving in vivo drug release. This work identifies these factors for two nanoparticle formulations of anticancer agents using an approach which develops mechanistic mathematical models in conjunction with experimental studies.

A non-sink ultrafiltration method was developed to monitor liposomal release kinetics of the anticancer agent topotecan. Mathematical modeling allowed simultaneous determination of drug permeability and interfacial binding to the bilayer from release …

Synthesis And Biological Evaluation Of Novel Resveratrol And Combretastatin A4 Derivatives As Potent Anti-Cancer Agents, Nikhil Reddy Madadi

Theses and Dissertations--Pharmacy

Resveratrol has been reported as a potential anticancer agent but cannot be used as an antitumor drug due to its chemical and metabolic instability. We have designed and synthesized 184 novel compounds related to resveratrol in an attempt to produce more potent and drug-like molecules. We have identified a tetrazole analog of resveratrol, ST-145(a) as a lead anticancer agent from the resveratrol analog series of compounds with a GI₅₀ value of less than 10nM against almost all the human cancer cell lines in the National Cancer Institute’s screening panel.

In a separate study, we tested the hypothesis that the …

Investigating Structure And Protein-Protein Interactions Of Key Post-Type Ii Pks Tailoring Enzymes, Theresa E. Downey

Theses and Dissertations--Pharmacy

Type II polyketide synthase (PKS) produced natural products have proven to be an excellent source of pharmacologically relevant molecules due to their rich biological activities and chemical scaffolds. Type II-PKS manufactured polyketides share similar polycyclic aromatic backbones leaving their diversity to stem from various chemical additions and alterations facilitated by post-PKS tailoring enzymes. Evidence suggests that post-PKS tailoring enzymes form complexes in order to facilitate the highly orchestrated process of biosynthesis. Thus, protein-protein interactions between these enzymes must play crucial roles in their structures and functions. Despite the importance of these interactions little has been done to study them. In …

Attenuating Trigeminal Neuropathic Pain By Repurposing Pioglitazone And D-Cycloserine In The Novel Trigeminal Inflammatory Compression Mouse Model, Danielle N. Lyons

Theses and Dissertations--Physiology

Approximately 22% of the United States population suffers from a chronic orofacial pain condition. One such condition is known as trigeminal neuropathic pain frequently reported as continuous aching and burning pain, often accompanied by intermittent electrical shock-like sensations. Dental procedures or trauma are known causes of peripheral trigeminal nerve injury and inflammation. Patients who have this type of facial pain also suffer from emotional distress. For these reasons, trigeminal neuropathic pain needs to be studied in more detail to improve the understanding of the etiology and maintenance of this condition, as well as to develop effective treatment strategies. The first …

Effects Of Endogenous Cannabinoid Anandamide On Voltage-Dependent Sodium And Calcium Channels In Rat Ventricular Myocytes, Lina T. Al Kury, Oleg I. Voitychuk, Keun-Hang Susan Yang, Faisal T. Thayyullathil, Petro Doroshenkp, Ali M. Ramez, Yaroslav M. Shuba, Sehamuddin Galadari, Frank Christopher Howarth, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

BACKGROUND AND PURPOSE: The endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA) exerts negative inotropic and antiarrhythmic effects in ventricular myocytes.

EXPERIMENTAL APPROACH: Whole-cell patch-clamp technique and radioligand-binding methods were used to analyse the effects of anandamide in rat ventricular myocytes.

KEY RESULTS: In the presence of 1-10 μM AEA, suppression of both Na(+) and L-type Ca(2+) channels was observed. Inhibition of Na(+) channels was voltage and Pertussis toxin (PTX) - independent. Radioligand-binding studies indicated that specific binding of [(3) H] batrachotoxin (BTX) to ventricular muscle membranes was also inhibited significantly by 10 μM metAEA, a non-metabolized AEA analogue, with …

Structure-Functional Prediction And Analysis Of Cancer Mutation Effects In Protein Kinases, Anshuman Dixit, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

A central goal of cancer research is to discover and characterize the functional effects of mutated genes that contribute to tumorigenesis. In this study, we provide a detailed structural classification and analysis of functional dynamics for members of protein kinase families that are known to harbor cancer mutations. We also present a systematic computational analysis that combines sequence and structure-based prediction models to characterize the effect of cancer mutations in protein kinases. We focus on the differential effects of activating point mutations that increase protein kinase activity and kinase-inactivating mutations that decrease activity. Mapping of cancer mutations onto the conformational …

Leukopenia Management In Thymoglobulin Treated Renal Transplant Recipients, Lynsey S. Biondi Md, Michael J. Moritz Md, Janelle Cyprich

Department of Surgery

No abstract provided.

