Medical Pharmacology Commons^™

Mitochondrial Lysyl-Trna Synthetase Independent Import Of Trna Lysine Into Yeast Mitochondria., Naresh Babu V Sepuri, Madhavi Gorla, Michael P King

Department of Biochemistry and Molecular Biology Faculty Papers

Aminoacyl tRNA synthetases play a central role in protein synthesis by charging tRNAs with amino acids. Yeast mitochondrial lysyl tRNA synthetase (Msk1), in addition to the aminoacylation of mitochondrial tRNA, also functions as a chaperone to facilitate the import of cytosolic lysyl tRNA. In this report, we show that human mitochondrial Kars (lysyl tRNA synthetase) can complement the growth defect associated with the loss of yeast Msk1 and can additionally facilitate the in vitro import of tRNA into mitochondria. Surprisingly, the import of lysyl tRNA can occur independent of Msk1 in vivo. This suggests that an alternative mechanism is present …

Seroprevalencia De Pestivirus De Rumiantes En Ovinos Reproductores De Una Empresa De La Sierra Central Del Perú, Nathalie A. Llancares, Hermelinda G. Rivera, Mariluz Araínga, Nestor Falcon P.

Journal Articles: Pharmacology & Experimental Neuroscience

The aim of the present study was to determine the prevalence of Bovine Viral Diarrhea Virus (BVDV) and Border Disease virus (BDV) in breeding sheep from a large cooperative farm in the Central highlands of Peru. Blood samples from apparently healthy sheep of 4 years old, both sexes (female = 165; male = 165) were collected for antibodies detection against BVDV and BDV using the virus neutralization test. The 2.1 ± 1.5% (7/330) and 28.5 ± 4.9% (94/330) of breeding sheep had antibodies against BVDV and BDV respectively, with antibodies titers of 1:2 and 1:16. There was significant association between …

Efficacy Of Infection Control Interventions In Reducing The Spread Of Multidrug-Resistant Organisms In The Hospital Setting, Joanna R. Wares, Erika M.C. D'Agata, Mary Ann Horn, Shigui Ruan, Glenn F. Webb

Department of Math & Statistics Faculty Publications

Multidrug-resistant organisms (MDRO) continue to spread in hospitals globally, but the population-level impact of recommended preventive strategies and the relative benefit of individual strategies targeting all MDRO in the hospital setting are unclear. To explore the dynamics of MDRO transmission in the hospital, we develop a model extending data from clinical individual-level studies to quantify the impact of hand hygiene, contact precautions, reducing antimicrobial exposure and screening surveillance cultures in decreasing the prevalence of MDRO colonization and infection. The effect of an ongoing increase in the influx of patients colonized with MDRO into the hospital setting is also quantified. We …

Sterol Lipid Metabolism In Down Syndrome Revisited: Down Syndrome Is Associated With A Selective Reduction In Serum Brassicasterol Levels, Gavin Tansley, Daniel T. Holmes, Dieter Lütjohann, Elizabeth Head, Cheryl L. Wellington

Pharmacology and Nutritional Sciences Faculty Publications

Over the past 15 years, insights into sterol metabolism have improved our understanding of the relationship between lipids and common conditions such as atherosclerosis and Alzheimer's Disease (AD). A better understanding of sterol lipid metabolism in individuals with Down Syndrome (DS) may help elucidate how this population's unique metabolic characteristics influence their risks for atherosclerosis and AD. To revisit the question of whether sterol lipid parameters may be altered in DS subjects, we performed a pilot study to assess traditional serum sterol lipids and lipoproteins, as well as markers of sterol biosynthesis, metabolites, and plant sterols in 20 subjects with …

Aging And Down Syndrome, Elizabeth Head, Wayne Silverman, David Patterson, Ira T. Lott

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.

