Medicine and Health Sciences Commons^™

Manganese Distribution Across The Blood-Brain Barrier. I. Evidence For Carrier-Mediated Influx Of Managanese Citrate As Well As Manganese And Manganese Transferrin, Janelle S. Crossgrove, David D. Allen, Bonny L. Bukaveckas, Susan S. Rhineheimer, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Manganese (Mn) is an essential element and a neurotoxicant. Regulation of Mn movement across the blood–brain barrier (BBB) contributes to whether the brain Mn concentration is functional or toxic. In plasma, Mn associates with water, small molecular weight ligands and proteins. Mn speciation may influence the kinetics of its movement through the BBB. In the present work, the brain influx rates of ⁵⁴Mn²⁺, ⁵⁴Mn citrate and ⁵⁴Mn transferrin (⁵⁴Mn Tf) were determined using the in situ brain perfusion technique. The influx rates were compared to their predicted diffusion rates, which were determined from …

Legal Movements In Intellectual Property: Trips, Unilateral Action, Bilateral Agreements, And Hiv/Aids, Margo A. Bagley

Faculty Articles

This Article begins with an overview of the relationship between the Agreement on Trade-Related Aspects of Intellectual Property Rights (the "TRIPS Agreement") and the HIV/AIDS pandemic which created the need for the Doha Declaration. It then discusses two trade-related movements, unilateral action and TRIPS-plus bilateral agreements, that call into question the long-term effectiveness of the TRIPS Agreement process, generally, and the benefits of the Doha Declaration, in particular, in addressing multiple facets of the access to essential medicines problem. This Article concludes that a consideration of these issues should be included in the development of any further TRIPS-related solutions to …

Angiotensin Ii Enhances Adenylyl Cyclase Signaling Via Ca2+/Calmodulin. Gq-Gs Cross-Talk Regulates Collagen Production In Cardiac Fibroblasts, Rennolds S. Ostrom, Jennifer E. Naugle, Miki Hase, Caroline Gregorian, James S. Swaney, Paul A. Insel, Laurence L. Brunton, J. Gary Meszaros

Pharmacy Faculty Articles and Research

Cardiac fibroblasts regulate formation of extracellular matrix in the heart, playing key roles in cardiac remodeling and hypertrophy. In this study, we sought to characterize cross-talk between Gq and Gs signaling pathways and its impact on modulating collagen synthesis by cardiac fibroblasts. Angiotensin II (ANG II) activates cell proliferation and collagen synthesis but also potentiates cyclic AMP (cAMP) production stimulated by β-adrenergic receptors (β-AR). The potentiation of β-AR-stimulated cAMP production by ANG II is reduced by phospholipase C inhibition and enhanced by overexpression of Gq. Ionomycin and thapsigargin increased intracellular Ca2+ levels and potentiated isoproterenol- and forskolin-stimulated cAMP production, whereas …

What Are The Elements Of A Successful Training Model, As Perceived By Global Corporate Security Heads Working In The Ethical Pharmaceutical Industry?, Kevin P. Schatzle

Seton Hall University Dissertations and Theses (ETDs)

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Hemorrhagic Fever Viruses, Jeffery A. Goad, J Nguyen

Pharmacy Faculty Articles and Research

Viral hemorrhagic fever (VHF) viruses are diverse and include arenaviruses, bunyaviruses, filoviruses, and flaviviruses. Lassa fever, South American hemorrhagic fever (HF), Rift Valley HF, Crimean-Congo HF, Ebola, Marburg, yellow fever, and dengue fever are well known examples of the hemorrhagic fever viruses. They are often difficult to diagnose and treat resulting in significant morbidity and mortality. Transmission varies from vector borne to person-to-person. The common clinical presentation includes fever, myalgia, microvascular damage, and hemorrahage as well as a history of travel to the tropics. If VHF is suspected, strict infection control procedures must be implemented to prevent the spread of …

Evaluation Of 10-Fold Cross Validation And Prediction Error Sums Of Squares Statistic For Population Pharmacokinetic Model Validation, Shibani Harite

University of the Pacific Theses and Dissertations

It was the objective of the current study to evaluate the ability of 10-fold cross validation and prediction error sum of squares (PRESS) statistic to identify population pharmacokinetic models (PPKM) that were estimated from data without influence observations versus PPKMs from data containing influence observations. The evaluation of 10-fold cross validation and PRESS statistic from Leave-one-out cross-validation for PPK model validation was performed in 3 Phases. In Phase 1 model parameters (theta and clearance) were estimated for datasets with and without influence observations. It was found that influence observations caused an over-estimation of the model parameters.

