Chemicals and Drugs Commons^™

Pegylated Interferon Α-2b Up-Regulates Specific Cd8+ T Cells In Patients With Chronic Hepatitis B, Ji Chen, Yan Wang, Jun Li, Feng-Qin Hou, Gui-Qiang Wang

Pharmacology and Toxicology Faculty Publications

AIM: To investigate the effect of pegylated interferon (IFN) α-2b on specific CD8+ T lymphocytes in patients with chronic hepatitis B (CHB). METHODS: Twenty-one patients with CHB were treated with pegylated IFN α-2b. Periphery blood mononuclear cells were isolated from fresh heparinized blood by Ficoll-Hypaque density gradient centrifugation (density: 1.077 g/L, Pharmingen) at weeks 0, 4, 8, 12, and 24, respectively. Frequency of circulating hepatitis B virus (HBV) epitope-specific CD8 T cells was detected by flow cytometry. Cytokines were detected by cytometric bead assay. RESULTS: The frequency of circulating HBV core or env-specific CD8 T cells was higher (P …

Catch A Near Miss And Prevent A Harmful Error, Georgene Saliba Mba, Cphrm, Leroy Kromis, Kristie Lowery Rn, Bs, Cphq, Cphrm

Administration & Leadership

No abstract provided.

Development And Validation Of A Rapid Multi-Class Method For The Confirmation Of Fourteen Prohibited Medicinal Additives In Pig And Poultry Compound Feed By Liquid Chromatography Tandem Mass Spectrometry, Mark Cronly, Patrice Behan, Barry Foley, Liam Regan, Marella Gallagher, Sean Earley, Paula Shearan, Edward Malone

Articles

A confirmatory method has been developed to allow for the analysis of fourteen prohibited medicinal additives in pig and poultry compound feed. These compounds are prohibited for use as feed additives although some are still authorised for use in medicated feed. Feed samples are extracted by acetonitrile with addition of sodium sulphate. The extracts undergo a hexane wash to aid with sample purification. The extracts are then evaporated to dryness and reconstituted in initial mobile phase. The samples undergo an ultracentrifugation step prior to injection onto the LC-MS/MS system and are analysed in a run time of 26 minutes. The …

Characterization Of The Sero-Reactivity Of Proteins Map1152 And Map1156 From Mycobacterium Avium Subspecies Paratuberculosis, Avery L. Paulson

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne’s disease (JD) in ruminants. Development of genetic tools and completion of the MAP genome sequencing project expanded opportunities for antigen discovery. In this thesis, I review the current trends in diagnosis and disease control of JD and present the results of the studies on the seroreactivity of two proteins encoded for by the MAP1152-MAP1156 gene cluster. MAP1152 encodes for a PPE protein and MAP1156 encodes a diacylglycerol acyltransferase involved in triglyceride metabolism and classified in the uncharacterized protein family UPF0089. Maltose-binding protein (MBP) tagged recombinant MAP proteins were purified from Escherichia coli. …

An Archaeal Trna-Synthetase Complex That Enhances Aminoacylation Under Extreme Conditions, Vlatka Godinic-Mikulcic, Jelena Jaric, Corinne D. Hausmann, Michael Ibba, Ivana Weygand-Durasevic

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Aminoacyl-tRNA synthetases (aaRSs) play an integral role in protein synthesis, functioning to attach the correct amino acid with its cognate tRNA molecule. AaRSs are known to associate into higher-order multi-aminoacyl-tRNA synthetase complexes (MSC) involved in archaeal and eukaryotic translation, although the precise biological role remains largely unknown. To gain further insights into archaeal MSCs, possible protein-protein interactions with the atypical Methanothermobacter thermautotrophicus seryl-tRNA synthetase (MtSerRS) were investigated. Yeast two-hybrid analysis revealed arginyl-tRNA synthetase (MtArgRS) as an interacting partner of MtSerRS. Surface plasmon resonance confirmed stable complex formation, with a dissociation constant (KD) of 250 nm. Formation of the MtSerRS·MtArgRS complex …

Caval Agenesis With Hypoplastic Left Kidney In A Trauma Patient On Warfarin For Deep Vein Thrombosis (Poster), Ryan A. Lawless Md, Dale A. Dangleben Md

Department of Surgery

No abstract provided.

