Chemicals and Drugs Commons^™

Functional Interplay Between Chromatin Remodeling Complexes Rsc, Swi/Snf And Iswi In Regulation Of Yeast Heat Shock Genes, Tamara Y. Erkina, Y. Zou, S. Freeling, V. I. Vorobyev, Alexander M. Erkine

Scholarship and Professional Work – COPHS

Chromatin remodeling is an essential part of transcription initiation. We show that at heat shock gene promoters functional interactions between individual ATP-dependent chromatin remodeling complexes play critical role in both nucleosome displacement and Pol II recruitment. Using HSP12, HSP82 and SSA4 gene promoters as reporters, we demonstrated that while inactivation of SNF2, a critical ATPase of the SWI/SNF complex, primarily affects the HSP12 promoter, depletion of STH1- a SNF2 homolog from the RSC complex reduces histone displacement and abolishes the Pol II recruitment at all three promoters. From these results, we conclude that redundancy between SWI/SNF and RSC complexes …

Aspartame: A Sweet Toxin?, Atara Rena Degani

The Science Journal of the Lander College of Arts and Sciences

L-aspartyl-L-phenylalanyl-methyl ester, commonly known as aspartame, is one of the most widely used and controversial sweeteners. Many have questioned the safety of this chemical, concerned that it may be neurotoxic and carcinogenic. Numerous studies have been conducted on the three basic constituents of aspartame: aspartic acid, phenylalanine and methanol; scientists have tried to determine whether the ingestion of aspartame will cause a significant increase in blood plasma levels of these chemicals, and whether such an increase is dangerous. This review analyzes various studies conducted on the health effects of these metabolitic byproducts of aspartame.

Folic Acid And Neural Tube Defects, Rachel Leah Feinstein

The Science Journal of the Lander College of Arts and Sciences

The following is an excerpt of this article: Neural tube defects (NTD) are the most common types of birth defects. Research shows that folic acid taken periconceptionally greatly reduces the risk of having a NTD affected child. This paper will explain the role that folate plays in the metabolism, specifically in synthesizing methionine. It will bring evidence to show that methionine is crucial for normal neural tube development. In addition, it will explore the genetic factor involved in folate metabolism and possible folate deficiency.

Atherosclerosis And Antioxidants, Yehoshua Lewis

The Science Journal of the Lander College of Arts and Sciences

Cellular lipid oxidation is a known cause for the cascade leading to the formation of lipid laden foam cells, which can cause of atherosclerosis. While statins and antioxidants have recently come under question in the amelioration of atherosclerosis, Flavonoids have recently been touted as a powerful antioxidant and suppresser of atherosclerosis. This paper will attempt to show why statins and vitamin E have come under scrutiny, and how the desired effects of Flavonoids can be attributed to the role it plays in increased paraoxonase-1 activity (a known anti inflammatory associated with HDL), decreased C- Reactive protein activity, and increased nitric …

Pompe’S Disease And The Effects Of Alpha-Glucosidase Deficiency, Aaron Richler

The Science Journal of the Lander College of Arts and Sciences

The following is an excerpt from the introduction of this article: The energy that the body needs in order to function is obtained from carbohydrates that we get through our diet. These carbohydrates are monosacharides, disaccharides and polysacharides. The polysaccharides and disaccharides are hydrolyzed to monosaccharide’s such glucose (which comprises roughly 80%) fructose and galactose. Most cells convert the fructose and galactose to glucose. The body can use the glucose or store it. If energy is needed, glucose can be oxidized through the many reactions of glycolysis which gives a net production of 2 ATP and 2 NADH from one …

"A Cage Of Ovulating Females" : Mary Breckinridge And The Politics Of Contraception In Rural Appalachia, Dana Allen Johnson

Theses, Dissertations and Capstones

Mary Breckinridge and the Frontier Nursing Service have been the focus of intense scholarly effort over the last twenty years. Scholarship on Mary Breckinridge has centered on her healthcare reform work in Appalachia and its effects on the local residents and culture. This thesis examines the oral contraceptive trial that the FNS performed in Leslie County in the late 1950s and early 1960s. Although Breckinridge and the FNS maintained a restrictive contraceptive stance, they paradoxically permitted the contraceptive trial to be conducted on their patients in Leslie County. The decision to participate in the contraceptive trial resulted from a complex …

Interconversion Of The Specificities Of Human Lysosomal Enzymes, Ivan B. Tomasic

Masters Theses 1911 - February 2014

Fabry disease (FD) is an X-linked recessive lysosomal storage disorder (LSD) known to affect approximately 1 in every 40,000 males, and a smaller number of females. FD results from a deficiency of functional α-galactosidase (α-GAL), which leads to the accumulation of terminally α-galactosylated substrates in the lysosome. The predominant treatment is Enzyme Replacement Therapy (ERT), requiring the regular infusion of recombinant human α-GAL. More than half of individuals receiving ERT experience a range of adverse infusion reactions, and it has been reported that as many as 88% of patients receiving ERT develop neutralizing IgG antibodies against the drug.