Synthases, Joseph Chappell, Kathleen R. Manna, Joseph P. Noel, Courtney M. Starks

Pharmaceutical Sciences Faculty Patents

Novel synthases and the corresponding nucleic acids encoding such synthases are disclosed herein. Such synthases possess an active site pocket that includes key amino acid residues that are modified to generate desired terpenoid reaction intermediates and products. Synthase modifications are designed based on, e.g., the three-dimensional coordinates of tobacco 5-epi-aristolochene synthase with or without a substrate bound in the active site.

An Overview Of Progress In The International Regulation Of The Pharmaceutical Industry, Joan Costa-Font, Aaron Burakoff Harvard University; University Of Barcelona

The University of New Hampshire Law Review

[Excerpt] “The pharmaceutical industry, a significant source of healthcare throughout the world, has several features that distinguish it from the rest of the health industry. In the last half-century, new technology, better technological know-how, and overall economic growth have led to widespread and rapid growth in the pharmaceutical sector. Advancements in pharmaceutical research and development have led to the production of drugs that can routinely combat afflictions that, only years ago, were untreatable or even fatal. Since 1970, the average share of Gross Domestic Product (GDP) on pharmaceutical goods has increased in most Organization for Economic Cooperation and Development (OECD) …

A Study Of 5-Aminolevulinic Acid And Its Methyl Ester Used In In Vitro And In Vivo Systems Of Human Bladder Cancer, Vanaja Manivasager, Paul Wan Sia Heng, Jinsong Hao, Wei Zheng, Khee Chee Soo, Malini Olivo

Pharmaceutical Science and Research

The use of 5-aminolevulinic acid and its esters to induce endogenous porphyrins for the purpose of detection of epithelial cancers is being studied extensively in many centres around the world. The challenge is to prepare an efficacious formulation for the purpose of cancer detection. Photodynamic diagnosis of cancer using 5-aminolevulinic acid (ALA) and its ester derivatives is being actively investigated. In this study, we compared ALA with ALA methyl ester (AME) derivative in terms of PpIX fluorescence intensity in in vitro and in vivo systems of bladder carcinoma. For the in vivo system consisting of RT112 xenografts, the modes of …

Research News: 2002, No. 3, University Of Mississippi. School Of Pharmacy

Research News: Grants and Publications (2000-2014)

Grants, publications, technology transfer, special announcements

Methods Of Making Modified Polypeptides, Joseph Chappell, Kathleen R. Manna, Joseph P. Noel, Courtney M. Starks

Pharmaceutical Sciences Faculty Patents

Novel polypeptides and the corresponding nucleic acids encoding such polypeptides are disclosed herein. The invention provides methods of making modified polypeptides by altering one or more amino acid residues involved in the active site of a preselected polypeptide.

Ang Ii At(1) And At(2) Receptors In Developing Kidney Of Normal Microswine, Susan P. Bagby, Linda S. Lebard, Zaiming Luo, Bryan E. Ogden, Christopher Corless, Elizabeth D. Mcpherson, Robert C. Speth

HPD Articles

To identify an appropriate model of human renin-angiotensin system (RAS) involvement in fetal origins of adult disease, we quantitated renal ANG II AT(1) and AT(2) receptors (AT1R and AT2R, respectively) in fetal (90-day gestation, n = 14), neonatal (3-wk, n = 5), and adult (6-mo, n = 8) microswine by autoradiography ((125)I-labeled [Sar(1)Ile(8)]ANG II+cold CGP-42112 for AT1R, (125)I-CGP-42112 for AT2R) and by whole kidney radioligand binding. The developmental pattern of renal AT1R in microswine, like many species, exhibited a 10-fold increase postnatally (P < 0.001), with maximal postnatal density in glomeruli and lower density AT1R in extraglomerular cortical and outer medullary sites. With aging, postnatal AT1R glomerular profiles increased in size (P < 0.001) and fractional area occupied (P < 0.04), with no change in the number per unit area. Cortical levels of AT2R by autoradiography fell with age from congruent with 5,000 fmol/g in fetal kidneys to congruent with 60 and 20% of fetal levels in neonatal and adult cortex, respectively (P < 0.0001). The pattern of AT2R binding in postnatal pig kidney mimicked that described in human and simian, but not rodent, species: dense AT2R confined to discrete cortical structures, including pre- and juxtaglomerular, but not intraglomerular, vasculature. Our results provide a quantitative assessment of ANG II receptors in developing pig kidney and document the concordance of pigs and primates in developmental regulation of renal AT1R and AT2R.

