Pharmacy and Pharmaceutical Sciences Commons^™

Preliminary Biochemical Characterization Of The Novel, Non-At1, Non-At2 Angiotensin Binding Site From The Rat Brain, Vardan T. Karamyan, Jason Arsenault, Emanuel Escher, Robert C. Speth

HPD Articles

A novel binding site for angiotensins II and III was recently discovered in brain membranes in the presence of the sulfhydryl reactive angiotensinase inhibitor parachloromercuribenzoate. This binding site is distinctly different from the other known receptors for angiotensins: AT₁, AT₂, AT₄, and mas oncogene protein (Ang 1-7 receptor). Preliminary biochemical characterization studies have been done on this protein by crosslinking it with (125)I-labeled photoaffinity probes and solubilizing the radiolabeled binding site. Polyacrylamide gel electrophoresis studies and isoelectric focusing indicate that this membrane bound binding site is a protein with a molecular weight of 70-85 kDa and an isoelectric point of …

Sizing Up Pharmacotherapy For Obesity., Michael A. Valentino, Andre Terzic, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Obesity has increased over the last 20 years, from a condition affecting only a small portion of populations in developed countries, into a global pandemic. The impact of obesity can be appreciated in the context of the populations at risk, and it is estimated that >1 billion adults worldwide are overweight (BMI >25 kg/m2), 300 million of whom are clinically obese (BMI >30 kg/m2). In the United States, 65% of adults are overweight, and 32.2% of them are obese, a prevalence that has doubled over 20 years. In industrialized countries, obesity rates have tripled, coinciding with adoption of a Western …

Commencement Program 2010, Loma Linda University

Commencement Programs

CONTENTS

1 | Message from the President

3 | 2010 Events of Commencement

4 | The Academic Procession

6 | Significance of Academic Regalia

8 | The Good Samaritan

9 | University History Highlights

11 | Loma Linda University Song - "Healing Love"

12 | The Speakers

22 | The University Honorees

36 | The School Honorees

59 | The Programs

• School of Medicine, 60
• School of Pharmacy, 77
• School of Dentistry, 83
• School of Science and Technology and School of Religion, 99
• School of Nursing, 112
• School of Allied Health Professions - Physical Therapy, 121
• School of Allied Health …

Minimum Agitation Speed For Solid Suspension And Mixing Time In A Torispherical -Bottomed Pharmaceutical Stirred Tank Under Different Baffling Conditions, Dilanji Bhagya Wijayasekara

Theses

The minimum agitation speed, NS, required to just suspend solid particles dispersed in water was experimentally determined in this work for a glass-lined type of mixing tank provided with a torispherical bottom and agitated with a retreat-blade impeller under different baffling configurations. Ns for the same tank but equipped with a different agitation system, namely an axial impeller, was also experimentally determined for the purpose of comparing of performances of the two systems. The effect of impeller off- bottom clearance and the vessel's liquid level on the minimum agitation speed were also experimentally studied. Njs, was experimentally determined …

Intravenous Ibuprofen: The First Injectable Product For The Treatment Of Pain And Fever, P Brandon Bookstaver, April D. Miller, Celeste N. Rudisill, Leann B. Norris

Faculty Publications

This paper reviews the current data on the use of the first approved intravenous ibuprofen product for the management of post-operative pain and fever in the United States. The management of acute and post-operative pain and fever with nonsteroidal anti-inflammatory agents (NSAIDs) is well documented. A search in Medline and International Pharmaceutical Abstracts of articles until the end of November 2009 and references of all citations were conducted. Available manufacturer data on file were also analyzed for this report. Several randomized controlled studies have demonstrated the opioid-sparing and analgesic effects of 400 and 800 mg doses of intravenous ibuprofen in …

Inhibition Of Abcb1 (Mdr1) Expression By An Sirna Nanoparticulate Delivery System To Overcome Drug Resistance In Osteosarcoma, Michiro Susa, Arun K. Iyer, Keinosuke Ryu, Edwin Choy, Francis J. Hornicek, Henry Mankin, Lara Milane, Mansoor M. Amiji, Zhenfeng Duan

Pharmaceutical Sciences Faculty Publications

Background: The use of neo-adjuvant chemotherapy in treating osteosarcoma has improved patients’ average 5 year survival rate from 20% to 70% in the past 30 years. However, for patients who progress after chemotherapy, its effectiveness diminishes due to the emergence of multi-drug resistance (MDR) after prolonged therapy.