In aim …

From Disco To Electronic Music: Following The Evolution Of Dance Culture Through Music Genres, Venues, Laws, And Drugs., Ambrose Colombo

CMC Senior Theses

Electronic dance music is a genre that has been long in the making. Starting with disco in the 1970s, dance culture genres evolved into house, acid house, techno, garage, 2-step, hardcore, gabba, san frandisco, electro, and many others. This paper studies the transformation of electronic sound, and the contributing/impeding factors involved. Drug use is heavily related to the creation and enjoyment of music, and features prominently in the history of dance culture. Starting with the use of acid in the 1960s and progressing to the use of acid, Quaaludes, poppers, speed in the 1970s, with MDA featured in clubs toward …

Differential Impact Of Tumor Suppressor Pathways On Dna Damage Response And Therapy-Induced Transformation In A Mouse Primary Cell Model., A Kathleen Mcclendon, Jeffry L Dean, Adam Ertel, Erik S Knudsen

Department of Cancer Biology Faculty Papers

The RB and p53 tumor suppressors are mediators of DNA damage response, and compound inactivation of RB and p53 is a common occurrence in human cancers. Surprisingly, their cooperation in DNA damage signaling in relation to tumorigenesis and therapeutic response remains enigmatic. In the context of individuals with heritable retinoblastoma, there is a predilection for secondary tumor development, which has been associated with the use of radiation-therapy to treat the primary tumor. Furthermore, while germline mutations of the p53 gene are critical drivers for cancer predisposition syndromes, it is postulated that extrinsic stresses play a major role in promoting varying …

Differential Control Of Tgm2 Expression By Oestrogen Receptor/Serms., Damian Lally

Masters

Breast cancer is a malignancy of the epithelial cells comprising the mammary gland. As the ER is necessary for the growth of pproximately 70% of breast cancers, pharmaceutical efforts have focused on uncovering modulators of the ERα such as antiestrogens and Selective Oestrogen Receptor Modulator (SERMs). SERMs differ from pure ER antagonists in their capacity to display tissue-selective and C promoter dependent agonist-antagonist activities. Tamoxifen (TAM) is a SERM that is used in the treatment of hormonally responsive breast cancer. TAM is the most commonly used treatment for patients with ERα positive breast cancer. In this study we examined the …

Oral Contraceptives: The Risks, Benefits, And Dilemmas, Courtney S. West

Senior Honors Theses

Millions of women have chosen to use oral contraceptives for various reasons. However, the question must be raised as to the awareness level of the risks and benefits associated with the use of oral contraceptives. Numerous studies have been performed to establish the effects of oral contraceptives. This thesis examines these studies to consolidate the most current findings.

In order to present these studies effectively, this thesis will begin by briefly summarizing the menstrual cycle and how the use of oral contraceptives affects menstruation. Following this, a review of the risks, benefits, and ethical dilemmas will be presented. Utilizing the …

Vitamin D3, Aryeh Grossman

The Science Journal of the Lander College of Arts and Sciences

The following is the introduction of this article: Vitamin D is the only vitamin that is free. It can be easily obtained from exposure to sunlight and yet more than 60% of Americans are Vitamin D deficient (Ginde et al., 2009; Bones, Vitamin D, and Calcium, n.d). The significance of Vitamin D can’t be emphasized enough and is often overlooked. Some its profound effects are apparent in the prevention of various diseases such as cancer, multiple sclerosis, and cardiovascular disease et cetera. Many lives can be spared each year just by taking Vitamin D. From cancer alone, 23,000 deaths can …

Ischemic Stroke Care - Official Guidelines From The Pakistan Society Of Neurology, Ayeesha Kamran Kamal, Ahmed Itrat, Imama Naqvi, Maria Khan, Roomasa Channa, Ismail Khatri, Mohammad Wasay

Department of Medicine

No abstract provided.

Reactive Oxygen Species Induced Cytokine Production And Cytotoxicity Of Pamam Dendrimers In J774a.1 Cells, Pratap Naha, Maria Davoren, Fiona Lyng, Hugh Byrne

Articles

The immunotoxicity of three generations of polyamidoamine (PAMAM) dendrimers (G-4, G-5 and G-6) was evaluated in mouse macrophage cells in vitro. Using the Alamar blue and MTT assays, a generation dependent cytotoxicity of the PAMAM dendrimers was found whereby G-6 > G-5 > G-4. The toxic response of the PAMAM dendrimers correlated well with the number of surface primary amino groups, with increasing number resulting in an increase in toxic response. An assessment of intracellular ROS generation by the PAMAM dendrimers was performed by measuring the increased fluorescence as a result of intracellular oxidation of Carboxy H2DCFDA to DCF both quantitatively using …

Pk/Pd Modelling Of Comb-Shaped Pegylated Salmon Calcitonin Conjugates Of Differing Molecular Weights, Sinead Ryan, Jesus Maria Frias, David H. Haddleton, David J. Brayden

