Chemicals and Drugs Commons^™

Relationship Between The Dimerization Of Thyroglobulin And Its Ability To Form Triiodothyronine, Cintia E. Citterio, Yoshiaki Morishita, Nada Dakka, Balaji Veluswamy, Peter Arvan

Pharmacy Faculty Articles and Research

Thyroglobulin (TG) is the most abundant thyroid gland protein, a dimeric iodoglycoprotein (660 kDa). TG serves as the protein precursor in the synthesis of thyroid hormones tetraiodothyronine (T₄) and triiodothyronine (T₃). The primary site for T₃ synthesis in TG involves an iodotyrosine acceptor at the antepenultimate Tyr residue (at the extreme carboxyl terminus of the protein). The carboxyl-terminal region of TG comprises a cholinesterase-like (ChEL) domain followed by a short unique tail sequence. Despite many studies, the monoiodotyrosine donor residue needed for the coupling reaction to create T₃ at this evolutionarily conserved …

Gene Regulation In The Hypothalamic-Pituitary-Gonadal Axis Of The Green Anole Lizard (Anolis Carolinensis)., Joshua N. Peters

All Graduate Theses, Dissertations, and Other Capstone Projects

Studies examining the hypothalamic-pituitary-gonad axis (HPG) in Anolis carolinensis provide insight into the regulation of this axis under extremely different reproductive conditions. Molecular studies indicate that kisspeptin proteins, transcribed from kiss1 and kiss2 genes, are produced in the hypothalamus where they bind G protein-coupled receptor 54 (GPR54), activating the HPG axis. Gonadotropin inhibitory hormone (GnIH) and its receptors, G protein-coupled receptor 147 and 74 (GPR147 and GPR74), down regulate HPG axis function. In this experiment we examined HPG axis gene expression in the green anole lizard (Anolis carolinensis), a seasonally breeding species with higher steroid hormone levels in the breeding …

De Novo Triiodothyronine Formation From Thyrocytes Activated By Thyroid-Stimulating Hormone, Cintia E. Citterio, Balaji Veluswamy, Sarah J. Morgan, Valerie A. Galton, J. Paul Banga, Stephen Atkins, Yoshiaki Morishita, Susanne Neumann, Rauf Latif, Marvin C. Gershengorn, Terry J. Smith, Peter Arvan

Pharmacy Faculty Articles and Research

The thyroid gland secretes primarily tetraiodothyronine (T₄), and some triiodothyronine (T₃). Under normal physiological circumstances, only one-fifth of circulating T₃ is directly released by the thyroid, but in states of hyperactivation of thyroid-stimulating hormone receptors (TSHRs), patients develop a syndrome of relative T₃ toxicosis. Thyroidal T₄ production results from iodination of thyroglobulin (TG) at residues Tyr⁵ and Tyr¹³⁰, whereas thyroidal T₃ production may originate in several different ways. In this study, the data demonstrate that within the carboxyl-terminal portion of mouse TG, T₃ is formed …

Impact Of Cyp2d6 Genotype On Amitriptyline Efficacy For The Treatment Of Diabetic Peripheral Neuropathy: A Pilot Study., Mamoonah Chaudhry, Marco Alessandrini, Jacobus Rademan, Tyren M. Dodgen, Francois E. Steffens, Danie G. Van Zyl, Andrea Gaedigk, Michael S. Pepper

Manuscripts, Articles, Book Chapters and Other Papers

AIM: Therapy with low-dose amitriptyline is commonly used to treat painful diabetic peripheral neuropathy. There is a knowledge gap, however, regarding the role of variable CYP2D6-mediated drug metabolism and side effects (SEs). We aimed to generate pilot data to demonstrate that SEs are more frequent in patients with variant CYP2D6 alleles.

METHOD: To that end, 31 randomly recruited participants were treated with low-dose amitriptyline for painful diabetic peripheral neuropathy and their CYP2D6 gene sequenced.

