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B-Type Natriuretic Peptide And C-Reactive Protein In The Prediction Of Atrial Fibrillation Risk: The Charge-Af Consortium Of Community-Based Cohort Studies, Moritz F. Sinner, Emelia J. Benjamin, Alvaro Alonso, David D. McManus 2014 University of Massachusetts Medical School

B-Type Natriuretic Peptide And C-Reactive Protein In The Prediction Of Atrial Fibrillation Risk: The Charge-Af Consortium Of Community-Based Cohort Studies, Moritz F. Sinner, Emelia J. Benjamin, Alvaro Alonso, David D. Mcmanus

Meyers Primary Care Institute Publications and Presentations

AIMS: B-type natriuretic peptide (BNP) and C-reactive protein (CRP) predict atrial fibrillation (AF) risk. However, their risk stratification abilities in the broad community remain uncertain. We sought to improve risk stratification for AF using biomarker information.

METHODS AND RESULTS: We ascertained AF incidence in 18 556 Whites and African Americans from the Atherosclerosis Risk in Communities Study (ARIC, n=10 675), Cardiovascular Health Study (CHS, n = 5043), and Framingham Heart Study (FHS, n = 2838), followed for 5 years (prediction horizon). We added BNP (ARIC/CHS: N-terminal pro-B-type natriuretic peptide; FHS: BNP), CRP, or both to a previously reported AF risk ...


Quantifying The Effect Of A Novel Topical Hyaluronic-Acid Phosphatidylethanolamine Cream On The Epidermis, Caitlin J. Symonette 2014 Western University

Quantifying The Effect Of A Novel Topical Hyaluronic-Acid Phosphatidylethanolamine Cream On The Epidermis, Caitlin J. Symonette

University of Western Ontario - Electronic Thesis and Dissertation Repository

With aging, keratinocytes have diminished proliferative capacity resulting in atrophic skin with reduced barrier function. This investigation evaluates the effect of daily topical applications of a novel high-molecular weight hyaluronan cream (HA-PE) on keratinocyte renewal and epidermal thickness. Unmodified hyaluronan and HA-PE were mixed separately into a vehicle cream. Each topical formulation was applied daily onto the shaved backs of aged female C57BL6 mice. Full-thickness biopsies of treated skin were obtained for analysis of keratinocyte proliferation, keratinocyte differentiation, and local inflammation at days 1, 5, and 10 of cream application. In addition, a cardiac puncture was performed for serum C-reactive ...


Synthesis And Biological Study Of Adenylyl Cyclase Inhibitors, Siyuan Sun, Zhishi Ye, Mingji Dai 2014 Purdue University

Synthesis And Biological Study Of Adenylyl Cyclase Inhibitors, Siyuan Sun, Zhishi Ye, Mingji Dai

The Summer Undergraduate Research Fellowship (SURF) Symposium

Adenylyl cyclases (AC) is a critical family of enzymes which modulates the dynamic cellular level of cAMP, cyclic adenosine monophosphate. The study of cAMP showed that it is indispensable for the signal transduction cascades during many physiological processes, such as immune responses and metabolism which highly relate to cancers. Previous studies of AC inhibitors have been limited due to a lack of isoform-selective small molecule modulators. Selectivity of the molecules is imperative to the activation of only the desired AC inhibitor. The design of the described project was to test the structure activity relationship (SAR) by synthesizing a class of ...


Tissue Engineering: Applications In Developmental Toxicology, Stephanie N. Thiede, Nimisha Bajaj, Kevin Buno, Sherry L. Voytik-Harbin 2014 Purdue University

Tissue Engineering: Applications In Developmental Toxicology, Stephanie N. Thiede, Nimisha Bajaj, Kevin Buno, Sherry L. Voytik-Harbin

The Summer Undergraduate Research Fellowship (SURF) Symposium

In vivo toxicology assays are expensive, low-throughput, and often not predictive of a human response. Three-dimensional in vitro human cell-based tissue systems incorporating cell-cell and cell-matrix interactions have promise to provide high-throughput, physiologically-relevant information on the mechanism of the toxin and a more accurate assessment of the toxicity of a chemical before progression to human trials. Quantification of the disruption of vasculogenesis, the de novo formation of blood vessels from endothelial progenitor cells, can serve as an appropriate indicator of developmental toxicity since vasculogenesis is critical to the early development of the circulatory system. The current routinely used in vitro ...


