Pharmacology, Toxicology and Environmental Health Commons^™

No Waste: Nyc, Minda Smiley

Capstones

I produced three video pieces about people who are living zero-waste lifestyles or using zero-waste practices in their businesses. I also wrote a narrative piece about my experience living zero-waste for one week.

Biological And Physiological Condition Of Juvenile California Halibut (Paralichthys Californicus) Exposed To A Contamination Gradient In Mission Bay, Ca, Kevin Stolzenbach

Theses

Contaminated sediments in marine environments have been shown to be good indicators of ecological risk and a means to assess anthropogenic impacts on marine habitats and the animals that inhabit them (Long et al. 1995, Rattner 2009). Estuarine sediments are especially complex media with regard to physical, chemical, and biological characteristics that trap, store, modify and sometimes release contaminants to the biota (Long et al. 1995). Especially vulnerable are animals that are in constant contact with the sediments, such as flatfishes that partially bury themselves for camouflage (Costa et al. 2011). Impacts can be assessed in a number of ways, …

Cd151-Α3Β1 Integrin Complexes Suppress Ovarian Tumor Growth By Repressing Slug-Mediated Emt And Canonical Wnt Signaling, Lauren A. Baldwin, John T. Hoff, Jason Lefringhouse, Michael Zhang, Changhe Jia, Zeyi Liu, Sonia Erfani, Hongyan Jin, Mei Xu, Qing-Bai She, John R. Van Nagell Jr., Chi Wang, Li Chen, Rina Plattner, David M. Kaetzel, Jia Luo, Michael Lu, Dava West, Chunming Liu, Fred R. Ueland, Ronny Drapkin, Binhua P. Zhou, Xiuwei H. Yang

Pharmacology and Nutritional Sciences Faculty Publications

Human ovarian cancer is diagnosed in the late, metastatic stages but the underlying mechanisms remain poorly understood. We report a surprising functional link between CD151-α3β1 integrin complexes and the malignancy of serous-type ovarian cancer. Analyses of clinical specimens indicate that CD151 expression is significantly reduced or diminished in 90% of metastatic lesions, while it remains detectable in 58% of primary tumors. These observations suggest a putative tumor-suppressing role of CD151 in ovarian cancer. Indeed, our analyses show that knocking down CD151 or α3 integrin enhances tumor cell proliferation, growth and ascites production in nude mice. These changes are accompanied by …

Impacts Of Land-Cover Change And High Rainfall On Soil Erosion Among Three Farms In Cerro Punta, Chiriquí, Panamá., Madeline Happ

Independent Study Project (ISP) Collection

Soil erosion is a key source leading to the depletion of Earth’s natural resources. Beginning with deforestation, soils are stripped of their rich vegetation cover, leaving them vulnerable to wind, water, and sometimes total exhaustion. One of the major causes of deforestation, if not the primary cause, is for agricultural purposes. Extensive agricultural fields, steep slopes, and heavy rains characterize the highlands of Chiriquí; thus, the land displays potential for severe loss of soil. This paper illustrates and discusses the extent of soil erosion in Cerro Punta, Chiriquí, specifically considering the steep terrains and very wet environment that impact the …

A Quantitative Analysis Of The Value-Enhancing Effects Of Nicotine, Bupropion, And Varenicline In Male And Female Rats, Scott Barrett

Department of Psychology: Dissertations, Theses, and Student Research

Smoking and tobacco dependence are serious health concerns in the United States and globally. Reward via the pharmacological effects of nicotine are believed to be the principal motivating factor that drive tobacco dependence. Research reveals differences in sensitivity between males and females to the motivational effects of nicotine in tobacco use. Enhancement of reinforcement value of non-nicotine rewards contributes to overall nicotine reward. Similar value-enhancing effects have been observed by the two most commonly prescribed smoking cessation aids, bupropion and varenicline. The present dissertation investigated the value-enhancing effects of nicotine, bupropion and varenicline in both male and female rats using …

Interactive Effects Of Climate Change With Nutrients, Mercury, And Freshwater Acidification On Key Taxa In The North Atlantic Landscape Conservation Cooperative Region, Alfred E. Pinkey, Charles T. Driscoll, David C. Evers, Michael J. Hooper, Jeffrey Horan, Jess W. Jones, Rebecca S. Lazarus, Harold G. Marshall, Andrew Milliken, Barnett A. Rattner, John Schmerfold, Donald W. Sparling