C-Abl And Arg Drive Cancer Chemoresistance Via Activation Of Multiple Signaling Pathways, Jonathan Thomas Sims

Theses and Dissertations--Pharmacology and Nutritional Sciences

Despite 35 years of clinical trials, there has been little improvement in one-year survival rates with any chemotherapeutic regimen for the treatment of metastatic melanoma due to resistance to all known agents. Regardless of advances in detection and prevention, diagnosis of metastatic disease remains a death sentence. Resistance mechanisms, including aberrant kinase signaling and drug transport pumps, indicate a need for identification of other therapeutic targets that impinge upon multiple signaling pathways. The Abl family of non-receptor tyrosine kinases (c-Abl, Arg) has been indicted as a causative force in leukemia for more than three decades; however, their role in solid …

Characterization Of A Hyperthermophilic Redox Protein, Rubredoxin, As A Potential Targeted Cancer Therapeutic, Siri Lakshmi Chirumamilla

PCOM Biomedical Studies Student Scholarship

Cancer is an elusive neoplastic disease that claims the lives of many people around the world every year. Though treatments have become more specific to the different types of cancer, the need remains for antineoplastic drugs that target cancer cells and leave normal cells unharmed, with little to no systemic toxicity. The search for a targeted cancer therapeutic is necessary and urgent, and Pyrococcus furiosus rubredoxin might be such a tool. Rubredoxin is a small (53 amino acids), water soluble, non-heme iron electron transfer protein that contains an iron atom cofactor bound by the sulfurs of four cysteine residues, which …

Ethanol Interactions With Dl-Methylphenidate Versus D-Methylphenidate In Humans, Owen Reeves

MUSC Theses and Dissertations

Adult Attention-Deficit/Hyperactivity Disorder (ADHD) affects~ 4.4% of the adult population, and patients with this disorder frequently have comorbid substance abuse disorders. Methylphenidate (MPH) is considered a first line pharmacotherapy agent in the treatment of ADHD, and is commonly used or co-abused with alcohol. Hydrolysis of oral racemic methylphenidate (dl-MPH) by carboxylesterase 1 (CES1) limits the bioavailability of the pharmacologically active d-MPH isomer to approximately 30% and that of the inactive 1-MPH isomer to only 1-2%. Co-administration of dl-MPH with ethanol results in elevated d-MPH plasma concentrations, as well as CES1 mediated enantioselective transesterification of 1-MPH to 1-ethylphenidate (EPH). The present …

Targeting The Endocannabinoid System To Reduce Inflammatory Pain, Sudeshna Ghosh

Theses and Dissertations

The endogenous cannabinoids (endocannabinoids) anandamide (AEA) and 2-arachidonylglycerol (2-AG) exert their effects predominantly through cannabinoid CB1 and CB2 receptors, but these actions are short-lived because of rapid hydrolysis by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. Selective inhibition of either enzyme elevates CNS levels of the appropriate endocannabinoid and produces analgesic effects with fewer psychomimetic side effects than Δ9-tetrahydrocannabinol (THC), the primary active constituent of marijuana. While cannabinoid receptor agonists and FAAH inhibitors reliably produce anti-inflammatory and anti-hyperalgesic effects in the carrageenan test and other inflammatory pain models, much less is known about the consequences of inhibiting …

Artemis And Metnase Mediated Processing Of 3΄-Blocked Dna Lesions: Role In Radio/Chemoresistance And Dna Repair, Susovan Mohapatra

Theses and Dissertations

DNA double-strand breaks (DSB) with chemically modified end-termini are the most significant lesions resulting from radio/chemotherapeutic intervention of cancer and non homologous end-joining (NHEJ) factor Artemis nuclease has been implicated in the repair of such breaks. To examine whether the resolution of terminally blocked DNA DSBs is the biologically relevant function of Artemis, Artemis deficient fibroblasts were stably complemented with wild type or an endonuclease deficient D165N mutant Artemis. Physiological levels of wild type (WT) Artemis completely restored DSB repair proficiency and resistance to γ-radiation, bleomycin, and neocarzinostatin. Cells expressing the D165N mutants remained as chemo/radiosensitive and as repair deficient …

Is Etanercept A Safe And Effective Treatment For Ankylosing Spondylitis?, Robyn M. Albert

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this selective EBM review is to determine whether or not etanercept is a safe and effective treatment for ankylosing spondylitis (AS).