Treating Cocaine Dependency With Psychopharmacotherapy And Behavioral Therapy, Robyn Liebman 2014 Chapman University

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 ...


Pharmacological And Pre-Clinical Testing Of 5-Nidr As A New Therapeutic Agent Against Brain Cancer, Seol Casey Kim, Anthony Berdis, Jung-Suk Choi 2014 Cleveland State University

Pharmacological And Pre-Clinical Testing Of 5-Nidr As A New Therapeutic Agent Against Brain Cancer, Seol Casey Kim, Anthony Berdis, Jung-Suk Choi

Undergraduate Research Posters 2014

Approximately 4,000 children in the United States are diagnosed annually with a brain tumor. Brain cancers are the deadliest of all pediatric cancers as they have survival rates of less than 20%. Although surgery and radiation therapy are widely used to treat adult patients, chemotherapy is the primary therapeutic option for children. One important chemotherapeutic agent is temozolomide, an alkylating agent that causes cell death by damaging DNA. In this project, we tested the ability of a specific non-natural nucleoside developed in our lab, designated 5-NIdR, to increase the efficacy of temozolomide against brain cancer. Cell-based studies demonstrate that ...


A Feedback Loop Couples Musashi-1 Activity To Omega-9 Fatty Acid Biosynthesis: A Phd Dissertation, Carina C. Clingman 2014 University of Massachusetts Medical School

A Feedback Loop Couples Musashi-1 Activity To Omega-9 Fatty Acid Biosynthesis: A Phd Dissertation, Carina C. Clingman

GSBS Dissertations and Theses

All living creatures change their gene expression program in response to nutrient availability and metabolic demands. Nutrients and metabolites can directly control transcription and activate second-­‐messenger systems. In bacteria, metabolites also affect post-­‐transcriptional regulatory mechanisms, but there are only a few isolated examples of this regulation in eukaryotes. Here, I present evidence that RNA-­‐binding by the stem cell translation regulator Musashi-­‐1 (MSI1) is allosterically inhibited by 18-­‐22 carbon ω-­‐9 monounsaturated fatty acids. The fatty acid binds to the N-­‐terminal RNA Recognition Motif (RRM) and induces a conformational change that prevents RNA association. Musashi ...


Investigating Propargyl-Linked Antifolates In Inhibiting Bacterial And Fungal Dihydrofolate Reductase, Joshua Andrade 2014 University of Connecticut

Investigating Propargyl-Linked Antifolates In Inhibiting Bacterial And Fungal Dihydrofolate Reductase, Joshua Andrade

Honors Scholar Theses

Antimicrobial agents have been invaluable in reducing illness and death associated with bacterial infection. However, over time, bacteria have evolved resistance to all major drug classes as a result of selective pressure. The advancement of new drug compounds is therefore vital. The Anderson-Wright Lab has focused on developing potent and selective inhibitors of dihydrofolate reductase (DHFR), an enzyme key in cell proliferation and survival, in several pathogenic species. The lab has found that a set of compounds, known as propargyl-linked antifolates, are DHFR inhibitors that are both biologically effective and have strong pharmacokinetic properties.

The efficacy of novel propargyl-linked antifolates ...


Synthesis Of Carbohydrate Functionalized Dendrons For Use As Multivalent Scaffold And In Self-Assembled Structures, Namrata Jain 2014 Western University

Synthesis Of Carbohydrate Functionalized Dendrons For Use As Multivalent Scaffold And In Self-Assembled Structures, Namrata Jain

University of Western Ontario - Electronic Thesis and Dissertation Repository

Carbohydrates are implicated in a large number of biological processes ranging from cell-cell interactions to bacterial and viral infection. Lectins are carbohydrate-binding proteins that are generally specific for certain sugars. However, typical carbohydrate–lectin interactions tend to have very low monomeric binding affinities. In many cases, the binding of saccharide ligands by protein receptors can be improved significantly through the attachment of multiple saccharide residues to a common support. Dendronized polymers constitute a class of macromolecules whose nanoscale size, rigidity, and functionality can be controlled with precision by tuning their molecular architecture. It is hypothesized that due to their large ...