Biological Sciences Faculty Publications

The North Atlantic Landscape Conservation Cooperative LCC (NA LCC) is a public-private partnership that provides information to support conservation decisions that may be affected by global climate change (GCC) and other threats. The NA LCC region extends from southeast Virginia to the Canadian Maritime Provinces. Within this region, the US National Climate Assessment documented increases in air temperature, total precipitation, frequency of heavy precipitation events, and rising sea level, and predicted more drastic changes. Here, we synthesize literature on the effects of GCC interacting with selected contaminant, nutrient, and environmental processes to adversely affect natural resources within this region. Using …

Aminoglycoside-Induced Otoneurotoxicity: Analysis Of Inner Hair Cell Synaptic Plasticity Following Drug Exposure, Matthew M. Abernathy

Dissertations

Aminoglycoside antibiotics are powerful drugs for combating bacterial infections, but are limited in use due to their ototoxicity. This class of drug targets the auditory hair cells of the cochlea, causing cell death, which leads to a decline in auditory function. In spite of much research aimed at revealing a mechanism of damage, there are no co-therapies available to diminish the ototoxic liability of aminoglycosides. Existing research does show that there may be a neurodegenerative process that contributes to the observed toxicity. In an effort towards clarifying present understanding of issue, this dissertation project was conducted to characterize the neurodegenerative …

Evaluating The Effects Of Aroclor 1260 In Non-Alcoholic Fatty Liver Disease : The Role Of Xenobiotic Receptors., Banrida Wahlang

Electronic Theses and Dissertations

Polychlorinated biphenyls (PCBs) are persistent environmental toxicants, present in 100% of US adults and dose-dependently associated with nonalcoholic fatty liver disease (NAFLD) in epidemiologic studies. PCBs are predicted to interact with receptors previously implicated in xenobiotic/energy metabolism and NAFLD. These receptors include the aryl hydrocarbon receptor (AhR), pregnane xenobiotic receptor (PXR), constitutive androstane receptor (CAR), peroxisome proliferator-activated receptors (PPARs), liver-X-receptor and farnesoid-X-receptor. This study evaluated the hepatic effects of the PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity. Male C57Bl/6J mice were fed a control or 42% high fat diet (HFD) …

Development And Characterization Of An Autologous Whole Cell Breast Cancer Vaccine, Samantha Leigh Kurtz

Graduate Theses and Dissertations

Approximately 40,000 women will die from breast cancer in the United States in 2014. About 90% of these deaths will be due to metastases, rather than the primary tumor and majority of metastases are due to the recurrence and progression of non-metastatic disease. Current adjuvant treatments, such as chemotherapy and radiation, have severe side effects and may result in overtreatment and drug resistance.

Since greater than 90% of patients are diagnosed between stages I-III and have minimal residual disease after treatment, there is an opportunity to treat patients with an autologous breast cancer vaccine. Autologous vaccines under development have a …

Numerical Simulations Of In Vitro Nanoparticle Toxicity – The Case Of Poly(Amido Amine) Dendrimers., Marcus Maher, Pratap Naha, Sourav Prasanna Mukherjee, Hugh Byrne

Articles

A phenomenological rate equation model is constructed to numerically simulate nanoparticle uptake and subsequent cellular response. Polyamidoamine dendrimers (generations 4-6) are modelled and the temporal evolution of the intracellular cascade of; increased levels of reactive oxygen species, intracellular antioxidant species, caspase activation, mitochondrial membrane potential decay, tumour necrosis factor and interleukin generation is simulated, based on experimental observations.

The dose and generation dependence of several of these response factors are seen to well represent experimental observations at a range of time points. The model indicates that variations between responses of different cell-lines, including murine macrophages, human keratinocytes and colon cells, …

Molecular Characterization Of Hemoglobin Protein In Larvae Of 4th Instar Chironomidae For Evaluating Environmental Quality, Jun Taek Oh

Seton Hall University Dissertations and Theses (ETDs)

