Pharmacy and Pharmaceutical Sciences Commons^™

Lesion Of Cholinergic Neurons In Nucleus Basalis Enhances Response To General Anesthetics, Leung L. Stan

Physiology and Pharmacology Publications

Acetylcholine in the brain has been associated with consciousness and general anesthesia effects. We tested the hypothesis that the integrity of the nucleus basalis magnocellularis (NBM) affects the response to general anesthetics. Cholinergic neurons in NBM were selectively lesioned by bilateral infusion of 192IgG-saporin in adult, male Long–Evans rats, and control rats were infused with saline. Depletion of choline-acetyltransferase (ChAT)-immunoreactive cells in the NBM and decrease in optical density of acetylcholinesterase (AChE) staining in the frontal and visual cortices confirmed a significant decrease in NBM cholinergic neurons in lesioned as compared to control rats. AChE staining in the hippocampus and …

Biopharmaceutic And Pharmacokinetic Evaluation Of Hesperidin And Hesperetin For Ocular Delivery, Ramesh Srirangam

Electronic Theses and Dissertations

The bioflavonoid hesperidin and its aglycone hesperetin are promising candidates for the treatment of diabetic retinopathy and diabetic macular edema because of their pharmacological properties. The objective of this project was to characterize the biopharmaceutic and pharmacokinetic characteristics of hesperidin and hesperetin for ocular delivery, especially with respect to the distribution of these compounds to the posterior segment of the eye. Hesperidin and hesperetin were found to be water insoluble compounds. Although they demonstrated good permeability across the ocular tissues, hesperetin's permeability was found to be higher than that of hesperidin. Hesperidin demonstrated symmetrical transcorneal and transretinal permeation whereas hesperetin …

Facilitating Regulatory Approval Of Multipurpose Prevention Technologies For Sexual And Reproductive Health, Martha Brady

HIV and AIDS

This brief describes multipurpose prevention technologies (MPTs) that address women's sexual and reproductive health (SRH) needs, and how to go about facilitating regulatory approval of this technology. It outlines a strategic framework to examine current regulatory guidance, as well a product development pathway to bring MPTs to market.

Evaluation Of Vancomycin Dosing And Corresponding Drug Concentrations In Pediatric Patients, Lauren Maurer Pharmd, Jenny Boucher Pharmd, Bcps, Ejd

Department of Pharmacy

No abstract provided.

The Effects Of Laropiprant, A Selective Prostaglandin D₂ Receptor 1 Antagonist, On The Antiplatelet Activity Of Clopidogrel Or Aspirin., Aimee Dallob, Wen-Lin Luo, Julie Mabalot Luk, Lisa Ratcliffe, Amy O Johnson-Levonas, Jules I Schwartz, Victor Dishy, Walter K. Kraft, Jan N De Hoon, Anne Van Hecken, Inge De Lepeleire, Waldemar Radziszewski, John A Wagner, Eseng Lai

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Laropiprant (LRPT) is being developed in combination with Merck's extended-release niacin (ERN) formulation for the treatment of dyslipidemia. LRPT, an antagonist of the prostaglandin PGD₂ receptor DP1, reduces flushing symptoms associated with ERN. LRPT also has affinity for the thromboxane A₂ receptor TP (approximately 190-fold less potent at TP compared with DP1). Aspirin and clopidogrel are two frequently used anti-clotting agents with different mechanisms of action. Since LRPT may potentially be co-administered with either one of these agents, these studies were conducted to assess the effects of steady-state LRPT on the antiplatelet activity of steady-state clopidogrel or aspirin. Bleeding time …

Antispasmodic And Ca++ Antagonist Potential Of Marrubiin, A Labdane Type Diterpene From Phlomis Bracteosa, Javid Hussain, Riaz Ullah, Arif-Ullah Khan, Fazal Mabood, Mohammad Raza Shah, Ahmed Al-Harrasi, Anwar Gilani

Department of Biological & Biomedical Sciences

A tricyclic labdane type diterpene was isolated for the first time from ethyl acetate soluble part of Phlomis bracteosa. Its structure was confirmed by x-ray which was found to be marrubiin. When studied in isolated rabbit jejunum, marrubiin caused concentration-dependent relaxation of spontaneous and high K+ (80 mM)-induced contractions, like that caused by verapamil, indicating that marrubiin exhibits spasmolytic activity, possibly mediated through Ca++ channel blocking action.

Constructing A Critical Path For Product Development, Commercialization, And Access, Martha Brady

HIV and AIDS

This brief discusses the Council's health technologies development and the product development path from conceptualization to market. It defines the steps in the Critical Path Framework, and examines activities at the preclinical and clinical stage.