RESULTS: Patients with predicted normal or ultra-rapid metabolizer phenotypes presented with less SEs compared with individuals with decreased CYP2D6 activity.

CONCLUSION: Hence, CYP2D6 genotype contributes to …

Advances And Perspectives In Genetics Of Congenital Thyroid Disorders Associated With Thyroglobulin Gene Mutations, Héctor M. Targovnik, Cintia E. Citterio, Sofi Siffo, Carina M. Rivolta

Pharmacy Faculty Articles and Research

Dyshormonogenesis due to thyroglobulin (TG) gene mutations is a rare cause of congenital hypothyroidism with an estimated incidence of approximately 1 in 100,000 newborns. The TG gene is organized in 48 exons, spanning over 270 kb on human chromosome 8q24. The human TG mRNA is 8.5 Kb long and the preprotein monomer is composed of a 19 amino acids signal peptide followed by a 2749 residues polypeptide. Until now, one hundred seventeen deleterious mutations in the human TG gene have been identified and characterized, originating structural changes in the protein that alter the normal protein folding, assembly and …

Advances And Perspectives In Genetics Of Congenital Thyroid Disorders, Héctor M. Targovnik, Cintia E. Citterio, Sofi Siff, Carina M. Rivolta

Pharmacy Faculty Articles and Research

"Congenital hypothyroidism (CH) is the most frequent endocrine disease in infants, affects about 1 in 3,000 newborns and is characterized by elevated levels of thyroidstimulating hormone (TSH) as a consequence of reduced thyroid function. It is also one of the most common preventable causes of cognitive and motor deficits. Prevention of CH is based on carrier identification, genetic counseling and prenatal diagnosis. In neonates a complete diagnosis of CH should include clinical examination, biochemical thyroid tests, thyroid ultrasound, radioiodine or technetium scintigraphy and perchlorate discharge test (PDT). In the last two decades, considerable progress has been made in identifying the …

The Postfinasteride Syndrome; An Overview, David L. Rowland, Ion G. Motofei, Florian Popa, Vlad D. Constantin, Adriana Vasilache, Ioana Păunică, Cristian Bălălău, Georgeta P. Păunică, Petrisor Banu, Stana Păunică

Journal of Mind and Medical Sciences

As a 5-α reductase inhibitor, Finasteride has proven effective in ameliorating two conditions documented to be androgen dependent, namely male androgenic alopecia and benign prostatic hyperplasia. Therapeutic results are maintained as long as the drug is administered, with treatment cessation generally leading to the return of symptomatology for each condition. In addition, during the therapeutic phase, several adverse effects have been reported, some of which persist long or indefinitely after treatment cessation, known as “post-finasteride syndrome.”

Herein we present and discuss the most common finasteride side effects, along with a psycho-neuroendocrine rationale that could explain the persistence of many adverse …

Drug-Induced Nutrient Depletion, Rodney Richmond

College of Pharmacy Faculty Research ​and Publications

No abstract provided.

Effects Of Nox-1 Inhibition On Real-Time Blood Nitric Oxide And Hydrogen Peroxide In Acute Hyperglycemia, Ashley Mawhinney

PCOM Biomedical Studies Student Scholarship

Hyperglycemia has been associated with vascular endothelial dysfunction in part by a reduction in nitric oxide (NO) production and increased oxidative stress (e.g., increased superoxide (SO) and hydrogen peroxide (H₂O₂). Endothelial-derived NO can be significantly reduced by increased SO/H₂O₂ in part by the activation of NADPH oxidase during hyperglycemia. Of the 7 NADPH oxidase isoforms, NADPH oxidase isoform 1 (NOX1) is mainly expressed in the vasculature and may play a major role in hyperglycemia induced oxidative stress and vascular endothelial dysfunction. This hypothesis was tested by measuring blood NO and H2O2 levels in …

New-Onset Diabetes Mellitus With Exposure To Ledipasvir And Sofosbuvir., Resmi Premji, Nira Roopnarinesingh, Nazia Qazi, Eric S. Nylen