Articles

Salmon calcitonin (sCT) was conjugated via cysteine-1 to novel combed-shaped end-functionalised poly(PEG) methyl ether methacrylate) (sCT-P) comb-shaped polymers, to yield conjugates of total molecular weights (MW) inclusive of sCT: 6.5, 9.5, 23 and 40 kDa. The conjugates were characterised by HPLC and their in vitro and in vivo bioactivity was measured by cAMP assay on human T47D cells and following intravenous (i.v.) injection to rats, respectively. Stability against endopeptidases, rat serum and liver homogenates was assessed. There were linear and exponential relationships between conjugate MW with potency and efficacy respectively, however the largest MW conjugate still retained 70% of E …

Prospects And Pits On The Path Of Biomimetics: The Case Of Tooth Enamel, Vuk Uskoković

Pharmacy Faculty Articles and Research

This review presents a discourse on challenges in understanding and imitating the process of amelogenesis in vitro on the molecular scale. In light of the analysis of imitation of the growth of dental enamel, it also impends on the prospects and potential drawbacks of the biomimetic approach in general. As the formation of enamel proceeds with the protein matrix guiding the crystal growth, while at the same time conducting its own degradation and removal, it is argued that three aspects of amelogenesis need to be induced in parallel: a) crystal growth; b) protein assembly; c) proteolytic degradation. A particular emphasis …

Intravenous Artesunate For Severe Malaria, Karl M. Hess, Jeffery A. Goad, Paul M. Arguin

Pharmacy Faculty Articles and Research

OBJECTIVE: To review the pharmacodynamics and pharmacotherapeutic use of intravenous artesunate for the treatment of severe malaria.

DATA SOURCES: Literature was retrieved through PubMed (1999 March 2010), MEDLINE (1996 March 2010), and the Centers for Disease Control and Prevention (CDC), using the search terms artemisinin, artesunate, malaria, and severe malaria. In addition, reference citations from publications identified were reviewed.

STUDY SELECTION AND DATA EXTRACTION: All articles in English that were identified from the data sources were reviewed. Focus was placed on post-marketing trials examining the safety and efficacy of artesunate in comparison with other regimens.

DATA SYNTHESIS …

Impaired M3 And Enhanced M2 Muscarinic Receptor Contractile Function In A Streptozotocin Model Of Mouse Diabetic Urinary Bladder, K. J. Pak, Rennolds S. Ostrom, M. Matsui, F. J. Ehlert

Pharmacy Faculty Articles and Research

We investigated the contractile roles of M2 and M3 muscarinic receptors in urinary bladder from streptozotocin-treated mice. Wild-type and M2 muscarinic receptor knockout (M2 KO) mice were given a single injection of vehicle or streptozotocin (125 mg kg−1) 2–24 weeks prior to bladder assays. The effect of forskolin on contractions elicited to the muscarinic agonist, oxotremorine-M, was measured in isolated urinary bladder (intact or denuded of urothelium). Denuded urinary bladder from vehicle-treated wild-type and M2 KO mice exhibited similar contractile responses to oxotremorine-M, when contraction was normalized relative to that elicited by KCl (50 mM). Eight to 9 weeks after …

Hcmv Pus28 Initiates Pro-Migratory Signaling Via Activation Of Pyk2 Kinase, Jennifer Totonchy, Susan Varnum, Ryan Melnychuk, Patricia Smith, Ljiliana Pasa-Tolic, Janani I. Shutthanadan, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Background: Human Cytomegalovirus (HCMV) has been implicated in the acceleration of vascular disease and chronic allograft rejection. Recently, the virus has been associated with glioblastoma and other tumors. We have previously shown that the HCMV-encoded chemokine receptor pUS28 mediates smooth muscle cell (SMC) and macrophage motility and this activity has been implicated in the acceleration of vascular disease. pUS28 induced SMC migration involves the activation of the protein tyrosine kinases (PTKs) Src and Focal adhesion kinase as well as the small GTPase RhoA. The PTK Pyk2 has been shown to play a role in cellular migration and formation of cancer, …

Synthesis Of Nucleoside 5′-O-Α,Β-Methylene-Β-Triphosphates And Evaluation Of Their Potency Towards Inhibition Of Hiv-1 Reverse Transcriptase, Yousef Ahmadibeni, Chandravanu Dash, M. J. Hanley, S. F. J. Le Grice, Hitesh K. Agarwal, Keykavous Parang

Pharmacy Faculty Articles and Research

A polymer-bound α,β-methylene-β-triphosphitylating reagent was synthesized and subjected to reactions with unprotected nucleosides, followed by oxidation, deprotection of cyanoethoxy groups, and acidic cleavage to afford nucleoside 5′-O-α,β-methylene-β-triphosphates. Among all the compounds, cytidine 5′-O-α,β-methylene-β-triphosphate inhibited RNase H activity of HIV-1 reverse transcriptase with a Ki value of 225 μM.