Methodology/Principal Findings: In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure resulting from MDR, we designed and evaluated a novel drug delivery system for MDR1 siRNA delivery. Novel biocompatible, lipid-modified dextran-based polymeric nanoparticles were used as the platform for MDR1 siRNA delivery; and the efficacy …

Reduction Of Sympathetic Activity Via Adrenal-Targeted Grk2 Gene Deletion Attenuates Heart Failure Progression And Improves Cardiac Function After Myocardial Infarction., Anastasios Lymperopoulos, Giuseppe Rengo, Erhe Gao, Steven N. Ebert, Gerald W. Dorn, Walter J. Koch

Department of Medicine Faculty Papers

Chronic heart failure (HF) is characterized by sympathetic overactivity and enhanced circulating catecholamines (CAs), which significantly increase HF morbidity and mortality. We recently reported that adrenal G protein-coupled receptor kinase 2 (GRK2) is up-regulated in chronic HF, leading to enhanced CA release via desensitization/down-regulation of the chromaffin cell alpha(2)-adrenergic receptors that normally inhibit CA secretion. We also showed that adrenal GRK2 inhibition decreases circulating CAs and improves cardiac inotropic reserve and function. Herein, we hypothesized that adrenal-targeted GRK2 gene deletion before the onset of HF might be beneficial by reducing sympathetic activation. To specifically delete GRK2 in the chromaffin cells …

Proteomics Reveals A Core Molecular Response Of Pseudomonas Putida F1 To Acute Chromate Challenge, D. K. Thompson, K. Chourey, G. S. Wickham, S. B. Thieman, N. C. Verberkmoes, B. Zhang, A. T. Mccarthy, M. A. Rudisil, M. Shah, R. L. Hettich

Pharmaceutical Sciences

No abstract provided.

Undue Pharmaceutical Influence On Psychiatric Practice, Lisa Cosgrove, Harold J. Bursztajn

Counseling, School Psychology & Sport Faculty Publication Series

Within the past few years, increasing concerns have arisen about the ways in which corporate sponsorship of clinical trials and continuing medical education activities may bias the information that is published and disseminated about the benefits and risks of medications. Questions have also been raised about the extent of industry influence on the American Psychiatric Association’s diagnostic and treatment guidelines—namely, its DSM and Clinical Practice Guidelines.

Organophosphorus Pesticides Decrease M2 Muscarinic Receptor Function In Guinea Pig Airway Nerves Via Indirect Mechanisms, Becky J. Proskocil, Donald A. Bruun, Charles M. Thompson, Allison D. Fryer, Pamela J. Lein

Biomedical and Pharmaceutical Sciences Faculty Publications

Background: Epidemiological studies link organophosphorus pesticide (OP) exposures to asthma, and we have shown that the OPs chlorpyrifos, diazinon and parathion cause airway hyperreactivity in guinea pigs 24 hr after a single subcutaneous injection. OP-induced airway hyperreactivity involves M2 muscarinic receptor dysfunction on airway nerves independent of acetylcholinesterase (AChE) inhibition, but how OPs inhibit neuronal M2 receptors in airways is not known. In the central nervous system, OPs interact directly with neurons to alter muscarinic receptor function or expression; therefore, in this study we tested whether the OP parathion or its oxon metabolite, paraoxon, might decrease M2 receptor function on …

Pharmaceutical Marketing: A Comparison Of Different Markets, Paul Sherlock

Dissertations

No abstract provided.

Angiotensin-Converting Enzyme 2: A New Target For Neurogenic Hypertension, Yumei Feng, Huijing Xia, Robson A. Santos, Robert Speth, Eric Lazartigues

HPD Articles

Overactivity of the renin-angiotensin system (RAS) is involved in the pathogenesis of hypertension, and an overactive brain RAS has been highlighted in several genetic and experimental models. Until now, angiotensin II (Ang II) was thought to be the main effector of this system, and the angiotensin-converting enzyme (ACE)-Ang II-Ang II type 1 receptor axis was the main target for antihypertensive therapies. A new member of the RAS, ACE2 (angiotensin-converting enzyme type 2), has been identified in organs and tissues related to cardiovascular function (e.g. heart, kidney and blood vessels) and appears to be part of a counter-regulatory pathway to buffer …

Tamoxifen: Mechanisms Of Resistance, Cyrus Mccoy Adams

Theses and Dissertations (ETD)