The Effects Of Dihydrobiopterin And Tetrahydrobiopterin On Hydrogen Peroxide And Nitric Oxide Release During Extracorporeal Shockwave Lithotripsy (Eswl), Brittany Deiling

PCOM Biomedical Studies Student Scholarship

ESWL is an effective, non-invasive therapy utilized to fragment stones in the kidney and subsequently be cleared in the urinary tract. Although lithotripsy provides a safer alternative to invasive treatments for removing stones, ESWL may cause vasoconstriction after ESWL treatment, reducing renal blood flow, which can cause kidney damage leading to acute to chronic hypertension clinically. This may be due to kidney vascular endothelial dysfunction, which is characterized as increased oxidative stress and decreased endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) bioavailability. We hypothesized that ESWL would decrease NO and increase hydrogen peroxide (H₂O₂) in …

Amphiphilic Triazolyl Peptides: Synthesis And Evaluation As Nanostructures, Naser Sayeh, Amir Nasrolahi Shirazi, Donghoon Oh, Jiadong Sun, David Rowley, Antara Banerjee, Arpita Yadav, Rakesh Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

A new class of amphiphilic triazolyl peptides was designed and synthesized from peptide-based building blocks containing alkyne and azide functional groups namely linear (W(pG))3, cyclic[W(pG)]3, and Ac-K(N3)R-NH2,where W, R, K, and pG represent tryptophan, arginine, lysine, and propargylglycine residues, respectively. The linear (W(pG))3 and cyclic [W(pG)]3 peptides containing alkyne residues were conjugated with Ac-K(N3)R-NH2 functionalized with azide group through click chemistry in the presence of CuSO4.5H2O, Cu (powder), sodium ascorbate, and N,N-disopropylethylamine in methanol:water to afford amphiphilic triazolyl linear-linear (WG(triazole-KR-NH2))3 and cyclic-linear [WG(triazole-KR-NH2)]3 peptides, respectively. The secondary structures of both peptides were similar to a distorted α-helix as shown by …

Beta-Alanine Suppresses Malignant Breast Epithelial Cell Aggressiveness Through Alterations In Metabolism And Cellular Acidity In Vitro, Roger A. Vaughan, Nicholas P. Gannon, Randi Garcia-Smith, Yamhilette Licon-Munoz, Miguel A. Barberena, Marco Bisoffi, Kristina A. Trujillo

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Background: Deregulated energetics is a property of most cancer cells. This phenomenon, known as the Warburg Effect or aerobic glycolysis, is characterized by increased glucose uptake, lactate export and extracellular acidification, even in the presence of oxygen. beta-alanine is a non-essential amino acid that has previously been shown to be metabolized into carnosine, which functions as an intracellular buffer. Because of this buffering capacity, we investigated the effects of beta-alanine on the metabolic cancerous phenotype.

Methods: Non-malignant MCF-10a and malignant MCF-7 breast epithelial cells were treated with beta-alanine at 100 mM for 24 hours. Aerobic glycolysis was quantified …

Β-Lactam Estrogen Receptor Antagonists And A Dual-Targeting Estrogen Receptor/Tubulin Ligand, Niamh O'Boyle, Jade K. Pollock, Miriam Carr, Andrew Js Knox, Seema M. Nathwani, Shu Wang, Laura Caboni, Daniela M. Zisterer, Mary Meegan

Articles

Twelve novel β-lactams were synthesised and their antiproliferative effects and binding affinity for the predominant isoforms of the estrogen receptor (ER), ERα and ERβ, were determined. β-Lactams 23 and 26 had the strongest binding affinities for ERα (IC₅₀ values: 40 and 8 nM respectively) and ERβ (IC₅₀ values: 19 and 15 nM). β-Lactam 26 was the most potent in antiproliferative assays using MCF-7 breast cancer cells, and further biochemical analysis showed that it caused accumulation of cells in G₂/M phase (mitotic blockade) and depolymerisation of tubulin in MCF-7 cells. Compound 26 also induced apoptosis and downregulation …

Comparison Of Corded And Cordless Handpieces On Forearm Muscle Activity, Procedure Time And Ease Of Use During Simulated Tooth Polishing, Gayle Mccombs, Daniel M. Russell

Dental Hygiene Faculty Publications

Purpose: Dental professionals suffer from a high prevalence of work-related musculoskeletal disorders (MSD). Dental hygienists in particular have a high prevalence of pain in the forearms and hands. The objective of this study was to compare 1 cordless handpiece to 2 corded handpieces during simulated tooth polishing in terms of the muscle loads (recorded as electromyography (EMG) activity), duration of polishing procedure, and dental hygienist opinion about ease of use. Methods: EMG was used to quantify muscle electrical activity of 4 forearm muscles during simulated dental polishing with 2 corded handpieces (HP-A and HP-B) and 1 cordless handpiece (HP-C). A …