3,4-Methylenedioxymethamphetamine Alters Left Ventricular Function And Activates Nuclear Factor-Kappa B (Nf-Kappab) In A Time And Dose Dependent Manner, David A. Tiangco, Sapna Halcomb, Frank A. Lattanzio Jr, Barbara Y. Hargrave

Bioelectrics Publications

3,4-Methylenedioxymethamphetamine (MDMA) is an illicit psychoactive drug with cardiovascular effects that have not been fully described. In the current study, we observed the effects of acute MDMA on rabbit left ventricular function. We also observed the effects of MDMA on nuclear factor-kappa B (NF-kappa B) activity in cultured rat ventricular myocytes (H9c2). In the rabbit, MDMA (2 mg/kg) alone caused a significant increase in heart rate and a significant decrease in the duration of the cardiac cycle. Inhibition of nitric oxide synthase (NOS) by pretreatment with L-NAME (10 mg/kg) alone caused significant dysfunction in heart rate, systolic pressure, diastolic pressure, …

In Drag On Drugs, Ibpp Editor

International Bulletin of Political Psychology

Since commentators generally assert that the war on illegal and illicit drugs has been a failure, we should evaluate the assertion and, then, opine on why there is a war, winnable or not.

Reducing Overdose Deaths Associated With Pharmaceutical Opioid Treatment Of Chronic Pain: Analyzing Interventions With A System Dynamics Model, Wayne Wakeland

Systems Science Friday Noon Seminar Series

A dramatic rise in the use pharmaceutical opioids to treat pain, and the associated opioid abuse and addiction, has created a substantial public health problem in the United States. Effective tools and interventions are needed to identify policies to reduce opioid abuse, addiction, and overdose deaths. A system dynamics model is used to identify policy interventions that will reduce the prevalence of adverse outcomes attributed to pharmaceutical opioids. Results suggest that it will be difficult to minimize negative outcomes without adversely affecting the degree to which chronic pain patients can access pharmaceutical treatment, and also indicate the importance of the …

La Correlación Entre El Autoestima Y La Intención De Cambiar En Seis Ámbitos De La Vida De Un Fumador Adolescente., Aaron Picus

Independent Study Project (ISP) Collection

Background: According to a study in 2008 by the National Agency for the Control of Narcotics, 26.1% of Chilean adolescents between the ages of 12-18 had used tobacco at least once during the month of the study and 13% used tobacco daily. Even though smoking has negative health effects, many adolescents in Chile still smoke. Since the 1970s, low self-esteem has been proposed as a risk factor for the development of poor health behaviors. Recent investigations have shown that, when measured in the social, school, family, self-body image, sports and physical activity, and global realms of the life of an …

Total Protein Determination Using Micro Plate Assay, Julie Ruffatti

All Capstone Projects

One of the largest challenges that food manufactures are facing today is the management of food allergens. Allergenic protein in trace amounts, part per million concentrations, will trigger a reaction in some individuals. Food manufacturers need to prevent allergen cross-contamination by performing adequate sanitation after production of an allergenic containing food. Allergen detection kits are used to determine if sufficient protein was removed from the equipment surfaces during sanitation. One kit on the market is the 3M™ Clean- Trace™ Surface Protein (Allergen) swab tests. The test qualitatively detects the presence of protein based on the biuret reaction and will yield …

Synthesis And Analytical Evaluation Of Folate Conjugates For Use In Cancer Cell Detection, Sneha Reddy Kuthuru

All Capstone Projects

Recent clinical studies have shown the importance of folate receptor in drug delivery system as they increase the potency and reduce toxicity of many cancer therapies. The folate receptor alpha ( FR-a) binds with high affinity for folic acid and serves for receptor mediated transport of folate into cells. Folate is necessary for DNA metabolism and thus it is speculated that rapidly dividing cancer cells have an increased requirement for folic acid. It is known that FR-a levels are elevated in specific malignant diseases (solid tumors, leukemia) and thus the FR receptor serves as useful targeting moiety for the diagnosis …

Ranolazine Is Effective For Acute Or Chronic Ischemic Dysfunction With Heart Failure, Sudip Nanda Md, Facp, Matthew W. Martinez Md, Tanujit Dey Phd

Department of Medicine

No abstract provided.

