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Hexavalent Chromium-Induced Cytotoxicity And Mutagenicity: A Study Of Protection By Ascorbic Acid And Epigallocatechin Gallate, Timothy P. Mayotte 2019 Olivet Nazarene University

Hexavalent Chromium-Induced Cytotoxicity And Mutagenicity: A Study Of Protection By Ascorbic Acid And Epigallocatechin Gallate, Timothy P. Mayotte

Honors Program Projects

Hexavalent chromium, or Cr(VI), is a potent oxidizer and known carcinogen, that is found at varying levels in the water sources of more than 200 million Americans. However, the exact mechanism of carcinogenicity remains unknown, and though the government currently regulates total chromium levels, they have yet to determine a permissible exposure limit for Cr(VI). Moreover, there is currently no preventative treatment for Cr(VI). Because of Cr(VI)’s strong oxidative power, we hypothesized that it causes DNA mutation and cell death via oxidation and that antioxidants could prevent this from occurring. To test this, we first ...


Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara 2019 Southern Methodist University

Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara

Biological Sciences Theses and Dissertations

Multidrug resistance (MDR) is a major cause of chemotherapy failure. Overexpression of ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two well-studied drug transporters which are associated with MDR. These two transporters also act as a major functional unit of the blood brain barrier to protect the brain from xenobiotics and toxins. Lack of clinically approved P-gp and BCRP inhibitors renders chemotherapy treatments of many MDR cancers ineffective and obstructs drug uptake into the brain.

Using computational methods, we have identified new compounds that inhibit P-gp (Brewer et al., Mol. Pharmacol. 2014). Several of these ...


Xerostomia: A Comprehensive Review, Danevin Putrus 2019 Wayne State University

Xerostomia: A Comprehensive Review, Danevin Putrus

Honors College Theses

This thesis will be highlighting the condition known as Xerostomia. Xerostomia is the condition also known as “dry mouth”. This condition affects many people all throughout the world with symptoms causing bad breath, discomfort, difficulty speaking and many other. The seriousness of this condition can lead to cardiovascular disease, dementia, respiratory infections, diabetes mellitus, rheumatoid arthritis, and even cancer (Absolutedental.com). Currently there is not any one specific solution for the condition although many have been proposed. Throughout the thesis I will closely examine former research studies, current solutions proposed, and propose my own study and solution based on research ...


Brown Fat Organogenesis And Maintenance Requires Akt1 And Akt2, Joan Sanchez-Gurmaches, Camila Martinez Calejman, Su Myung Jung, Huawei Li, David A. Guertin 2019 University of Massachusetts Medical School

Brown Fat Organogenesis And Maintenance Requires Akt1 And Akt2, Joan Sanchez-Gurmaches, Camila Martinez Calejman, Su Myung Jung, Huawei Li, David A. Guertin

Open Access Articles

OBJECTIVE: Understanding the signaling mechanisms that control brown adipose tissue (BAT) development is relevant to understanding energy homeostasis and obesity. The AKT kinases are insulin effectors with critical in vivo functions in adipocytes; however, their role in adipocyte development remains poorly understood. The goal of this study was to investigate AKT function in BAT development.

METHODS: We conditionally deleted Akt1 and Akt2 either individually or together with Myf5-Cre, which targets early mesenchymal precursors that give rise to brown adipocytes. Because Myf5-Cre also targets skeletal muscle and some white adipocyte lineages, comparisons were made between AKT function in BAT versus white ...


Effect Of Tyrosine On The Productivity Of Pc12 Cells By Measuring Extracellular Atp Release, Sabrina Burkholder, Mary Rapmund, David Fogel, Jon Flees 2019 Chapman University

Effect Of Tyrosine On The Productivity Of Pc12 Cells By Measuring Extracellular Atp Release, Sabrina Burkholder, Mary Rapmund, David Fogel, Jon Flees

Student Scholar Symposium Abstracts and Posters

Given the challenge to “reverse-engineer the brain”, our group tried to address the problems of a lack of long term focus and attention span. Tyrosine was determined to aid in mental focus and brain productivity as it is a precursor to the neurotransmitter Dopamine. Given that Tyrosine is naturally occurring in the body, it is preferable to add to the body, whereas a substance like Adderall has negative effects, including increased heart rate that, over time, can cause cardiovascular damage. Drawing connections between in increase ATP and an increased ability to focus and perform under stress, extracellular ATP secretion of ...