Medicine Faculty Publications

The combination therapy of ledipasvir/sofosbuvir was approved by the Food and Drug Administration in 2014 for the treatment of chronic hepatitis C. Although hyperglycemia is not well known to occur with its use, we present 2 cases of new-onset diabetes mellitus and a review of the literature suggesting an adverse event association. In the first patient with HIV, we postulate that ledipasvir/sofosbuvir increased the levels of tenofovir and thereby potentiated hyperglycemia. In the second case of a patient with prediabetes, ledipasvir/sofosbuvir appeared to increase insulin resistance. A literature review further supported an association of hyperglycemia and the use of ledipasvir/sofosbuvir. …

Ideology Masquerading As Science: The Case Of Endocrine Disrupter Screening Programmes, Troy Seidle

Troy Seidle, PhD

The global move to develop novel testing methods and strategies to identify suspected endocrine disrupting chemicals offers a unique opportunity to move away from traditional animal testing paradigms in this new area of regulatory concern. Regrettably, the programmes under development, both in the USA and internationally through the OECD, have thus far failed to consider in vitro and other nonanimal test methods as more than “pre-screening” or “priority-setting” tools in a larger, animal-based testing strategy. Validation efforts to date have focused almost exclusively on the modification of existing animal tests to detect “endocrine effects”, with no demonstrable effort to promote …

Control Of Inflammation In Pancreatic Β-Cells: Role Of Arylpyrazole Compounds, Whitney Lyn Powell

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

No abstract provided.

Metabolic Reprogramming Induced By Ketone Bodies Diminishes Pancreatic Cancer Cachexia, Surendra K. Shukla, Teklab Gebregiworgis, Vinee Purohit, Nina V. Chaika, Venugopal Gunda, Prakash Radhakrishnan, Kamiya Mehla, Iraklis I. Pipinos, Robert Powers, Fang Yu, Pankaj K. Singh

Robert Powers Publications

Background: Aberrant energy metabolism is a hallmark of cancer. To fulfill the increased energy requirements, tumor cells secrete cytokines/factors inducing muscle and fat degradation in cancer patients, a condition known as cancer cachexia. It accounts for nearly 20% of all cancer-related deaths. However, the mechanistic basis of cancer cachexia and therapies targeting cancer cachexia thus far remain elusive. A ketogenic diet, a high-fat and low-carbohydrate diet that elevates circulating levels of ketone bodies (i.e., acetoacetate, β-hydroxybutyrate, and acetone), serves as an alternative energy source. It has also been proposed that a ketogenic diet leads to systemic metabolic changes. Keeping in …

The Relationship Between Vitamin D Status Of Adult Women And Diet, Sun Exposure, Skin Reflectance, Body Composition, And Insulin Sensitivity, Marisa M. Mcadler

Master's Theses

As the prevalence of vitamin D deficiency continues to grow, mounting evidence supporting its link with chronic disease strengthens suggesting vitamin D’s candidacy in the prevention and treatment of multiple disease states and their complications. Dietary guidelines, however, do not take sun exposure into account. The present study sought to explore the impact of sun exposure on vitamin D status (serum 25(OH)D), and identify other significant determinants of serum levels which may have the greatest effects on overall health. Participants (n = 34) were pre-menopausal women aged 18 to 50 years (mean age 39 ± 6 years), who had their …

Transfusion Of Cxcr4-Primed Endothelial Progenitor Cells Reduces Cerebral Ischemic Damage And Promotes Repair In Db/Db Diabetic Mice, Ji Chen, Jianying Chen, Shuzhen Chen, Cheng Zhang, Liangqing Zhang, Xiang Xiao, Avik Das, Yuhui Zhao, Bin Yuan, Mariana Morris, Bin Zhao, Yanfang Chen