Studying environmental quality is a challenging task. It is a complicated exercise since the environment is constantly influenced by numerous variables such as climate change, anthropogenic activities, and unexpected natural disasters. Traditionally, exposure to chemical pollutants depended on chemical and physical analysis of environmental media. Unfortunately, this approach has not taken into consideration bioavailability of the chemical(s) of interest to exposed organisms and/or modification of the chemical (bioactivation/detoxification) by the organism. Benthic macroinvertebrates (BMIs) have been chosen as bioindicators for numerous environmental biomonitoring programs geared towards the assessment of aquatic ecosystems. Biomonitoring requires a more subtle measure – a biomarker …

A Pilot Study On The Use Of Lecture Tools To Enhance The Teaching Of Pharmacokinetics And Pharmacodynamics, Hollie I. Swanson, Michael T. Piascik

Pharmacology and Nutritional Sciences Faculty Publications

Pharmacokinetics and pharmacodynamics are essential topics contained within the medical curriculum and are highly amenable to active-learning approaches. In this pilot study, we incorporated Lecture Tools, a cloud-based audience response system, into a lecture-based graduate course. Lecture Tools was used by both the instructors and the students during peer presentations. Advantages noted by the instructors include the versatility of the questions that can be presented and the ease with which student assessment can be conducted. Student surveys revealed that, overall, the use of Lecture Tools enhanced student attentiveness and engagement and facilitated student participation in questions and answers. Some disadvantages …

Discovery Of Thienoquinolone Derivatives As Selective And Atp Non-Competitive Cdk5/P25 Inhibitors By Structure-Based Virtual Screening, Arindam Chatterjee, Stephen J. Cutler, Robert J. Doerksen, Ikhlas A. Khan, John S. Williamson

Office for Research Publications and Presentations

Calpain mediated cleavage of CDK5 natural precursor p35 causes a stable complex formation of CDK5/p25, which leads to hyperphosphorylation of tau. Thus inhibition of this complex is a viable target for numerous acute and chronic neurodegenerative diseases involving tau protein, including Alzheimer’s disease. Since CDK5 has the highest sequence homology with its mitotic counterpart CDK2, our primary goal was to design selective CDK5/p25 inhibitors targeting neurodegeneration. A novel structure-based virtual screening protocol comprised of e-pharmacophore models and virtual screening workflow was used to identify nine compounds from a commercial database containing 2.84 million compounds. An ATP non-competitive and selective thieno[3,2- …

Utilizing Indicator Of Reduction In Soils Tubes To Affirm A Serpentinitic Hydric Soil On The California Central Coast, Jason Demoss

Natural Resources Management and Environmental Sciences

Wetlands are vital ecosystems that are crucial in maintaining the life of rare and unique soils, plants, and animals. These ecosystems are key players in water storage, water filtration, carbon storage, and harboring unique species. Since the intervention of human development on the Earth’s surface, almost 50% of the Earth’s original wetlands have either been damaged or destroyed. The identification and assessment of both new and old wetlands is crucial in the survival of these precious ecosystems and their conservation. A 3 month-long study was performed to confirm the hydric status of a soil derived from serpentinitic parent material. The …

Parental Factors That Influence Swimming In Children And Adolescents, Jennifer Pharr, Carol C. Irwin, Richard L. Irwin

Environmental & Global Health Faculty Research

Swimming can be an important source of physical activity across the life-span. Researchers have found that parents influence physical activity behaviors of their children. The purpose of this study was to determine what parental factors influenced the number of days that children swam. Survey respondents (n = 1,909) from six cities across the United States were surveyed at local YMCAs. Children were found to swim significantly more if their parents encouraged them to swim, members of the family knew how to swim and swam with them, or their parents were not afraid of the children drowning or afraid of …

Inhalable Constituents Of Thirdhand Tobacco Smoke: Chemical Characterization And Health Impact Considerations, Mohamad Sleiman, Jennifer M. Logue, Wentai Luo, James F. Pankow, Lara A. Gundel, Hugo Destaillats

Chemistry Faculty Publications and Presentations

Tobacco smoke residues lingering in the indoor environment, also termed thirdhand smoke (THS), can be a source of long-term exposure to harmful pollutants. THS composition is affected by chemical transformations and by air–surface partitioning over time scales of minutes to months. This study identified and quantified airborne THS pollutants available for respiratory exposure, identified potential environmental tracers, and estimated health impacts to nonsmokers. In a ventilated 18 m3 laboratory chamber, six cigarettes were machine-smoked, and levels of particulate matter (PM2.5) and 58 volatile organic compounds (VOCs) were monitored during an aging period of 18 h. Results were compared with field …