Submonomer Synthesis And Structure-Activity Relationship Studies Of Azapeptide Inhibitors Of The Insulin Receptor Tyrosine Kinase, Lathamol A. Kurian 2014 Seton Hall University

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 receptor or ...


Functional Assessment And Potential Therapeutic Role Of Carbon Monoxide Releasing Molecule-­‐3 In A Rodent Model Of Compartment Syndrome, Al Walid Hamam 2014 Western University

Functional Assessment And Potential Therapeutic Role Of Carbon Monoxide Releasing Molecule-­‐3 In A Rodent Model Of Compartment Syndrome, Al Walid Hamam

University of Western Ontario - Electronic Thesis and Dissertation Repository

Compartment syndrome (CS) is a life and limb threatening condition resulting in long term morbidity. Gold standard treatment of CS is surgical fasciotomy. Long-term morbidity is common post fasciotomy. We tested a gait analysis system (CatWalk™) to see if we could detect functional effects of CS in our rodent model. We also investigated the effects of carbon monoxide releasing molecule-3 (CORM-3) on the function of gait in rodents post CS.

The CatWalkTM system was able to detect abnormalities in a rodent’s gait post CS. CORM-3 was also found to alleviate the functional deficits following CS. Multiple dose but not ...


Effect Of Sweeteners On The Renin-Angiotensin System In Rats, Jacob Ball 2014 Minnesota State University, Mankato

Effect Of Sweeteners On The Renin-Angiotensin System In Rats, Jacob Ball

Journal of Undergraduate Research at Minnesota State University, Mankato

Normal abundant dietary sugars such as fructose and sucrose can contribute to hypertension and other health issues. To avoid these health complications, many individuals use artificial sweeteners. An equivalent intake of some artificial sweeteners also can lead to hypertension. However, Stevia, a sweetener that is isolated from a Paraguayan plant, was shown in relevant literature to decrease blood pressure in both rat specimens and humans. The general purpose of this research project was to study the effect of Stevia, saccharin, and sucrose on the expression of two key components of the renin-angiotensin- aldosterone system (RAAS): prorenin receptor (PRR) and angiotensin ...


Cardiovascular Toxicity Of Common Chemotherapy Drugs Used To Treat Breast Cancer: An Overview, Charles A. Bomzer 2014 Aurora Health Care

Cardiovascular Toxicity Of Common Chemotherapy Drugs Used To Treat Breast Cancer: An Overview, Charles A. Bomzer

Journal of Patient-Centered Research and Reviews

Treatment of breast cancer often exposes patients to many different drugs. Some of these drugs have toxic effects involving the cardiovascular system. This review provides an overview of the drugs most commonly used to treat breast cancer and their potential adverse impact on the cardiovascular system.


Production Of Recombinant Human Coagulation Factor Ix By Transgenic Pig, Weijie Xu 2014 University of Nebraska - Lincoln

Production Of Recombinant Human Coagulation Factor Ix By Transgenic Pig, Weijie Xu

Chemical & Biomolecular Engineering Theses, Dissertations, & Student Research

Hemophilia B is the congenital bleeding disorder caused by deficiency in functional coagulation factor IX (FIX) and about 28,000 patients worldwide in 2012. And current treatment is restricted to protein-replacement therapy, which required FIX concentrates for patients’ life-time. Approximately 1 billion units FIX were consumed in 2012. However, still about 70-80% patients, mostly in developing countries, received inadequate or no treatment because of the unavailable and/or unaffordable FIX concentrates. Considering safety reasons, e.g. transmission of blood-borne diseases, the recombinant human FIX (rFIX) is recommended other than the plasma-derived FIX. However, only one rFIX is currently available on ...