Pharmacology and Toxicology Faculty Publications

This study investigated the role of stromal cell-derived factor-1α (SDF-1α)/CXC chemokine receptor 4 (CXCR4) axis in brain and endothelial progenitor cells (EPCs), and explored the efficacy of CXCR4 primed EPCs in treating ischemic stroke in diabetes. The db/db diabetic and db/+ mice were used in this study. Levels of plasma SDF-1α and circulating CD34+CXCR4+ cells were measured. Brain SDF-1α and CXCR4 expression were quantified at basal and after middle cerebral artery occlusion (MCAO). In in vitro study, EPCs were transfected with adenovirus carrying null (Ad-null) or CXCR4 (Ad-CXCR4) followed with high glucose (HG) treatment for 4 days. For pathway block …

Post Gastric Bypass Hypoglycemia: Four Cases Treated Successfully With Alphaglucosidase Inhibitor Therapy, Shavon S. Frankhouser Do, Aakif N. Ahmad Do, Gretchen A. Perilli Md, Benjamin J. Quintana Md, Marc A. Vengrove Do, Facp

Department of Medicine

No abstract provided.

Compound 49b: A Novel Beta-Adrenergic Receptor Agonist In The Treatment Of Diabetic Retinopathy, Kimberly Williams-Guy

Theses and Dissertations (ETD)

Diabetic retinopathy is the leading cause of blindness in working Americans. While there are therapeutic regimens for the disease, more effective methods are needed. We have previously shown that a non-specific beta-adrenergic receptor agonist, isoproterenol, was effective in preventing functional and morphological changes associated with diabetic retinopathy in the rat. Isoproterenol also produced left ventricle remodeling suggesting it entered the systemic circulation. We therefore synthesized various novel beta-adrenergic receptor compounds and screened these compounds in vitro for their ability to reduce markers of inflammation and apoptosis. Of the various compounds tested, Compound 49b was able to reduce both inflammation and …

Measuring The Dynamic Surface Accessibility Of Rna With The Small Paramagnetic Molecule Tempol, Vincenzo Venditti, Neri Niccolai, Samuel E. Butcher

Vincenzo Venditti

The surface accessibility of macromolecules plays a key role in modulating molecular recognition events. RNA is a complex and dynamic molecule involved in many aspects of gene expression. However, there are few experimental methods available to measure the accessible surface of RNA. Here, we investigate the accessible surface of RNA using NMR and the small paramagnetic molecule TEMPOL. We investigated two RNAs with known structures, one that is extremely stable and one that is dynamic. For helical regions, the TEMPOL probing data correlate well with the predicted RNA surface, and the method is able to distinguish subtle variations in atom …

Structure And Thermodynamics Of A Conserved U2 Snrna Domain From Yeast And Human, Dipali G. Sashital, Vincenzo Venditti, Courtney G. Angers, Gabriel Cornilescu, Samuel E. Butcher

Vincenzo Venditti

The spliceosome is a dynamic ribonucleoprotein complex responsible for the removal of intron sequences from pre-messenger RNA. The highly conserved 5′ end of the U2 small nuclear RNA (snRNA) makes key base-pairing interactions with the intron branch point sequence and U6 snRNA. U2 stem I, a stem–loop located in the 5′ region of U2, has been implicated in spliceosome assembly and may modulate the folding of the U2 and U6 snRNAs in the spliceosome active site. Here we present the NMR structures of U2 stem I from human and Saccharomyces cerevisiae. These sequences represent the two major classes of U2 …

Longitudinal Study Of Plasma And Erythrocyte Selenium Levels In Type I Diabetic Children During Development And Treatment Of Ketoacidosis, Pi-Hsia Fan

Chemistry & Biochemistry Theses & Dissertations

Most studies on the biological activity of selenium have focused on its role at the active site in the ubiquitous enzyme, glutathione peroxidase (GSH-Px) which catalyzes the removal of hydrogen peroxide and organic hydroperoxides (1). A connection between selenium deficiency and a wide range of diseases in animals and humans has been reviewed (2). Development of various forms of human cancer (3), failure of the immune system (4), as well as some cardiovascular diseases (5) have been reported or suspected to correlate with selenium deficiency. However, the physiological function of selenium in these different diseases is not fully understood, and …