Brain Uptake, Retention, And Efflux Of Aluminum And Manganese, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

My colleagues and I investigated the sites and mechanisms of aluminum (Al) and manganese (Mn) distribution through the blood-brain barrier (BBB). Microdialysis was used to sample non-protein-bound Al in the extracellular fluid (ECF) of blood (plasma) and brain. Brain ECF Al appearance after intravenous Al citrate injection was too rapid to attribute to diffusion or to transferrin-receptor-mediated endocytosis, suggesting another carrier-mediated process. The brain:blood ECF Al concentration ratio was 0.15 at constant blood and brain ECF Al concentrations, suggesting carrier-mediated brain Al efflux. Pharmacological manipulations suggested the efflux carrier might be a monocarboxylate transporter (MCT). However, the lack of Al …

Pharmacy Newsletter : October 2002, Pharmacy Department

Department of Pharmacy Archives

Content:

• Drug Utilization Review

Cis-2,6-Disubstituted Piperidines For The Treatment Of Psychostimulant Abuse And Withdrawal, Eating Disorders, And Central Nervous System Diseases And Pathologies, Linda P. Dwoskin, Peter A. Crooks, Marlon D. Jones

Pharmaceutical Sciences Faculty Patents

Cis-2,6-disubstituted piperdine analogs, or lobeline analogs, having the general formula:

To see the remainder of this abstract, please download this patent.

Ipr : Pharmaceuticals, Rupa Chanda

IIMB Management Review

In the introductory panel of the Conference on IPR, the speakers included S Chandrasekaran, Deputy Controller of Patents & Designs, Govt of India; M D Nair, Consultant to the Pharmaceutical Industry, Chennai; P P Prabhu, former Commerce Secretary, Government of India; K Raghavendra Rao, MD, Orchid Chemicals & Pharmaceuticals and Jayashree Watal, Consultant to the WTO Secretariat. S Chandrasekaran clarified what constitutes intellectual property, what a patent is, and how an invention may qualify for a patent.He pointed out that as a participant in the TRIPS Agreement, India is obliged to modify her statutes to make her IPR regime TRIPS …

Macro-Microscopic Fluorescence Imaging Of Human Npc Xenografts In A Murine Model Using Topical Vs. Intravenous Administration Of 5-Aminolevulinic Acid, Vanaja Manivasager, Paul Wan Sia Heng, Jinsong Hao, Wei Zheng, Khee Chee Soo, Malini Olivo

Pharmaceutical Science and Research

The use of 5-aminolevulinic acid to induce endogenous porphyrins for the purpose of detection of epithelial cancers is being studied extensively in many centres around the world. The challenge is to prepare an efficacious formulation of 5-ALA for the purpose of cancer detection. In this study, we compared two formulations of topical 5-ALA applications with intravenous administration in NPC/CNE-2 xenografts on balb/c nude mice. One of the formulations was a gantrez muco-adhesive patch and the other was a polyvinyl-pyrolidone muco-adhesive patch. The Karl Storz fluorescence endoscopy system was used to obtain macroscopic fluorescence images. Microscopic fluorescence imaging was done by …

Water Soluble Amine Esters Of Testosterone For Intranasal Administration, Anwar A. Hussain

Pharmaceutical Sciences Faculty Patents

The present invention provides novel water soluble testosterone analogs. These testosterone analogs are suitable for intranasal administration to patients requiring increased plasma testosterone levels. The present invention also provides pharmaceutical compositions containing the testosterone analogs of the present invention. The present invention further provides a method of increasing plasma testosterone levels in patients in need of such treatment comprising the intranasal administration of the water-soluble testosterone analogs and pharmaceutical compositions of the present invention.

Retirees And Pharmaceutical Costs: Is There Really A Crisis?, Justine Maiello

Seton Hall University Dissertations and Theses (ETDs)

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Research News: 2002, No. 2, University Of Mississippi. School Of Pharmacy

Research News: Grants and Publications (2000-2014)

Grants, publications, technology transfer, special announcements

Camptothecin Analogs And Methods Of Preparation Thereof, Dennis P. Curran, Bom David, Thomas Burke

Pharmaceutical Sciences Faculty Patents

To see this abstract, please download this patent.

Morphine-6-Sulfate Analogues And Their Use For The Treatment Of Pain, Peter A. Crooks, Abdulghani A. Houdi, Santosh G. Kottayil, D. Allan Butterfield

Pharmaceutical Sciences Faculty Patents

3-O-Acetylmorphine-6-sulfate analogues are potent, centrally-acting morphine derivatives. The compounds are useful for the treatment of pain.