Consumption Of Low-Moderate Level Arsenic Contaminated Water Does Not Increase Spontaneous Pregnancy Loss: A Case Control Study, Michael S. Bloom, Iulian Neamtiu, Simona Surdu, Cristian Pop, Ioana-Rodica Lupsa, Doru Anastasiu, Edward F. Fitzgerald, Eugen S. Gurzau

Environmental Health Sciences Faculty Scholarship

Previous work suggests an increased risk for spontaneous pregnancy loss linked to high levels of inorganic arsenic (iAs) in drinking water sources (>10 μg/L). However, there has been little focus to date on the impact of low-moderate levels of iAs in drinking water (<10 >μg/L). To address this data gap we conducted a hospital-based case–control study in Timis County, Romania.

Role Of Group Ii Metabotropic Glutamate Receptor Subtype 2 (Mglur2) In Appetitive And Consummatory Aspects Of Ethanol Reinforcement, Kyle Allyson Windisch

Open Access Dissertations

Background: Group II metabotropic glutamate receptors (mGluR2/3) are predominately presynaptically located G_i/o coupled receptors that are highly expressed in the cortex, nucleus accumbens, amygdala, and hippocampus. Previous studies suggest that group II mGluRs are involved in regulating ethanol (EtOH) consumption and seeking following extinction (Backstrom and Hyytia, 2005; Kufahl, et al., 2011). The sipper tube model, which allows for procedural separation of seeking and consumption, was used to further clarify the role of mGluR2/3 in EtOH-seeking and consumption. The non-selective group II mGluR agonist LY379268 (LY37) and selective mGluR2 positive allosteric modulator (PAM) BINA were used to determine the …

Selective Elimination Of Malignant Melanoma Using The Novel Anti-Tumor Agents, Osw-1 And Peitc, Kausar Begam Riaz Ahmed

Dissertations and Theses (Open Access)

Metastatic melanoma is amongst the most refractory of cancers. Drug resistance and lack of therapeutic selectivity are two main challenges to successful melanoma therapy. Herein, we investigated the mechanims of anticancer activity and therapeutic selectivity of two novel agents, 3β, 16β, 17α-trihydroxycholest-5-en-22-one 16-O-[2-O-4-methoxybenzoyl-β-D-xylopyranosyl]- [1→3]-2-O-acetyl-α-l-arabinopyranoside (OSW-1) and β-Phenylethyl Isothiocyanate (PEITC) in melanoma.

OSW-1 inhibited melanoma cell viability at nanomolar concentrations with minimal toxicity to normal melanocytes. Mechanistic studies revealed that OSW-1 suppressed Disialoganglioside 3 Synthase (GD3S) gene expression in melanoma cells, leading to inhibition of gangliosides GD3 and GD2. GD3 is an abundantly expressed melanoma …

Toxicity Of Engineered Nanomaterials And Their Transformation Products Following Wastewater Treatment On A549 Human Lung Epithelial Cells, Yanjun Ma, Subbiah Elankumaran, Linsey C. Marr, Eric P. Vejerano, Amy Pruden

Faculty Publications

Here we characterize the toxicity of environmentally-relevant forms of engineered nanomaterials (ENMs), which can transform during wastewater treatment and persist in aqueous effluents and biosolids. In an aerosol exposure scenario, cytotoxicity and genotoxicity of effluents and biosolids from lab-scale sequencing batch reactors (SBRs) to A549 human lung epithelial cells were examined. The SBRs were dosed with nanoAg, nano zero-valent iron (NZVI), nanoTiO2 and nanoCeO2 at sequentially increasing concentrations from 0.1 to 20 mg/L. Toxicities were compared to outputs from SBRs dosed with ionic/bulk analogs, undosed SBRs, and pristine ENMs. Pristine nanoAg and NZVI showed significant cytotoxicity to A549 cells in …

Treating Cocaine Dependency With Psychopharmacotherapy And Behavioral Therapy, Robyn Liebman

e-Research: A Journal of Undergraduate Work

Cocaine is an addictive drug that affects more than 14 million people globally, according to the United Nations. This paper is a conceptual meta-analysis of numerous studies that tested the effects of psychopharmacological therapy along with behavioral therapy in the treatment of cocaine addiction. It is hypothesized that cocaine dependent individuals treated with a combination of psychopharmacological and behavioral therapies will be less likely to use cocaine. Measurements of cocaine use throughout the experiments were generally assessed by urine screenings. Results indicate that there is more evidence that a combination of psychopharmacological and behavioral therapies will reduce cocaine use. There …