Modified Seed Growth Of Iron Oxide Nanoparticles In Benzyl Alcohol: Magnetic Nanoparticles For Radio Frequency Hyperthermia Treatment Of Cancer, Stanley E. Gilliland Iii

Theses and Dissertations

Iron oxide nanoparticles have received sustained interest for biomedical applications as synthetic approaches are continually developed for precise control of nanoparticle properties. This thesis presents an investigation of parameters in the benzyl alcohol synthesis of iron oxide nanoparticles. A modified seed growth method was designed for obtaining optimal nanoparticle properties for magnetic fluid hyperthermia. With a one or two addition process, iron oxide nanoparticles were produced with crystallite sizes ranging from 5-20 nm using only benzyl alcohol and iron precursor. The effects of reaction environment, temperature, concentration, and modified seed growth parameters were investigated to obtain precise control over properties …

Medication Noncompliance In Patients Over The Age Of 65: Risk Factors, Problems, And Potential Solutions, Rachel N. Cook

Honors Program Theses

Medication noncompliance is linked with a complex medication regimen, poor drug knowledge, physical limitations, psychosocial characteristics, and poor communication. As important as this problem is to patients’ health especially those over the age of 65, there really is no solution to this problem or even steps to a solution. After interviewing eight care providers, I have come up with a few steps to begin solving this problem. These steps include a medication dispenser, communication between care providers, and education provided to patients by all care providers. In the end, there is no solution that will solve every case of medication …

Effect Of Chronic Angiotensin Ii Infusion On Plasma Tnfalpha And Il 6 Levels In Adiponectin Deficient Mice, Alexis O'Brien, Minnette Smith, Jaya Pamidimukkala

College of Osteopathic Medicine (TUN) Publications and Research

Chronic low grade inflammation plays an integral part in the development of many types of cardiovascular diseases. Adipose tissue is a well known source of many proinflammatory mediators. Adiponectin (APN) is one of the few proteins secreted by the adipose tissue that is known to have anti-inflammatory properties. Our research goal is to understand if APN deficiency contributes to a proinflammatory milieu especially when provided with an appropriate stimulus. Angiotensin II (ANGII) is a well known prohypertensive agent. Recently, ANGII has emerged as a growth factor and stimulator of proinflammatory cytokine expression in cardiovascular & renal tissue. The present study …

A Potential Mechanism For Extracellular Matrix Induction Of Breast Cancer Cell Normality, Robert D. Bruno, Gilbert H. Smith

School of Medical Diagnostics & Translational Sciences Publications

Extracellular matrix proteins from embryonic mesenchyme have a normalizing effect on cancer cells in vitro and slow tumor growth in vivo. This concept is suggestive of a new method for controlling the growth and spread of existing cancer cells in situ and indicates the possibility that extracellular proteins and/or embryonic mesenchymal fibroblasts may represent a fertile subject for study of new anti-cancer treatments.

Hydropathic Interactions And Protein Structure: Utilizing The Hint Force Field In Structure Prediction And Protein‐Protein Docking., Mostafa H. Ahmed

Theses and Dissertations

Protein structure predication is a field of computational molecular modeling with an enormous potential for improvement. Side-chain geometry prediction is a critical component of this process that is crucial for computational protein structure predication as well as crystallographers in refining experimentally determined protein crystal structures. The cornerstone of side-chain geometry prediction are side-chain rotamer libraries, usually obtained through exhaustive statistical analysis of existing protein structures. Little is known, however, about the driving forces leading to the preference or suitability of one rotamer over another. Construction of 3D hydropathic interaction maps for nearly 30,000 tyrosines extracted from the PDB reveals their …

Vibrational Spectroscopy: Disease Diagnostics And Beyond, Hugh Byrne, Kamila Ostrowska, Haq Nawaz, Jennifer Dorney, Aidan Meade, Franck Bonnier, Fiona Lyng

Books/Book Chapters

Summary

This chapter outlines some developments in the applications of vibrational spectroscopy for disease diagnostics and demonstrates how the applications of the spectroscopic techniques can be extended to the analysis and evaluation of disease aetiology and the mechanisms of interaction and the cellular and subcellular responses to, for example chemotherapeutic agents and nanoparticles. The primary emphasis is on Raman spectroscopy, although some examples are based on infrared absorption spectroscopy. The studies presented are chosen to illustrate how a range of multivariate analytical techniques can be employed to maximize the potential benefits of the complex spectral information obtained from tissue or …