Mechanisms Of Oxidant Generation By Catalase, Diane E. Heck, Michael Shakarjian, Hong-Duck Kim, Jeffrey Laskin, Anna M. Vetrano

NYMC Faculty Publications

The enzyme catalase converts solar radiation into reactive oxidant species (ROS). In this study, we report that several bacterial catalases (hydroperoxidases, HP), including Escherichia coli HP-I and HP-II also generate reactive oxidants in response to ultraviolet B light (UVB). HP-I and HP-II are identical except for the presence of NADPH. We found that only one of the catalases, HPI, produces oxidants in response to UVB light, indicating a potential role for the nucleotide in ROS production. This prompts us to speculate that NADPH may act as a cofactor regulating ROS generation by mammalian catalases. Structural analysis of the NADPH domains …

Religiosity, Spirituality And Attendance At Religious Services Among Recreational Drug Users: A Sub-Analysis Of The Drugnet Survey, Sohini Dhar

Masters Theses & Specialist Projects

This study is a sub-analysis ofthe previously collected cross-sectional DRUGNET survey data. The sample included 1,178 current users of illicit drugs and 389 former users. This study was delimited to U.S. citizens, aged 18 years and older, who completed the DRUGNET survey (n =1,567). DRUGNET was a descriptive online survey of self - reported attitudes and behaviors among a group of adult, self - identified drug users (i.e., not drug abusers). The purpose of the sub-analysis was to explore the importance of religion, spirituality, and religious service attendance in the context of an otherwise normal healthy adult life. Moreover, it …

High Pressure Liquid Chromatography Studies Of The Reaction Of Platinum Complexes With Peptides, Khaja Muneeruddin

Masters Theses & Specialist Projects

Platinum complexes (cisplatin, carboplatin and oxaliplatin) are effective anticancer agents. However the major drawbacks of platinum chemotherapy are toxic side effects and resistance. The affinity of platinum complexes to sulfur donor ligands of side chains of methionine and cysteine amino acids was assumed to be responsible for toxicity and resistance. Recently, it was found that the reaction of platinum complex with proteins containing sulfur donor ligands could actually favor its anticancer activity. Copper transporter 1 (Ctr 1), a protein involved in the transport of copper into the cell, also helps in the influx of cisplatin by binding to N-terminal domain …

Specific, Reversible Cytostatic Protection Of Normal Cells Against Negative Effects Of Chemotherapy, Benjamin B. Mull

Dissertations and Theses (Open Access)

Chemotherapy is a common and effective method to treat many forms of cancer. However, treatment of cancer with chemotherapy has severe side effects which often limit the doses of therapy administered. Because some cancer chemotherapeutics target proliferating cells and tissues, all dividing cells, whether normal or tumor, are affected. Cell culture studies have demonstrated that UCN-01 is able to reversibly and selectively arrest normal dividing cells; tumor cells lines do not undergo this temporary arrest. Following UCN-01 treatment, normal cells displayed a 50-fold increase in IC50 for camptothecin; tumor cells showed no such increased tolerance.

We have examined the response …

Poxa, Yjek And Elongation Factor P Coordinately Modulate Virulence And Drug Resistance In Salmonella Enterica, William Wiley Navarre, Shicong Zou, Hervé Roy, Jinglin Lucy Xie, Alexei Savchenko, Alexander Singer, Elena Edvokimova, Lynne R. Prost, Runjun Kumar, Michael Ibba, Ferric C. Fang

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We report an interaction between poxA, encoding a paralog of lysyl tRNA-synthetase, and the closely linked yjeK gene, encoding a putative 2,3-β-lysine aminomutase, that is critical for virulence and stress resistance in Salmonella enterica. Salmonella poxA and yjeK mutants share extensive phenotypic pleiotropy, including attenuated virulence in mice, an increased ability to respire under nutrient-limiting conditions, hypersusceptibility to a variety of diverse growth inhibitors, and altered expression of multiple proteins, including several encoded on the SPI-1 pathogenicity island. PoxA mediates posttranslational modification of bacterial elongation factor P (EF-P), analogous to the modification of the eukaryotic EF-P homolog, eIF5A, with …

Enalapril In Infants With Single Ventricle: Results Of A Multicenter Randomized Trial., Daphne T. Hsu, Victor Zak, Lynn Mahony, Lynn A. Sleeper, Andrew M. Atz, Jami C. Levine, Piers C. Barker, Chitra Ravishankar, Brian W. Mccrindle, Richard V. Williams, Karen Altmann, Nancy S. Ghanayem, Renee Margossian, Wendy K. Chung, William L. Border, Gail D. Pearson, Mario P. Stylianou, Seema Mital, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Angiotensin-converting enzyme inhibitor therapy improves clinical outcome and ventricular function in adults with heart failure. Infants with single-ventricle physiology have poor growth and are at risk for abnormalities in ventricular systolic and diastolic function. The ability of angiotensin-converting enzyme inhibitor therapy to preserve ventricular function and improve somatic growth and outcomes in these infants is unknown.