Getting To The Root Of Bacterial Hairs: What Is “S”?, Rebecca Gaddis, Samantha O'Conner, Evan Anderson, Terri Camesano, Nancy Burnham 2014 University of Massachusetts Medical School

Getting To The Root Of Bacterial Hairs: What Is “S”?, Rebecca Gaddis, Samantha O'Conner, Evan Anderson, Terri Camesano, Nancy Burnham

UMass Center for Clinical and Translational Science Research Retreat

An atomic force microscope (AFM) was used to measure the steric forces of lipopolysaccharides (LPS) on the biofilm-forming bacteria, Pseudomonas aeruginosa. It is well known that LPS play a vital role in biofilm formation. These forces were characterized with a modified version of the Alexander and de Gennes (AdG) model for polymers, which is a function of equilibrium brush length, L, probe radius, R, temperature, T, separation distance, D, and an indefinite density variable, s. This last parameter was originally distinguished by de Gennes as the root spacing or mesh spacing depending upon the type of polymer adhesion; however since ...


Long-Term Effects Of Use Of Prescription Non-Steroidal Anti-Inflammatory Agents On Symptoms And Disease Progression Among Patients With Radiographically Confirmed Osteoarthritis Of The Knee, Kate L. Lapane, Shibing Yang, Jeffrey B. Driban, Shao-Hsien Liu, Catherine E. Dube, Timothy E. McAlindon, Charles B. Eaton 2014 University of Massachusetts Medical School

Long-Term Effects Of Use Of Prescription Non-Steroidal Anti-Inflammatory Agents On Symptoms And Disease Progression Among Patients With Radiographically Confirmed Osteoarthritis Of The Knee, Kate L. Lapane, Shibing Yang, Jeffrey B. Driban, Shao-Hsien Liu, Catherine E. Dube, Timothy E. Mcalindon, Charles B. Eaton

UMass Center for Clinical and Translational Science Research Retreat

Objective: To estimate the extent to which long-term use of prescription non-steroidal anti-inflammatory agents (NSAIDs) relieve symptoms and delay disease progression among patients with radiographically confirmed osteoarthritis (OA) of the knee.

Methods: Using Osteoarthritis Initiative data, we identified participants with confirmed OA at enrollment and evaluated changes in symptoms measured using the Western Ontario and McMaster Universities Arthritis Index, WOMAC (n=1,846) and joint space width measured using serial x-rays and a customized software tool (n=1,116) over 4 years. Covariates included sociodemographics, OA clinical characteristics, indices of general health status, body mass index, and use of other ...


Targeted Mutagenesis Of A Therapeutic Human Monoclonal Igg1 Antibody Prevents Gelation At High Concentrations, Paul Casaz, Elisabeth N. Boucher, Rachel Wollacott, Sadettin S. Ozturk, William D. Thomas Jr., Yan Wang 2014 University of Massachusetts Medical School

Targeted Mutagenesis Of A Therapeutic Human Monoclonal Igg1 Antibody Prevents Gelation At High Concentrations, Paul Casaz, Elisabeth N. Boucher, Rachel Wollacott, Sadettin S. Ozturk, William D. Thomas Jr., Yan Wang

UMass Center for Clinical and Translational Science Research Retreat

A common challenge encountered during development of high concentration monoclonal antibody formulations is preventing self-association. Depending on the antibody and its formulation, self-association can be seen as aggregation, precipitation, opalescence or phase separation. Here we report on an unusual manifestation of self-association, formation of a semi-solid gel or “gelation”. Therapeutic monoclonal antibody C4 was isolated from human B cells based on its strong potency in neutralizing bacterial toxin in animal models. The purified antibody possessed the unusual property of forming a firm, opaque white gel when it was formulated at concentrations >40 mg/mL and the temperature was <6oC. Gel formation was reversible and was affected by salt concentration or pH, suggesting a charge interaction between IgG monomers. However, formulation optimization could not completely prevent gelation at high concentrations so a protein engineering approach was sought to resolve the problem. A comparison of the heavy and light chain amino acid sequences to consensus germline sequences revealed 16 amino acid sequence differences in the framework regions that could be involved with gelation. Restoring the C4 framework sequence to consensus germline residues by targeted mutagenesis resulted in no gel formation at 50 mg/ml at temperatures as low as 0oC. Additional genetic analysis was used to identify the key residue(s) involved in the gelation. A single substitution in the native antibody, replacing heavy chain glutamate 23 with lysine, was found sufficient to prevent gelation, while a double mutation, replacing heavy chain serine 85 and threonine 87 with arginine, increased the temperature at which gel formation initiated. These results indicate that the temperature dependence of gelation may be related to conformational changes near the charged residues or the regions interact with. Our work provided a molecular strategy that can be applied to improve the solubility of other therapeutic antibodies.