Identification Of Plasma Lipid Biomarkers In Alzheimer's Disease, Rhona Creegan

Theses: Doctorates and Masters

Alzheimer’s disease (AD), the commonest form of dementia, is a chronic, progressive neurodegenerative disease which manifests clinically as a slow global decline in cognitive function, including deterioration of memory, reasoning, abstraction, language and emotional stability, culminating in a patient with end-stage disease, totally dependent on custodial care. With an ageing population, there is predicted to be a marked increase in the number of people diagnosed with AD in the coming decades, making this a significant challenge to socio-economic policy and aged care. Currently there is no cure for AD and while current therapies may temporarily ameliorate symptoms, death usually occurs …

The Hormones Of The Placenta, Shaya Oratz

The Science Journal of the Lander College of Arts and Sciences

The human pregnancy begins with fertilization and implantation. As the embryo evolves and develops within the uterus of the mother, the placenta is formed. The placenta is a transient organ that develops to meet and accommodate specific needs during pregnancy. Its two major functions are the exchange of nutrients and gases between the mother and fetus and its role as an endocrine unit. Through the production and release of many hormones the placenta works to regulate the many necessary physiological changes in the mother in order to maintain the pregnancy, meet the needs of the developing fetus and prepare the …

The Effect Of Maté On Enzymes Involved In The Recovery From Oxidative Stress, Amina Sadik, Theodore Chang

College of Osteopathic Medicine (TUN) Publications and Research

In comparing the effect of Maté to that of green tea, it has been shown that Maté has higher anti-oxidative properties. We have shown that the extract of Yerba Maté, paraguariensis, leaves does indeed have strong anti-oxidative properties through the evaluation of its scavenging activity and its ability of assist cardiomyocytes in their recovery from induced oxidative stress using both spectroscopy, a colorimetric assay and flow cytometry. In order to elucidate the mechanism behind this action, we quantified the enzymes known to be expressed naturally by cells under oxidative stress such as glutathione peroxidase, superoxide dismutase, and catalase. These enzymes …

Perspectives On: Cyclic Nucleotide Microdomains And Signaling Specificity, Jeffrey W. Karpen

Touro College of Osteopathic Medicine (Middletown) Publications and Research

The author provides an introduction to a special issue on cyclic nucleotides concerning four areas in cAMP compartmentation.

Cardiolipin Prevents Membrane Translocation And Permeabilization By Daptomycin, Tianhua Zhang, Jawad K. Muraih, Nasim Tishbi, Jennifer Herskowitz, Rachel L. Victor, Jared Silverman, Stephanie Uwumarenogie, Scott D. Taylor, Michael Palmer, Evan Mintzer

Lander College of Arts and Sciences Publications and Research

Daptomycin is an acidic lipopeptide antibiotic that, in the presence of calcium, forms oligomeric pores on membranes containing phosphatidylglycerol. It is clinically used against various Gram-positive bacteria such as Staphylococcus aureus and Enterococcusspecies. Genetic studies have indicated that an increased content of cardiolipin in the bacterial membrane may contribute to bacterial resistance against the drug. Here, we used a liposome model to demonstrate that cardiolipin directly inhibits membrane permeabilization by daptomycin. When cardiolipin is added at molar fractions of 10 or 20% to membranes containing phosphatidylglycerol, daptomycin no longer forms pores or translocates to the inner membrane leaflet. Under …

Synthesis And Evaluation Of C-Src Kinase Inhibitory Activity Of Pyridin-2(1h)-One Derivatives, Karam Chand, Suchita Prasad, Rakesh Tiwari, Amir Nasrolahi Shirazi, Sumit Kumar, Keykavous Parang, Sunil K. Sharma

Pharmacy Faculty Articles and Research

Src kinase, a prototype member of the Src family of kinases (SFKs), is over-expressed in various human tumors, and has become a target for anticancer drug design. In this perspective, a series of eighteen 2-pyridone derivatives were synthesized and evaluated for their c-Src kinase inhibitory activity. Among them, eight compounds exhibited c-Src kinase inhibitory activity with IC50 value of less than 25 mu M. Compound 1-[2-(dimethylamino)ethyl]-5-(2-hydroxy-4-methoxybenzoyl)pyridin-2(1H)-one (36) exhibited the highest c-Src kinase inhibition with an IC50 value of 12.5 mu M. Furthermore, the kinase inhibitory activity of compound 36 was studied against EGFR, MAPK and PDK, however no significant activity …