Pediatric Ppi Use And Fractures, Nathan R. Fleishman, Troy Richardson, Thomas M. Attard 2019 Children's Mercy Hospital

Pediatric Ppi Use And Fractures, Nathan R. Fleishman, Troy Richardson, Thomas M. Attard

Posters

This study compared the rate of fracture among pediatric patients exposed to proton pump inhibitors to the rate among patients without exposure, and also considered the fracture location among children exposed to proton pump inhibitors.


Prospective Evaluation Of A Population Pharmacokinetic Model Of Pantoprazole For Obese Children, Alenka Chapron, Susan M. Abdel-Rahman, Valentina Shakhnovich 2019 Children's Mercy Hospital, Kansas City, MO

Prospective Evaluation Of A Population Pharmacokinetic Model Of Pantoprazole For Obese Children, Alenka Chapron, Susan M. Abdel-Rahman, Valentina Shakhnovich

Posters

We previously developed a population pharmacokinetic (popPK) model of pantoprazole for obese children. Our objective was to evaluate the predictive performance of this model in an independent cohort of normal weight, overweight and obese children.


Predictive Performance Of Existing Population Pharmacokinetic Models Of Tacrolimus In Pediatric Kidney Transplant Recipients, Alenka Chapron, Susan M. Abdel-Rahman 2019 Children's Mercy Hospital, Kansas City, MO

Predictive Performance Of Existing Population Pharmacokinetic Models Of Tacrolimus In Pediatric Kidney Transplant Recipients, Alenka Chapron, Susan M. Abdel-Rahman

Posters

With the goal of developing a clinician-driven tacrolimus (TAC) pharmacokinetic dosing tool, our initial objectives were 1) to examine whether published TAC population pharmacokinetic (popPK) models could serve as a foundation for the dosing tool, and 2) evaluate their performance predicting TAC concentrations in an independent cohort of Children's Mercy patients.


Synthesis Of A Zn(Ii)-Responsive Paracest Mri Agent For Improved Diagnosis Of Prostate Cancer, Megan Martin, Holly Clancy 2019 The University of San Francisco

Synthesis Of A Zn(Ii)-Responsive Paracest Mri Agent For Improved Diagnosis Of Prostate Cancer, Megan Martin, Holly Clancy

Creative Activity and Research Day - CARD

In the United States, prostate cancer is the leading type of cancer diagnosed in men. Prostate cancer is currently diagnosed with the Prostate-Specific Antigen (PSA) test; however, it leads to many false positives and therefore unneeded biopsies. Previous studies have shown that cancerous prostates have a much lower concentration of zinc than healthy prostates. The goal of this project is to create an MRI contrast agent capable of non-invasively quantifying zinc in the human prostate. Five out of the eight synthetic steps have been successfully completed so far, and the identities of these intermediate products have been verified by 1 ...


Effect Of Salt Concentration On Electrochemical Detection Of Dna, Ziming Dong, Eddie Madrigal, Ryan West Dr. 2019 University of San Francisco

Effect Of Salt Concentration On Electrochemical Detection Of Dna, Ziming Dong, Eddie Madrigal, Ryan West Dr.

Creative Activity and Research Day - CARD

Electrochemical approaches for biological sensing offer the potential advantages of facile sample preparation, fast response times, ease of parallel and multiplexed measurements, and the possibility of miniaturization (of sample sizes, electrodes, and associated electronics). All of these factors contribute towards the feasibility of electrochemical methods in biological sensing and analysis. This potential has already been achieved with the commercialization of blood glucose meters, which often rely on an electrochemical transduction mechanism. We have previously demonstrated the ability to electrochemically detect and differentiate complementary and mismatched DNA using our method of melting DNA duplexes at electrified gold surfaces, i.e. e-melting ...


Impact Of Quinoline Amide Substituents On The Luminescence And Paracest Mri Properties Of Bimodal Europium (Iii) Complexes, Brooke Aloe, Marisa Poveda, Osasere M. Evbuomwan 2019 The University of San Francisco

Impact Of Quinoline Amide Substituents On The Luminescence And Paracest Mri Properties Of Bimodal Europium (Iii) Complexes, Brooke Aloe, Marisa Poveda, Osasere M. Evbuomwan

Creative Activity and Research Day - CARD

Lanthanide ions exhibit optical imaging properties; however, the amount of energy needed to directly excite these ions could potentially be damaging to biological tissue. To overcome this limitation, organic chromophores, such as quinolines, can be used to absorb the excited light and transfer the energy obtained to the attached lanthanide ion. This intramolecular energy transfer results in the sensitization of the lanthanide ion luminescence. The goal of this project is to assess how the amide proton position in relation to the quinoline substituent affects the sensitivity of luminescence and the optical imaging properties of Europium (III) complexes. To achieve this ...