Study Design: Review of three English language randomized control trials published in 2007, 2008, and 2010.

Data Sources: Two double-blind placebo-controlled randomized controlled trials and one placebo-controlled randomized control trial comparing etanercept to placebo were found using PubMed.

Outcomes Measured: Work instability was measured through the Ankylosing Spondylitis Work Instability Scale (AS-WIS) based on scores of 1-20. Quality of life was measured through the EuroQOL-5D (EQ-5D), which assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. …

Is Dabigatran Non-Inferior To Warfarin For The Prevention Of Stroke In Those With Atrial Fibrillation?, Brittany Burlakoff

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not dabigatran 150 mg twice daily is non-inferior to warfarin for the prevention of stroke in those with atrial fibrillation with similar rates of bleeding events.

STUDY DESIGN: Review of 3 English language primary studies. All three trials were randomized controlled trials which were blinded for those receiving dabigatran and un-blinded for those receiving warfarin.

DATA SOURCES: Articles were found using PUBMED and COCHRANE databases.

OUTCOME MEASURED: The primary outcomes of these studies were either incidence of stroke or systemic embolism and/or major bleeding events.

RESULTS:The RE-LY …

Is 1.25 Mg Oral Fingolimod Effective In Reducing Relapses In Adults With Relapsing Multiple Sclerosis?, Caitlin M. Cook

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not is 1.25 mg oral fingolimod effective in reducing relapses in adults with relapsing multiple sclerosis.

STUDY DESIGN: Review of three English language primary studies published between 2006 and 2010.

DATA SOURCES: Randomized, double-blind, controlled clinical trials comparing daily 1.25 mg oral fingolimod to either identical placebo capsules or weekly intramuscular interferon beta-1a therapy were found using Pubmed and Cochrane Databases.

OUTCOMES MEASURED: Annualized relapse rate was assessed in all studies. Relapses were confirmed by neurologists and assessed using the Expanded Disability Status Scale (EDSS) to evaluate worsening …

Is Methylphenidate Transdermal System (Daytrana®) Safe And Effective For Managing Attention Deficit Hyperactivity Disorder Symptoms In Children?, Pamela Cassidy

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not methylphenidate transdermal system (Daytrana®) is safe and effective for managing attention deficit hyperactivity disorder symptoms in children.

STUDY DESIGN: A review of three English language studies published from 2006-2010. Includes two randomized, double-blind, controlled trials and one randomized, controlled crossover study.

DATA SOURCES: Randomized, placebo-controlled studies evaluating the effectiveness and safety of methylphenidate transdermal system (MTS) for managing attention deficit hyperactivity disorder (ADHD) symptoms in children were located using the PubMed, CINAHL, and Cochrane Library databases.

OUTCOMES MEASURED: The primary measures of effectiveness used were the …

Investigating The Role Of Α6 And Α4 Containing Neuronal Nicotinic Acetylcholine Receptors In Nicotine And Cocaine Conditioned Place Preference Tests In Mice., Sarah Sanjakdar

Theses and Dissertations

Neuronal nicotinic acetylcholine receptors modulate both cholinergic and non-cholinergic synaptic transmission. Our research concerns α6 and α4 neuronal nicotinic subunits because they often co-assemble with the β2 subunit, which has abundant expression in the CNS and previous work has demonstrated that β2* nAChRs are involved in nicotine and cocaine reward. α6β2* and α4β2* nAChRs are highly expressed in midbrain, which is known to be critical for the incentive salience associated with natural and artificial (drug) reward. Our goal was to assess the role of α6β2* and α4β2* nAChRs in nicotine and cocaine reward using an unbiased conditioned place preference (CPP) …