METHODS AND RESULTS: The Pediatric Heart Network conducted a double-blind trial involving 230 infants with single-ventricle physiology randomized to receive enalapril (target dose 0.4 mg . kg(-1) . d(-1)) or placebo who were followed up until 14 months of age. The primary end …

Role Of Pyridoxine 5'-Phosphate Oxidase In Metabolism And Transfer Of Pyridoxal 5'-Phosphate, Sayali Karve

Theses and Dissertations

Deficiency of vitamin B6 due to mutations in key B6 metabolizing enzymes is suspected to contribute to several pathologies. Vitamin B6 in its active form, pyridoxal 5’-phosphate (PLP) is a cofactor for over 140 known B6 requiring (or PLP-dependent) enzymes, that serve vital roles in many biochemical reactions. There are three primary vitamin B6 forms, pyridoxine (PN), pyridoxamine (PM) and pyridoxal (PL) which are phosphorylated to pyridoxine 5’-phosphate (PNP), pyridoxamine 5’-phosphate (PMP) and PLP respectively. Pyridoxal kinase (PLK) and pyridoxine 5’-phosphate oxidase (PNPO) are the key enzymes involved in both salvage and de novo pathways of PLP biosynthesis. Mutations in …

Pyridoxal Kinase: Its Role In Vitamin B6 Metabolism, Jigarkumar Desai

Theses and Dissertations

Pyridoxal kinase (PL kinase) and pyridoxine 5’-phosphate oxidase (PNP oxidase) are the two vitamin B6 salvage enzymes involved in metabolism of the primary inactive vitamin B6 (pyridoxal, pyridoxine and pyridoxamine) into the active cofactor form, pyridoxal 5’-phosphate (PLP). PLP, arguably the most important vitamin, is required by numerous vitamin B6 (PLP-dependent) enzymes as a co-factor. These enzymes serve vital roles in the metabolism of glucose, lipids, amino acids, heme, DNA/RNA and many neurotransmitters. High levels of vitamin B6 are linked to neurotoxicity, due to the non-specific interactions of PLP with non-B6 proteins. This problem is controlled, in part, by maintaining …

Redox Status Affects The Catalytic Activity Of Glutamyl-Trna Synthetase, Assaf Katz, Ranat Banerjee, Merly De Armas, Michael Ibba, Omar Orellana

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Glutamyl-tRNA synthetases (GluRS) provide Glu-tRNA for different processes including protein synthesis, glutamine transamidation and tetrapyrrole biosynthesis. Many organisms contain multiple GluRSs, but whether these duplications solely broaden tRNA specificity or also play additional roles in tetrapyrrole biosynthesis is not known. Previous studies have shown that GluRS1, one of two GluRSs from the extremophile Acidithiobacillus ferrooxidans, is inactivated when intracellular heme is elevated suggesting a specific role for GluRS1 in the regulation of tetrapyrrole biosynthesis. We now show that, in vitro, GluRS1 activity is reversibly inactivated upon oxidation by hemin and hydrogen peroxide. The targets for oxidation-based inhibition were …

Trial And Budget Analysis Of Two Synchronized Artificial Insemination Breeding Programs For Beef First Calf Heifers, John Nino

Agribusiness

This study was designed to compare the benefits and costs of two different synchronized artificial insemination programs on two groups of beef first calf heifers. A financial budget was developed that would include cost of synchronized insemination per animal and the added value of a bred heifer compared to an open one.

The two synchronized programs were called controlled internal drug release (CIDR) and Ovsynch. They used a specific timeline and drugs to complete the synchronization process. A single low birth weight high calving ease bull was used for both groups to enforce conformity between the groups. Costs of all …

Prostaglandin E(2) Is Crucial In The Response Of Podocytes To Fluid Flow Shear Stress., Tarak Srivastava, Ellen T. Mccarthy, Ram Sharma, Patricia A. Cudmore, Mukut Sharma, Mark L. Johnson, Lynda F. Bonewald

Manuscripts, Articles, Book Chapters and Other Papers

Podocytes play a key role in maintaining and modulating the filtration barrier of the glomerulus. Because of their location, podocytes are exposed to mechanical strain in the form of fluid flow shear stress (FFSS). Several human diseases are characterized by glomerular hyperfiltration, such as diabetes mellitus and hypertension. The response of podocytes to FFSS at physiological or pathological levels is not known. We exposed cultured podocytes to FFSS, and studied changes in actin cytoskeleton, prostaglandin E(2) (PGE(2)) production and expression of cyclooxygenase-1 and-2 (COX-1, COX-2). FFSS caused a reduction in transversal F-actin stress filaments and the appearance of cortical actin …