Timing Of New Black Box Warnings And Withdrawals For Prescription Medications, Karen Lasser, Paul D. Allen, Steffie Woolhandler, David U. Himmelstein, Sidney M. Wolfe, David H. Bor

Publications and Research

Context Recently approved drugs may be more likely to have unrecognized adverse drug reactions (ADRs) than established drugs, but no recent studies have examined how frequently postmarketing surveillance identifies important ADRs.

Objective To determine the frequency and timing of discovery of new ADRs described in black box warnings or necessitating withdrawal of the drug from the market.

Design and Setting Examination of the Physicians' Desk Reference for all new chemical entities approved by the US Food and Drug Administration between 1975 and 1999, and all drugs withdrawn from the market between 1975 and 2000 (with or without a prior black …

Research News: 2002, No. 1, University Of Mississippi. School Of Pharmacy

Research News: Grants and Publications (2000-2014)

Grants, publications, technology transfer

Triplet Repeat Dna Structures And Human Genetic Disease: Dynamic Mutations From Dynamic Dna., Richard R. Sinden, Vladimir N. Potaman, Elena A. Oussatcheva, Christopher E. Pearson, Yuri L. Lyubchenko, Luda S. Shlyakhtenko

Journal Articles: Pharmaceutical Sciences

Fourteen genetic neurodegenerative diseases and three fragile sites have been associated with the expansion of (CTG)n (CAG)n, (CGG)n (CCG)n, or (GAA)n (TTC)n repeat tracts. Different models have been proposed for the expansion of triplet repeats, most of which presume the formation of alternative DNA structures in repeat tracts. One of the most likely structures, slipped strand DNA, may stably and reproducibly form within triplet repeat sequences. The propensity to form slipped strand DNA is proportional to the length and homogeneity of the repeat tract. The remarkable stability of slipped strand DNA may, in part, be due to loop-loop interactions facilitated …

Glutamine Uptake By Neurons: Interaction Of Protons With System A Transporters, Farrukh A. Chaudhry, Dietmar Schmitz, Richard J. Reimer, Peter Larsson, Andrew T. Gray, Roger Nicoll, Michael Kavanaugh, Robert H. Edwards

Biomedical and Pharmaceutical Sciences Faculty Publications

Astrocytes provide the glutamine required by neurons to synthesize glutamate and GABA. However, the mechanisms involved in glutamine transfer from glia to neurons have remained poorly understood. Recent work has implicated the System N transporter SN1 in the efflux of glutamine from astrocytes and the very closely related System A transporters SA1 and SA2 in glutamine uptake by neurons. To understand how these closely related proteins mediate flux in different directions, we have examined their ionic coupling. In contrast to the electroneutral exchange of H⁺ for Na⁺ and neutral amino acid catalyzed by SN1, we now show that …

Dynamic Equilibrium Between Coupled And Uncoupled Modes Of A Neuronal Glutamate Transporter, Lars Borre, Michael Kavanaugh, Baruch I. Kanner

Biomedical and Pharmaceutical Sciences Faculty Publications

In the brain, the neurotransmitter glutamate is removed from the synaptic cleft by (Na⁺ + K⁺)-coupled transporters by an electrogenic process. Moreover, these transporters mediate a sodium- and glutamate-dependent uncoupled chloride conductance. In contrast to the wild type, the uptake of radiolabeled substrate by the I421C mutant is inhibited by the membrane-impermeant [2-(trimethylammonium)ethyl]methanethiosulfonate and also by other sulfhydryl reagents. In the wild-type and the unmodified mutant, substrate-induced currents are inwardly rectifying and reflect the sum of the coupled electrogenic flux and the anion conductance. Remarkably, the I421C mutant modified by sulfhydryl reagents exhibits currents that are non-rectifying …

On The Evolution Of Depression, Mike W. Martin

Philosophy Faculty Articles and Research

In "Depression as a Mind-Body Problem," Walter Glannon outlines a psychosocial-physiological explanation of depression as a psychological response to chronic stress—today, especially social stress—in which cortisol imbalances disrupt neurotransmitters. Accordingly, treatment for depression should combine psychopharmacology and psychotherapy—a valuable reminder in light of the current restrictions on funding for health care (Hobson and Leonard 2001). My comments focus, however, on Glannon's objections to evolutionary theorists who explain our capacity for depression as adaptive to the natural and social environment. His objections are implausible because he fails to distinguish depression as a mood and a disorder.

Pick-Me-Up Newsletter - Issue 1, Volume 2, Nova Southeastern University

Pick Me Up Newsletter

No abstract provided.

Pick-Me-Up Newsletter - Issue 4 , Volume 1, Nova Southeastern University

Pick Me Up Newsletter

No abstract provided.