Chemicals and Drugs Commons^™

Aberrant Proliferation In Cxcr7+ Endothelial Cells Via Degradation Of The Retinoblastoma Protein, Jennifer Totonchy, Jessica M. Osborn, Sara Botto, Lisa Clepper, Ashlee V. Moses

Pharmacy Faculty Articles and Research

Angiogenesis is a critical factor in the growth and dissemination of solid tumors. Indeed, tumor vasculature is abnormal and contributes to the development and spread of malignancies by creating a hostile microenvironment. The alternative SDF-1/CXCL12 receptor, CXCR7, is frequently and specifically expressed in tumor-associated vessels. In this study, we examine the role of endothelium-expressed CXCR7 in tumor vascular dysfunction by specifically examining the contribution of CXCR7 to endothelial cell (EC) proliferation. We demonstrate that CXCR7 expression is sufficient to drive post-confluent growth in EC cultures. Further, we provide a novel mechanism for CXCR7-mediated proliferation via proteasomal degradation of the tumor …

Self-Assembled Surfactant Cyclic Peptide Nanostructures As Stabilizing Agents, Dindyal Mandal, Rakesh Tiwari, Amir Nasrolahi Shirazi, Donghoon Oh, Guofeng Ye, Antara Banerjee, Arpita Yadav, Keykavous Parang

Pharmacy Faculty Articles and Research

A number of cyclic peptides including [FR](4), [FK](4), [WK](5), [CR](4), [AK](4), and [WR](n) (n = 3-5) containing L-amino acids were produced using solid-phase peptide synthesis. We hypothesized that an optimal balance of hydrophobicity and charge could generate self-assembled nanostructures in aqueous solution by intramolecular and/or intermolecular interactions. Among all the designed peptides, [WR](n) (n = 3-5) generated self-assembled vesicle-like nanostructures at room temperature as shown by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and/or dynamic light scattering (DLS). This class of peptides represents the first report of surfactant-like cyclic peptides that self-assemble into nanostructures. A plausible mechanistic insight into …

Development Of Proteomic Characterization And Speciation Techniques Utilizing Tryptic Peptides With Maldi-Tof Ms And Lc-Esi Ms-Ms, Jennifer Marie Kooken

Theses and Dissertations

The characterization of microbes which can be opportunists and pathogens (e.g., methicillin resistant Staphylococcus aureus (MRSA)) is important in understanding and potentially treating diseases caused by various bacterial species. Common genera found in the human skin micro-biome include Micrococcus and Staphylococcus, but there only a limited number of tests to differentiate these genera and/or species. My research reflects methods development from distinguishing one closely related genera from another and then expanded to species identification. Tryptic peptides were analyzed by MALDI TOF MS and the mass profiles compared with those of a reference strain in both genus and species identification. Aconitate …

The Anti-Angiogenic Effects Of Sparstolonin B, Henry Rhodes Bateman

Theses and Dissertations

Sparstolonin B (SsnB) is a novel bioreactive compound isolated from Sparganium stoloniferum, an herb historically used in Traditional Chinese Medicine as an anti-tumor agent. SsnB has demonstrated anti-inflammatory properties, inhibiting Toll-like receptor mediated inflammation in isolated macrophages and in mice. Angiogenesis, the process of new capillary formation from existing blood vessels, is dysregulated in many pathological disorders, including atherosclerosis, diabetic retinopathy, and tumor growth. The goal of the project was to investigate the anti-angiogenic effects of SsnB.

The first part of the project utilized in vitro functional assays to study how SsnB affected endothelial cells. SsnB inhibited endothelial cell tube …

Impact Of Physical Activity In The Prevention Of Colorectal Cancer, Sarah Ashley Barnes

Theses and Dissertations

This review evaluates the current understanding of research on the impact of physical activity in the prevention of colorectal cancer. Current biological mechanisms implicated in physical activity and colorectal cancer risk reduction are blood glucose regulation, insulin sensitivity, leptin and adiponectin profiles, inflammation as well as secreted protein acidic and rich in cysteine (SPARC), an exercise induced myokine. Recent literature indicates that 30-60 minutes of moderate to vigorous activity a day is effective against colorectal cancer development, and there is convincing evidence of aerobic exercise as differently beneficial in recruiting mechanisms identified as preventative against colorectal cancer. This article provides …

Resveratrol Attenuates The Development Of Trans-Aortic Constriction (Tac) Induced Heart Failure In Mice, Prakash Kumar Gupta

Theses and Dissertations

Heart failure (HF) still remains the leading cause of morbidity and mortality and imposes severe global affliction and enormous cost on the healthcare system. Although current pharmacological therapies have shown to slow down the progression of HF, but seems to have reached their limits in improving overall patient prognosis. Thus, an immediate call for novel alternate therapies are needed which act independently as well as in conjunction with current treatment modality. Studies were performed in the well-established transverse aortic constriction (TAC) model of chronic pressure overload (PO) in mice. In the first series of studies, Male C57BL6 mice (26-28 g) …