Ph Initiated Site Specific Drug Release, Brighton Mozer, Cailin Spencer, Seth Berkowitz, Connor Hague 2019 Carroll College

Ph Initiated Site Specific Drug Release, Brighton Mozer, Cailin Spencer, Seth Berkowitz, Connor Hague

Carroll College Student Undergraduate Research Festival

Studies have shown that unhealthy cells can have more acidic conditions in the cytoplasm. A medical application for this is to target unhealthy cells with vesicles containing a drug and then lyse when exposed to a more acidic environment. To demonstrate acidic pH-initiated cell lysing, sodium laurate was integrated into a dimyristoylphosphatidylcholine (DMPC) bilayer by sonicating the two organic compounds at a 1:1 ratio in a phenol red solution. Newly made vesicles contained phenol red, a chromophoric pH indicator that appears red in basic solutions, but yellow in acidic solutions. Vesicles will lyse as surrounding solution becomes more acidic ...


Sensory Primary Cilium Is A Responsive Camp Microdomain In Renal Epithelia, Rinzhin T. Sherpa, Ashraf M. Mohieldin, Rajasekharreddy Pala, Dagmar Wachten, Rennolds S. Ostrom, Surya M. Nauli 2019 Chapman University

Sensory Primary Cilium Is A Responsive Camp Microdomain In Renal Epithelia, Rinzhin T. Sherpa, Ashraf M. Mohieldin, Rajasekharreddy Pala, Dagmar Wachten, Rennolds S. Ostrom, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are hair-like cellular extensions that sense microenvironmental signals surrounding cells. The role of adenylyl cyclases in ciliary function has been of interest because the product of adenylyl cyclase activity, cAMP, is relevant to cilia-related diseases. In the present study, we show that vasopressin receptor type-2 (V2R) is localized to cilia in kidney epithelial cells. Pharmacologic inhibition of V2R with tolvaptan increases ciliary length and mechanosensory function. Genetic knockdown of V2R, however, does not have any effect on ciliary length, although the effect of tolvaptan on ciliary length is dampened. Our study reveals that tolvaptan may have a cilia-specific ...


Amphiphilic Peptides For Efficient Sirna Delivery, Saghar Mozaffari, Emira Bousoik, Farideh Amirrad, Robert Lamboy, Melissa Coyle, Ryley Hall, Abdulaziz Alasmari, Parvin Mahdipoor, Keykavous Parang, Hamidreza Montazeri Aliabadi 2019 Chapman University

Amphiphilic Peptides For Efficient Sirna Delivery, Saghar Mozaffari, Emira Bousoik, Farideh Amirrad, Robert Lamboy, Melissa Coyle, Ryley Hall, Abdulaziz Alasmari, Parvin Mahdipoor, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

A number of amphiphilic cyclic peptides—[FR]4, [WR]5, and [WK]5—containing hydrophobic and positively-charged amino acids were synthesized by Fmoc/tBu solid-phase peptide methods and evaluated for their efficiency in intracellular delivery of siRNA to triple-negative breast cancer cell lines, MDA-MB-231 and MDA-MB-468, in the presence and absence of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Among the peptides, [WR]5, which contains alternate tryptophan (W) and arginine (R) residues, was found to be the most efficient in the delivery of siRNA by improving the delivery by more than 3-fold when compared to other synthesized cyclic peptides that were not efficient ...


The Physiological Basis For Vitamin C As A Potential Treatment For Sepsis, Jennifer Johnston 2019 Butler University

The Physiological Basis For Vitamin C As A Potential Treatment For Sepsis, Jennifer Johnston

BU Well

Accounting for one third of all hospital patient deaths in America, sepsis remains one of the most deadly and complicated conditions that healthcare providers treat. Septic shock, a progressed form of sepsis, is even more troublesome, as mortality rates typically fall between 50-72%. It has been proposed that administration of high doses of vitamin C could be an effective treatment for the condition due to the nutrient’s anti-stress and anti-shock properties. This investigation of the physiological reasoning for administering high doses of vitamin C evaluates the viability of its use in patients with septic shock.


Nanomedicine For The Treatment Of Non-Hodgkin Lymphoma, Tanvi Gandhi, B.Pharm 2019 Butler University

Nanomedicine For The Treatment Of Non-Hodgkin Lymphoma, Tanvi Gandhi, B.Pharm

BU Well

Non-Hodgkin lymphoma, or NHL, is the predominant category of lymphoma. NHL is a type of lymphoid hematopoietic malignancy which approximately 70,000 Americans are diagnosed with annually, with the number of diagnoses growing annually. For decades, chemotherapy was the standard treatment of care, but since the discovery in 1997, monoclonal antibodies are increasingly used as an alternate form of therapy. Nonetheless, almost 20,000 Americans succumb to NHL annually, which highlights the translational gap between preclinical research and the market. Although a lot of progress has been made in therapy options by immunotherapy and combination chemotherapy, the ingenuity of nanomedicine ...