Cranberry Fruit And Leaf Polyphenols Inhibit Staphylococcus Bacterial Biofilms, Catherine C. Neto, Jason MacLean, Biqin Song, Anthony Dovell, Steven Kwasny, Timothy Opperman 2014 University of Massachusetts Medical School

Cranberry Fruit And Leaf Polyphenols Inhibit Staphylococcus Bacterial Biofilms, Catherine C. Neto, Jason Maclean, Biqin Song, Anthony Dovell, Steven Kwasny, Timothy Opperman

UMass Center for Clinical and Translational Science Research Retreat

Cranberry (Vaccinium macrocarpon) is known for urinary tract health benefits associated with reducing the adhesion of E. coli bacteria. This property has been linked to cranberry polyphenols known as proanthocyanidins. Staphylococcus bacteria are a growing public health concern due to development of resistant strains. Identification of agents that inhibit biofilm formation by these bacteria may provide a new route to reduce infection in clinical settings. Fruit and leaves of North American cranberry (Vaccinium macrocarpon) and cranberry juice were fractionated and screened for their ability to prevent biofilm formation by several strains of S. aureus and S. epidermidis bacteria. MALDI-TOF MS ...


Inhibition Of Protein Tyrosine Phosphatase 1b By Polyphenol Natural Products: Relevant To Diabetes Management, Zhiwei Liu, Maolin Guo 2014 University of Massachusetts Medical School

Inhibition Of Protein Tyrosine Phosphatase 1b By Polyphenol Natural Products: Relevant To Diabetes Management, Zhiwei Liu, Maolin Guo

UMass Center for Clinical and Translational Science Research Retreat

Many biologically active polyphenols have been recognized for their beneficial effects in managing diabetes and their complications. However, the mechanisms behind their functions are poorly understood. As protein-tyrosine phosphatase 1B (PTP1B) has been identified as a target for anti-diabetic agents, the potential inhibitory effects of a dozen structurally diverse polyphenol natural products have been investigated. Among these polyphenols, potent inhibitory activities have been identified for 6 of them with IC50 in micromolar range, while the other polyphenols showed very weak inhibition. A structure-activity relationship (SAR) study and molecular ducking results suggest that both a rigid planar 3-ring backbone and appropriate ...


Inhibition Of Colon Cancer By Polyphenols From Whole Cranberry, Catherine Neto, Anne Liberty, Sarah Frade, Anuradha Tata, Tracie Ferreira, Mingyue Song, Xian Wu, Hang Xiao 2014 University of Massachusetts Medical School

Inhibition Of Colon Cancer By Polyphenols From Whole Cranberry, Catherine Neto, Anne Liberty, Sarah Frade, Anuradha Tata, Tracie Ferreira, Mingyue Song, Xian Wu, Hang Xiao

UMass Center for Clinical and Translational Science Research Retreat

The ability of cranberry fruit extracts to inhibit colon carcinogenesis is under investigation using a combination of in vitro and in vivo methods. Compounds isolated from cranberry fruit (Vaccinium macrocarpon) including oligomeric polyphenols known as proanthocyanidins (PACs) decreased the proliferation of HCT116 and HT-29 colon cancer cells, induced apoptosis and reduced the formation of tumor colonies. Treatment of HCT116 colon cancer cells with cranberry polyphenols produced changes in expression of genes and proteins associated with the MAPK pathway, confirmed by microarray analysis, quantitative (Q)-PCR and Western blotting. Based on cranberry's effect in vitro, a feeding study was conducted ...


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