Mass Spectrometry And Tandem Mass Spectrometry Characterization Of Protein Patterns, Protein Markers And Whole Proteomes For Pathogenic Bacteria, Jennifer Intelicato-Young

Theses and Dissertations

There have been many recent reviews published on MALDI-TOF MS (matrix assisted laser desorption/ionization time-of-flight) MS (mass spectrometry) for identification of bacteria particularly with relevance to clinical microbiology. MALDI-TOF MS is now a mature technique for bacterial identification with great promise. The purpose of this review is to put into perspective MALDI-TOF MS and other widely used mass spectrometry methods for characterization of proteins. MALDI-TOF MS is used for rapid determination of a mass pattern of proteins for bacterial characterization; these proteins

are generally not identified. Alternatively, after gel separation, MALDI TOF-TOF MSMS (tandem mass spectrometry) or on-line LC-ESI MS-MS …

Effects Of Endothelial Progenitor Cell-Derived Microvesicles On Hypoxia/Reoxygenation-Induced Endothelial Dysfunction And Apoptosis, Jinju Wang, Shuzhen Chen, Xioatang Ma, Chuanfang Cheng, Xiang Xiao, Ji Chen, Shiming Liu, Bin Zhao, Yanfang Chen

Pharmacology and Toxicology Faculty Publications

Oxidative stress-induced endothelial dysfunction plays a key role in ischemia/reperfusion injury. Recent evidence indicates that endothelial progenitor cell-derived microvesicles (EPC-MVs) can promote angiogenesis of endothelial cells (ECs). Here, we investigated the potential effects of EPC-MVs on hypoxia/reoxygenation (H/R) injury in human brain microvascular ECs (hb-ECs). MVs were prepared from EPCs cultured in a serum deprivation (SD) medium (starving stress, sEPC-MVs) or SD medium containing tumor necrosis factor-α (TNFα) (apoptotic stress, aEPC-MVs). H/R injury model of hb-ECs was produced by 6 hr hypoxia (1% O₂) and 24 hr reoxygenation. The H/R hb-ECs were co-cultured with EPC-MVs. Results showed that …

Can Marijuana Be Harmful When Used Prenatally Or During Adolescence?, Penninah Dean

The Science Journal of the Lander College of Arts and Sciences

Marijuana is a popular recreational drug with a strong following campaigning to legalize it for both medicinal and recreational use. This paper serves to illustrate the harmful effects of marijuana use as it pertains to prenatal, adolescent and adult use. By understanding the methods of absorption and mechanism of interaction in the body, we can see a correlation between the effects of marijuana and its toxicity. Through extensive research of case studies on marijuana use we were able to determine marijuana’s harmful effects physically, developmentally and cognitively. Through these methods of research, it can be concluded that marijuana has detrimental …

The Carcinogenic Effects Of Aspartame, Devora Sara Gelbfish

The Science Journal of the Lander College of Arts and Sciences

Aspartame, one of the most common artificial sweeteners, is used as a food additive worldwide. Because of early experimentation with rats linking aspartame to higher risk of cancer, there is much concern regarding the safety of aspartame. However, analytical review and numerous subsequent studies have disproven previous experimentation and reaffirmed that aspartame consumption in humans does not increase the risk of cancers. At the current time there is no credible evidence to support the idea that aspartame is carcinogenic. The evidence confirms that at current levels of consumption aspartame is a safe alternative to sucrose.

Role Of Microrna-155 In A Mouse Model Of Colon Cancer., Claire Mitchell Midyette

Theses and Dissertations

Colorectal cancer remains the third most common malignancy and the fourth most common cause of cancer mortality worldwide. Dysregulated miRNA levels are associated with several types of malignancies and may serve as important biomarkers and/or therapeutic targets in colorectal cancer. We examined the role of miRNA-155 on tumorigenesis and associated symptoms using a well-characterized mouse model of colorectal cancer. C57BL/6 wild-type mice and miRNA-155-/- mice (n=7-13 group) were given a single injection of AOM (10mg/Kg) followed by 3 cycles of DSS (2% in the water for 1 week followed by 2 weeks of plain water). A C57BL/6 wild-type group that …

Avoidance Disruptive Effect Of Clozapine And Olanzapine Is Potentiated By Increasing The Test Trials: Further Test Of The Motivational Salience Hypothesis, Min Feng, Nan Sui, Ming Li

Department of Psychology: Faculty Publications

Antipsychotic drugs suppress animals’ ability to avoid an aversive stimulus in the conditioned avoidance response model (CAR). This behavioral effect is thought to reflect antipsychotic activity and is suggested to be mediated by a drug’s action in attenuating the motivational salience of a conditioned stimulus (CS). In the present study, we tested whether atypical antipsychotic drugs clozapine and olanzapine act through this behavioral mechanism by manipulating the number of avoidance test trials. We reasoned that more CS trials in the present of clozapine or olanzapine would afford the drug more opportunities to decrease the motivational salience of the CS, thus …

Novel Therapy For Nicotine Addiction In Alcohol Dependent Rats, Bethany Ann Stennett