Air Quality And Employee Hygiene-Related Behavior In A Post Anesthesia Care Unit In Thailand, Somphorn Kampan 2019 Rajavithi Hospital

Air Quality And Employee Hygiene-Related Behavior In A Post Anesthesia Care Unit In Thailand, Somphorn Kampan

Asian / Pacific Island Nursing Journal

Post anesthesia care units (PACU) are sanitary spaces at hospitals. Bacterial and fungal contaminants in ambient air can pose significant threats to patient recovery. Excess waste anesthetic gases such as nitrous oxide and desflurane can also pose reproductive, genetic, and other health risks to PACU staff who suffer longterm exposure. Healthcare institutions routinely monitor and study PACU air quality as required by occupational health and safety acts and related regulations, and professional standards of care. This study presents recent data from a PACU intervention at Rajavithi Hospital in Bangkok, Thailand. Rajavithi took measurements of concentrations of airborne fungi, bacteria, desflurane ...


Synthesis And Antiproliferative Activities Of Conjugates Of Paclitaxel And Camptothecin With A Cyclic Cell-Penetrating Peptide, Naglaa Salem El-Sayed, Amir Nasrolahi Shirazi, Muhammad Imran Sajid, Shang Eun Park, Keykavous Parang, Rakesh Tiwari 2019 Chapman University

Synthesis And Antiproliferative Activities Of Conjugates Of Paclitaxel And Camptothecin With A Cyclic Cell-Penetrating Peptide, Naglaa Salem El-Sayed, Amir Nasrolahi Shirazi, Muhammad Imran Sajid, Shang Eun Park, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Cell-penetrating peptide [WR]5 has been previously shown to be an efficient molecular transporter for various hydrophilic and hydrophobic molecules. The peptide was synthesized using Fmoc/tBu solid-phase chemistry, and one arginine was replaced with one lysine to enable the conjugation with the anticancer drugs. Paclitaxel (PTX) was functionalized with an esterification reaction at the C20 hydroxyl group of PTX with glutaric anhydride and conjugated with the cyclic peptide [W(WR)4K(bAla)] in DMF to obtain the peptide-drug conjugate PTX1. Furthermore, camptothecin (CPT) was modified at the C(20)-hydroxyl group through the reaction with triphosgene. Then, it was ...


Eis Inhibitors, Sylvie Garneau-Tsodikova, Oleg V. Tsodikov 2019 University of Kentucky

Eis Inhibitors, Sylvie Garneau-Tsodikova, Oleg V. Tsodikov

Pharmaceutical Sciences Faculty Patents

Compounds and compositions are disclosed, which are useful as inhibitors of acetyltransferase Eis, a mediator of kanamycin resistance in Mycobacterium tuberculosis.


Rgd-Decorated Cholesterol Stabilized Polyplexes For Targeted Sirna Delivery To Glioblastoma Cells., Bo Lou, Kate Connor, Kieron Sweeney, Ian S. Miller, Alice C. O'Farrell, Eduardo Ruiz-Hernandez, David M. Murray, Garry P. Duffy, Alan Wolfe, Enrico Mastrobattista, Annette Byrne, Wim E. Hennink 2019 Utrecht University

Rgd-Decorated Cholesterol Stabilized Polyplexes For Targeted Sirna Delivery To Glioblastoma Cells., Bo Lou, Kate Connor, Kieron Sweeney, Ian S. Miller, Alice C. O'Farrell, Eduardo Ruiz-Hernandez, David M. Murray, Garry P. Duffy, Alan Wolfe, Enrico Mastrobattista, Annette Byrne, Wim E. Hennink

Physiology and Medical Physics Articles

The development of an effective and safe treatment for glioblastoma (GBM) represents a significant challenge in oncology today. Downregulation of key mediators of cell signal transduction by RNA interference is considered a promising treatment strategy but requires efficient, intracellular delivery of siRNA into GBM tumor cells. Here, we describe novel polymeric siRNA nanocarriers functionalized with cRGD peptide that mediates targeted and efficient reporter gene silencing in U87R invasive human GBM cells. The polymer was synthesized via RAFT copolymerization of N-(2-hydroxypropyl)-methacrylamide (HPMA) and N-acryloxysuccinimide (NAS), followed by post-polymerization modification with cholesterol for stabilization, cationic amines for siRNA complexation, and ...


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