Acid-Base Properties Of The Adsorption Of Synthetic Dyes From Solutions, Rada-Mayya Kostadinova, Gabriela Sikorska, Michelle Naidoo, Abel E. Navarro

Publications and Research

The presence of synthetic dyes is often underestimated in environmental protection. However, it has been demonstrated the impact of colored compounds in ecology and human health. Green tea (GT) and peppermint (PM) tea bag wastes were used as potential adsorbents of dyes from aqueous solutions to evaluate the effect of pH on the adsorption. Basic yellow 57, basic blue 99 and crystal violet were chosen as model dyes due to their widespread use in the industry. Dye solutions at different pH values were placed in contact with the adsorbents in batch experiments at room temperature. Results indicate that crystal violet …

Size Dependent Translocation And Fetal Accumulation Of Gold Nanoparticles From Maternal Blood In The Rat., Manuela Semmler-Behnke, Jens Lipka, Alexander Wenk, Martin Schäffler, Furong Tian, Günter Schmid, Günter Oberdörster, Wolfgang G. Kreyling

Articles

Background

There is evidence that nanoparticles (NP) cross epithelial and endothelial body barriers. We hypothesized that gold (Au) NP, once in the blood circulation of pregnant rats, will cross the placental barrier during pregnancy size-dependently and accumulate in the fetal organism by 1. transcellular transport across the hemochorial placenta, 2. transcellular transport across amniotic membranes 3. transport through ~20 nm wide transtrophoblastic channels in a size dependent manner. The three AuNP sizes used to test this hypothesis are either well below, or of similar size or well above the diameters of the transtrophoblastic channels.

Methods

We intravenously injected monodisperse, negatively …

Biological Activities Of Fusarochromanone: A Potent Anti-Cancer Agent, Elahe Mahdavian, Phillip Palyok, Steven Adelmund, Tara Williams-Hart, Brian D. Furmanski, Yoon-Jee Kim, Ying Gu, Mansoureh Barzegar, Yang Wu, Kaustubh N. Bhinge, Gopi K. Kolluru, Quincy A. Quick, Yong-Yu Liu, Christopher G. Kevil, Brian A. Salvatore, Shile Huang, John L. Clifford

Biology Faculty Research

Background

Fusarochromanone (FC101) is a small molecule fungal metabolite with a host of interesting biological functions, including very potent anti-angiogenic and direct anti-cancer activity.

Results

Herein, we report that FC101 exhibits very potent in-vitro growth inhibitory effects (IC₅₀ ranging from 10nM-2.5 μM) against HaCat (pre-malignant skin), P9-WT (malignant skin), MCF-7 (low malignant breast), MDA-231 (malignant breast), SV-HUC (premalignant bladder), UM-UC14 (malignant bladder), and PC3 (malignant prostate) in a time-course and dose-dependent manner, with the UM-UC14 cells being the most sensitive. FC101 induces apoptosis and an increase in proportion of cells in the sub-G1 phase in both HaCat and P9-WT …

Phytochemical, Antioxidant And Antibacterialpotential Of Elaeagnus Kologa (Schlecht.) Leaf., Zoe Merculieff, Shubharani Ramnath, Seethalakshmi Madhukar Sankoli, Sivaram Venkataramegowda, Ganti S. Murthy, Ruben Michael Ceballos

Biological Sciences Faculty Publications and Presentations

Objective To screen different solvent extracts of Elaeagnus kologa (E. kologa) leaf to determine the phytochemicals, potent antioxidant and antibacterial activity to find out the possible source of applied pharmaceutical formulations. Methods Solvent extracts of leaf material were prepared using the Soxhlet apparatus. A study was performed on antioxidant activity of methanolic extract of leaf by 1-1-diphenyl-2-picrylhydrazyl method. The phenolic and flavonoid content of all the fractions were determined using high performance liquid chromatography. Leaves were also subjected to protein and carbohydrate test. Results The total phenols, flavonoids were found to be high in petroleum ether as compare to other …