The Role Of High Affinity Nicotinic Acetylcholine Receptors On Anxiety-Like Behavior: A Study In Female Mice, Jessicka Hall

Theses and Dissertations

Tobacco dependence is high in women who suffer from anxiety disorders yet little is known about the contributions of nicotinic acetylcholine receptors (nAChRs) on anxiety-like behavior. β2*nAChRs (*denotes assembly with other subunits) are the most abundantly expressed nAChRs in the brain yet little is known about the contributions of β2*nAChRs on anxiety-like behavior in female mice. In this study, antagonism and nicotine effects on anxiety-like behavior was investigated across the life span in 6, 12 and 24-month-old drug-naïve knockout (KO), heterozygous (HET) and a gain of function α6L9S mice and wild type (WT). HET mice showed increased sensitivity to di-hydrobeta-erythroidine …

Striving For Zero Iv Pump Errors – A Unique Approach, Kristie Lowery Rn, Bs, Cphq, Cphrm, Gwenis L. Browning Rn, Msn, Georgene Saliba Rn, Bsn, Mba, Cphrm, Leroy Kromis Pharmd

Administration & Leadership

No abstract provided.

Cop9 Signalosome Component Jab1/Csn5 Is Necessary For T Cell Signaling Through Lfa-1 And Hiv-1 Replication., Shigemi M Kinoshita, Peter O Krutzik, Garry P Nolan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

To determine critical host factors involved in HIV-1 replication, a dominant effector genetics approach was developed to reveal signaling pathways on which HIV-1 depends for replication. A large library of short peptide aptamers was expressed via retroviral delivery in T cells. Peptides that interfered with T cell activation-dependent processes that might support HIV-1 replication were identified. One of the selected peptides altered signaling, lead to a difference in T cell activation status, and inhibited HIV-1 replication. The target of the peptide was JAB1/CSN5, a component of the signalosome complex. JAB1 expression overcame the inhibition of HIV-1 replication in the presence …

Triterpenoid Modulation Of Il-17 And Nrf-2 Expression Ameliorates Neuroinflammation And Promotes Remyelination In Autoimmune Encephalomyelitis, Tej K. Pareek, Abdelmadjid Belkadi, Sashi Kesavapany, Anita Zaremba, Sook L. Loh, Lianhua Bai, Mark L. Cohen, Colin Meyer, Karen T. Liby, Robert H. Miller, Michael B. Sporn, John J. Letterio

Dartmouth Scholarship

Inflammatory cytokines and endogenous anti-oxidants are variables affecting disease progression in multiple sclerosis (MS). Here we demonstrate the dual capacity of triterpenoids to simultaneously repress production of IL-17 and other pro-inflammatory mediators while exerting neuroprotective effects directly through Nrf2-dependent induction of anti-oxidant genes. Derivatives of the natural triterpene oleanolic acid, namely CDDO-trifluoroethyl-amide (CDDO-TFEA), completely suppressed disease in a murine model of MS, experimental autoimmune encephalomyelitis (EAE), by inhibiting Th1 and Th17 mRNA and cytokine production. Encephalitogenic T cells recovered from treated mice were hypo-responsive to myelin antigen and failed to adoptively transfer the disease. Microarray analyses showed significant suppression of …

Identifying Modulators Of The Development Of Acute Functional Tolerance To Ethanol In Caenorhabditis Elegans., Ka-Po Leung

Theses and Dissertations

Alcohol abuse is a problem in our society. There are few treatments available, in part due to the unclear molecular mechanisms of ethanol’s effects. Human studies indicate that there is a genetic component influencing disease susceptibility, and that an individual’s initial response to alcohol can predict their development of addiction. We have taken a forward genetics approach to study one component of initial response, acute functional tolerance (AFT), in Caenorhabditis elegans. We identified bet11, a mutation that causes animals to be defective in the development of AFT. Genetic analysis suggested that the gene that bet11 disrupts participates in a synthetic …