Fetal Programming By Nicotine Increases Cardiac Susceptibility To Ischemic Injury, Jennifer Charlotte Alexie Lawrence

Loma Linda University Electronic Theses, Dissertations & Projects

Fetal programming is the area of study that focuses on the prenatal origins of adult onset disorders. Previous studies have associated an adverse prenatal environment with the onset of physiologic and metabolic diseases during adulthood. Fetal malnutrition, hypoxia, and exposure to drugs - such as cocaine and nicotine - have been associated with adult disease states. Cigarette smoking is the number one cause of preventable death in the developed world. Among the many dangerous chemicals found in tobacco products is nicotine, the compound responsible for the addictive nature of tobacco use. Nicotine use during pregnancy is a known cause of …

Ricin B Chain-Insulin Fusion Protein Immunomodulation Of Type 1 Diabetes, James Edward Carter Iii

Loma Linda University Electronic Theses, Dissertations & Projects

Type 1 diabetes mellitus (T1D) is a debilitating chronic inflammatory disease of the insulin-producing pancreatic islet β-cells that results from a combination of genetic and environmental factors. Attempts to suppress Th1-mediated autoimmune diseases such as T1D by mucosal delivery of autoantigens for immunotolerization have yielded only partial success. Attainment of satisfactory levels of sustained immunological tolerance remains to be accomplished. To restore self-tolerance requires delivery of sufficient amounts of autoantigen to stimulate regulatory T helper cells that function to survey the gut and induce tolerance to consumed antigens such as food. Oral delivery of autoantigens has previously been shown to …

Key Data Gaps For Understanding Trends In Prescription Opioid Analgesic Abuse And Diversion Among Chronic Pain Patients And Nonmedical Users, Wayne W. Wakeland, John Fitzgerald, Aaron Gilson, J. David Haddox, Jack Homer, Lewis Lee, Louis Macovsky, Dennis Mccarty, Teresa D. Schmidt, Lynn Webster

Complex Systems Faculty Publications and Presentations

Population dynamics of medical and nonmedical prescription opioid usage and adverse outcomes were modeled. Critical parameter values were determined by their amount of influence on model behavior. Results suggest that closing these data gaps would help researchers to better identify ways to reduce the risk of adverse outcomes.

Discovery Of Quinic Acid Derivatives As Oral Anti-Inflammatory Agents, Kui Zeng

Theses and Dissertations (ETD)

Quinic acid (QA) esters found in hot water extracts of Uncaria tomentosa (a.k.a. Cat’s claw) exert anti-inflammatory activity through mechanisms involving inhibition of the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB). Herein, we described the synthesis and biological testing of novel QA derivatives. Inhibition of NF-κB was assessed using A549 (Type II alveolar epithelial-like) cells that stably express a secreted alkaline phosphatase (SEAP) reporter driven by an NF-κB response element. A549- NF-κB cells were stimulated with TNF-α (10 ng/mL) in the presence or absence of QA derivative for 18 hours followed by measurement of SEAP activity. Amide substitution at …

Characterization And Optimization Of Antigen-Specific T Cell Responses During Ex Vivo Expansion Of Melanoma Tumor-Infiltrating Lymphocytes, Yufeng Li

Dissertations and Theses (Open Access)

Treatment of metastatic melanoma with tumor reactive T cells (adoptive T cell therapy, ACT) is a promising approach associated with a high clinical response rate. However, further optimization of this treatment modality is required to increase the clinical response after this therapy. ACT in melanoma involves an initial phase (pre-REP) of tumor-infiltrating lymphocyte (TIL) expansion ex vivo from tumor isolates followed by a second phase, “rapid expansion protocol” (REP) generating the billions of cells used as the TIL infusion product. The main question addressed in this thesis was how the currently used REP affected the responsiveness of the CD8+ T …

Cip4 And Src In Promoting The Migration And Invasion Of Breast Cancers, Christina S. Pichot

Dissertations and Theses (Open Access)

Cellular invasion represents a critical early step in the metastatic cascade, and many proteins have been identified as part of an “invasive signature.” The non-receptor tyrosine kinase Src is commonly upregulated in breast cancers, often in conjunction with overexpression of EGFR. Signaling from this pathway stimulates cell proliferation, migration, and invasion and frequently involves proteins that regulate the cytoskeleton. My data demonstrates that inhibition of Src, using the small-molecule inhibitor dasatinib, impairs cellular migration and invasion. Furthermore, Src inhibition sensitizes the cells to the effects of the chemotherapeutic doxorubicin resulting in dramatic, synergistic inhibition of proliferation with combination treatments. The …