The role of estrogen in breast cancer has been recognized for decades. The selective estrogen receptor modulator tamoxifen was the first targeted therapy for the treatment of breast cancer. It was also the first drug approved by the FDA for the reduction of breast cancer risk. While tamoxifen has extended the lives of countless patients with breast cancer, resistance to tamoxifen remains a significant clinical problem. Work over the last two decades has greatly enhanced our understanding of the molecular mechanisms by which breast cancer cells may become resistant to tamoxifen treatment. Here I review our current understanding of the …

The Design And Synthesis Of Novel Antimicrobial Agents For Use In The Battle Against Bacterial Resistance, Joshua Randal Brown

Theses and Dissertations (ETD)

There is an ever increasing need to develop new antimicrobial agents with novel mechanisms of action. These new agents will help to combat the steady rise of antibiotic-resistant bacteria which are becoming more and more difficult to treat due to the dwindling number of antibiotics available to treat such organisms. This body of work brings to light the many ways in which medicinal chemistry plays a vital role in the discovery of novel antimicrobial agents. Chapter 1 is an introduction into antimicrobial agents. It provides a brief history of the discovery of antimicrobial agents, and delves into reasons why new …

Transcriptional Regulation Of Azole Antifungal Resistance And Tolerance In Candida Glabrata, Kelly E. Caudle

Theses and Dissertations (ETD)

Azole antifungal resistance has emerged as a significant problem in the management of infections caused by fungi including Candida species. In recent years, Candida glabrata has become the second most common cause of mucosal and invasive fungal infections in humans second to Candida albicans. Not only are systemic C. glabrata infections characterized by high mortality rates, treatment failures to the azole class of antifungals, the most widely used antifungal for treatment of Candida infections, have been reported. Contributing to this problem, C. glabrata exhibits intrinsic reduced susceptibility to the azole antifungals, and the development of high-level azole resistance …

Population Pharmacokinetics Of Therapeutic Monoclonal Antibodies: Examples And Estimation Method Performance Differences, Nathanael Le Dirks

Theses and Dissertations (ETD)

Over the past two decades, there has been an increase in the research and development and therapeutic application of monoclonal antibodies (mAbs). An application of pharmacokinetic (PK) and pharmacodynamic concepts that has likely contributed to the success of the pre-clinical and clinical drug development of therapeutic mAbs is population PK, which attempts to quantify the typical disposition characteristics and sources of PK variability (such as between-subject, within-subject, and inter-occasion variability) within study populations. Population PK also attempts to identify and quantify the impact of covariates on systemic drug exposure and assess their potential implications for clinical dosing. The general theme …

Synthesis Of Novel Cannabinoid Ligands And Their Use As Anti-Glioma And Anti-Inflammatory Agents, Steven Neal Gurley

Theses and Dissertations (ETD)

Following the discovery of the cannabinoid receptors, research in the field of cannabinoids has grown exponentially over the last two decades. Cannabinoids have been shown to have tremendous therapeutic potential in the treatment of several pathological conditions ranging from inflammation to asthma, multiple sclerosis, Parkinson’s disease, epilepsy, glaucoma, septic shock, hemorrhagic shock, and cancer. Our research has focused on two major conditions for which cannabinoids hold great promise for drug development, namely, cancer and inflammation.

Our focus in the field of cancer has been on the devastatingly lethal brain tumor glioblastoma multiforme. Due to the high expression of the CB2 …

Tdiscovery And Development Of Novel Therapeutic Agents For Advanced Melanoma, Zhao Wang

Theses and Dissertations (ETD)

Malignant melanoma is the most dangerous form of skin cancer and accounts for about 75% of skin cancer deaths. Once diagnosed at the metastatic stage, it has a very poor prognosis with a median survival rate of 6 months and a 5-year survival rate of less than 5%. In addition, melanoma has become an important public health hazard owing to its rising incidence, which has been well documented over the past 50 years. Currently there is no effective way to treat melanoma. It is highly resistant to existing chemotherapy, radiotherapy, and immunotherapy. Over the past 30 years, only two drugs …

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 …

Library Synthesis Of Anticancer And Antibacterial Agents Via Azide Chemistry, Jianjun Zhang

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Various anticancer and antibacterial agents have been synthesized via azide chemistry by taking advantage of carbohydrate. Starting from the synthesis of 14 glycosyl azides, a library of carbohydrate-oxazolidinone conjugates and a library of carbohydrate-cyclopamine conjugates with biological interests were synthesized based on a highly efficient "click reaction" assisted by sonication. Some of the conjugates have improved solubility and enhanced anticancer activity.

A library of neomycin B derivatives with various modifications at the 5" position has been synthesized. Two leads exhibit prominent activity against both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Antibacterial activities were measured when combined with other …