Sex-Specific Alterations In Nos Regulation Of Vascular Function In Aorta And Mesenteric Arteries From Spontaneously Hypertensive Rats Compared To Wistar Kyoto Rats, Analia S. Loria, Krystal N. Brinson, Brandon M. Fox, Jennifer C. Sullivan

Pharmacology and Nutritional Sciences Faculty Publications

The present study tested the hypothesis that spontaneously hypertensive rats (SHR) have impaired nitric oxide synthase (NOS)-mediated regulation of vascular function versus Wistar-Kyoto rats (WKY). Aorta and small mesenteric arteries were studied from male and female SHR (M SHR and F SHR) and WKY (M WKY and F WKY). Phenylephrine (PE)-induced vasoconstriction was greater in aorta of M SHR versus all others (P < 0.05); there were neither sex nor strain differences in PE contraction in mesenteric arteries. The NOS inhibitor l-Nitro-Arginine Methyl Ester (l-NAME) increased PE-induced vasoconstriction in all rats, although the increase was the least in male SHR (P < 0.05), revealing a blunted vasoconstrictor buffering capacity of NOS. l-NAME increased sensitivity to PE-induced constriction only in mesenteric arteries of SHR, although, the maximal percent increase in contraction was comparable among groups. ACh-induced relaxation was also less in aorta from M SHR versus all others (P < 0.05). ACh relaxation was comparable among groups in mesenteric arteries, although SHR exhibited a greater NOS component to ACh-induced relaxation than WKY. To gain mechanistic insight into sex and strain differences in vascular function, NOS activity and NOS3 protein expression were measured. Aortic NOS activity was comparable between groups and M SHR had greater NOS3 expression than M WKY. In contrast, although vascular function was largely maintained in mesenteric arteries of SHR, NOS activity was less in SHR versus WKY. In conclusion, M SHR exhibit a decrease in NOS regulation of vascular function compared to F SHR and WKY, although this is not mediated by decreases in NOS activity and/or expression.

Health Risks Caused By Wireless Technologies, Durreeshahwar Zafarahmed, Qurrat-Ul-Ain Zafarahmed

Journal of Undergraduate Research at Minnesota State University, Mankato

There are many health issues related to the use of cellular phones, wireless local area networks, and other devices that emit electromagnetic radiation (EMR). Some of these systems have become a part of our daily lives and many of us are in direct or indirect contact for extended period of times with these devices. However, the general public is unaware of the health risks associated with the use of these devices. Our research covers studies done by individuals as well as organizations on the harmful effects on the health of people from these devices and their claims. We also present …

Post-Transplant High-Dose Cyclophosphamide For The Prevention Of Graft-Versus-Host Disease, Ahmad Samer Al-Homsi, Tara S. Roy, Kelli Cole, Benjamin Feng, Ulrich Duffner

Peer Reviewed Articles

Cyclophosphamide's lack of hematopoietic stem cell toxicity and its unique effects on the immune system have prompted several investigators to explore its potential for the prevention of graft-versus-host disease (GVHD). In haploidentical hematopoietic stem cell transplants, post-transplant cyclophosphamide together with standard prophylaxis reduces the incidence of GVHD to acceptable rates without the need for T cell depletion. In matched related and unrelated donor settings, cyclophosphamide alone has produced encouraging results. In particular, the low incidence of chronic GVHD is noteworthy. Here, we present a review of the current understanding of the mechanism of action of post-transplant cyclophosphamide and summarize the …

Neuroinflammation And Neurologic Deficits In Diabetes Linked To Brain Accumulation Of Amylin, Sarah Srodulski, Savita Sharma, Adam B. Bachstetter, Jennifer M. Brelsfoard, Conrado Pascual, Xinmin Simon Xie, Kathryn E. Saatman, Linda J. Van Eldik, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: We recently found that brain tissue from patients with type-2 diabetes (T2D) and cognitive impairment contains deposits of amylin, an amyloidogenic hormone synthesized and co-secreted with insulin by pancreatic β-cells. Amylin deposition is promoted by chronic hypersecretion of amylin (hyperamylinemia), which is common in humans with obesity or pre-diabetic insulin resistance. Human amylin oligomerizes quickly when oversecreted, which is toxic, induces inflammation in pancreatic islets and contributes to the development of T2D. Here, we tested the hypothesis that accumulation of oligomerized amylin affects brain function.

METHODS: In contrast to amylin from humans, rodent amylin is neither amyloidogenic nor cytotoxic. …

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 …