UNF Graduate Theses and Dissertations

The co-dependence of nicotine and alcohol addiction occurs at high rates, complicates treatment, and is often associated with significant morbidity and mortality. Treatment options of alcohol and tobacco co-dependence are limited. Currently, there are drugs available for nicotine dependence or alcohol dependence. However, there are no therapeutic drugs available on the market for the co-dependence of nicotine and alcohol. Therefore, and important opportunity of new therapeutic options and drug development has presented itself. NT69L, a non-selective neurotensin (NT) agonist, provides a potential novel therapy for nicotine addiction in alcoholics by interacting with the common neurotransmitter circuits supporting the rewarding process …

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 …

Synthesis And Stability Studies Of Prodrugs And Codrugs Of Naltrexone And 6-Β-Naltrexol, Joshua A. Eldridge

Theses and Dissertations--Pharmacy

The present study was divided between two different drug delivery goals, each involving naltrexone (NTX) or its active metabolite, 6-β-naltrexol (NTXOL). First, amino acid esters of NTX and NTXOL were prepared in order to test their candidacy for microneedle-enhanced transdermal delivery. Second, a 3-O-(-)-cytisine-naltrexone (CYT-NTX) codrug was prepared for screening as a potential oral delivery form of NTX and (-)-cytisine (CYT). The amino acid prodrugs were intended for the treatment of alcohol abuse, while the codrug was designed as a single agent for the treatment of alcoholism and tobacco-dependency co-morbidities. One hypothesis of this work was that prodrugs …

Biosynthetic Pathway Of The Aminoribosyl Component Of Lipopeptidyl Nucleoside Antibiotics, Xiuling Chi

Theses and Dissertations--Pharmacy

Several lipopeptidyl nucleoside antibiotics that inhibit bacterial translocase I (MraY) involved in peptidoglycan cell wall biosynthesis contain an aminoribosyl moiety, an unusual sugar appendage in natural products. A-90289 and muraminomicin are the two representative antibiotics that belong to this family. Bioinformatic analysis of the biosynthetic A-90289 gene clusters revealed that five enzymes are likely involved in the assembly and attachment of the aminoribosyl unit. These enzymes of A-90289 are functionally assigned by in vitro characterization. The results reveal a unique ribosylation pathway that highlighted by uridine-5′-monophosphate as the source of the sugar, a phosphorylase strategy to generate a sugar-1-phosphate, and …

Regulation Of Alpha Synuclein Following Chronic Methamphetamine Administration In Guinea Pigs: Correlation With Memory And Synaptic Plasticity, Adnouse Blanc

PCOM Biomedical Studies Student Scholarship

Methamphetamine (METH) is a highly addictive drug of abuse that has a severe impact on neuronal changes in the brain including modulations of plasticity, cognitive dysfunction, as well as memory impairment. These changes can be seen as modifications in the expression of biochemical markers associated with synaptic plasticity. One such marker associated with memory impairment is alpha synuclein (α-syn). Alteration of α-syn expression has been linked to memory impairment in patients with Alzheimer’s disease (AD) and Parkinson’s disease (PD). Here we assess the effect of chronic METH treatment in correlation to cognitive functions.

Twenty-nine guinea pigs (male, 150-250 g) were …

Novel Cis-Restricted Β-Lactam Combretastatin A-4 Analogues Display Anti-Vascular And Anti-Metastatic Properties In Vitro, Seema M. Nathwani, Lisa M. Greene, Linda Hughes, Miriam Carr, Niamh O'Boyle, Susan Mcdonnell, Mary J. Meegan, Daniela M. Zisterer

Articles

No abstract provided.

Stability Of Extemporaneously Prepared Lansoprazole Suspension At Two Temperatures, Jordan T. Morrison, Ralph A. Lugo, Jim C. Thigpen, Stacy D. Brown

ETSU Faculty Works

OBJECTIVE The purpose of this study was to examine the stability of a generic lansoprazole product in a 3 mg/mL sodium bicarbonate suspension under room temperature and refrigerated conditions. METHODS Lansoprazole suspensions (3 mg/mL) were prepared in triplicate using an 8.4% sodium bicarbonate vehicle for each storage condition (room temperature and refrigerated). During 1 month, samples from each replicate were periodically removed and analyzed for lansoprazole concentration by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Each sample was spiked with 10 mg/L omeprazole to serve as the internal standard. A positive electrospray LC-MS/MS method was validated over the calibration range of 5 …

Does The Addition Of Muramyl Tripeptide To Chemotherapy Improve Overall Survival For Patients With Osteosarcoma?, Jennifer Jones

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not “Does the addition of muramyl tripeptide to chemotherapy improve overall survival for patients with osteosarcoma?”

STUDY DESIGN: Review of three English language primary randomized controlled trials published between 2005 and 2009.

DATA SOURCES: Randomized controlled trials evaluating the addition of muramyl tripeptide (MTP) to chemotherapy for patients with osteosarcoma were found using Medline/PubMed databases.

OUTCOMES MEASURED: Event-free survival (EFS) and overall survival were the outcome measures used to determine the effectiveness of the additional chemotherapy treatment in osteosarcoma patients. EFS was defined as …