Detecting Counterfeit Anti-Malarials Through Comparison Between High-Pressure Liquid Chromatography And Other Methods Of Analysis, Andrea Irby

Theses & Honors Papers

Counterfeit pharmaceuticals are an increasing trend in the world of criminal activity because the business of making fake pharmaceuticals is highly profitable. The scientific community needs to develop clear-cut methods of detection for counterfeit pharmaceuticals because this is an issue that affects human health and because the use of prescription drugs is so prevalent. This study used high-pressure liquid chromatography (HPLC) and fluorescence spectroscopy to produce qualitative and quantitative data about quinine, mefloquine and choloroquine. These were studied because they are common anti-malarial drugs used in developing nations and they are often counterfeited. Tablet mixtures meant to replicate pharmaceutical tablets …

Click Chemistry Inspired One-Pot Synthesis Of 1, 4-Disubstituted 1, 2, 3-Triazoles And Their Src Kinase Inhibitory Activity, Dalip Kumar, V. Buchi Reddy, Anil Kumar, Deendayal Mandal, Rakesh Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Two classes of 1,4-disubstituted 1,2,3-triazoles were synthesized using one-pot reaction of α-tosyloxy ketones/α-halo ketones, sodium azide, and terminal alkynes in the presence of aq. PEG (1:1, v/v) using the click chemistry approach and evaluated for Src kinase inhibitory activity. Structure-activity relationship analysis demonstrated that insertion of C6H5- and 4-CH3C6H4- at position 4 for both classes and less bulkier aromatic group at position 1 in class 1 contribute critically to the modest Src inhibition activity (IC50 = 32-43 µM) of 1,4-disubstituted 1,2,3-triazoles.

Thiazolyl N-Benzyl-Substituted Acetamide Derivatives: Synthesis, Src Kinase Inhibitory And Anticancer Activities, Asal Fallah-Tafti, Alireza Foroumadi, Rakesh Tiwari, Amir Nasrolahi Shirazi, David G. Hangauer, Yahao Bu, Tahmineh Akbarzadeh, Keykavous Parang, Abbas Shafiee

Pharmacy Faculty Articles and Research

KX2-391 (KX-01/Kinex Pharmaceuticals), N-benzyl-2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)acetamide, is a highly selective Src substrate binding site inhibitor. To understand better the role of pyridine ring and N-benzylsubstitution in KX2-391 and establish the structure-activity relationship, a number of N-benzyl substituted (2-morpholinoethoxy)phenyl)thiazol-4-yl)acetamide derivatives containing thiazole instead of pyridine were synthesized and evaluated for Src kinase inhibitory activities. The unsubstituted N-benzyl derivative (8a) showed the inhibition of c-Src kinase with GI50 values of 1.34 μM and 2.30 M in NIH3T3/c-Src527F and SYF/c-Src527F cells, respectively. All the synthesized compounds were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), breast carcinoma (BT-20), and leukemia (CCRF-CEM) cells. …

Postgraduate Year One (Pgy1) Department Of Pharmacy Residency Program, Jessica Price Pharmd, Bcps

Department of Pharmacy

No abstract provided.

Polyethylenimine-Conjugated Gold Nanoparticles: Gene Transfer Potential And Low Toxicity In The Cornea, Ajay Sharma, Ashish Tandon, Jonathan C. K. Tovey, Rangan Gupta, J. David Robertson, Jennifer A. Fortune, Alexander M. Klibanov, John W. Cowden, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

This study examined the gene transfer efficiency and toxicity of 2-kDa polyethylenimine conjugated to gold nanoparticles (PEI2-GNP) in the human cornea in vitro and rabbit cornea in vivo. PEI2-GNP with nitrogen-to-phosphorus (N/P) ratios of up to 180 exhibited significant transgene delivery in the human cornea without altering the viability or phenotype of these cells. Similarly, PEI2-GNP applied to corneal tissues collected after 12 h, 72 h, or 7 days exhibited appreciable gold uptake throughout the rabbit stroma with gradual clearance of GNP over time. Transmission electron microscopy detected GNP in the keratocytes and the extracellular matrix of the rabbit corneas. …

Biophysical Techniques Of Transcutaneous Drug Sampling And Drug Delivery, Srinivasa Murthy Sammeta

Electronic Theses and Dissertations

Monitoring the time course of drug in the skin is critical for determining the frequency and dose of drug administration from safety and efficacy perspectives. Intermittent blood sampling is used as a surrogate for approximating concentration of drugs in the tissues, which leads to blood loss and discomfort to patients. A novel noninvasive technique called “Electroporation and transcutaneous sampling” (ETS) was developed for estimating the drug concentration in the skin extracellular fluid. The application of ETS technique in studying dermatokinetics of cephalexin, ciprofloxacin, and 8-methoxypsoralen was investigated. The results demonstrated the ability of ETS technique in dermatokinetic studies of drugs …

Topiramate: Safety And Efficacy Of Its Use In The Prevention And Treatment Of Migraine, Ginger C. Minton, April D. Miller, P Brandon Bookstaver, Bryan L. Love

Faculty Publications

Migraine headaches are typically episodic in nature and may affect nearly 10% of the population. In addition to treatment, prevention of subsequent episodes or progression to a chronic migraine state is an important therapeutic area. Topiramate is a centrally acting medication approved for both the prevention of seizures and migraine headache. At this time, the exact mechanism of how topiramate assists in migraine prevention is unknown. Several large randomized, controlled trials have aided in establishing topiramate's role in migraine prevention. Despite a favorable pharmacokinetic and adverse effect profile established in clinical trials, several additional studies, case reports and toxicology reports …

Diverse Inflammatory Responses In Transgenic Mouse Models Of Alzheimer's Disease And The Effect Of Immunotherapy On These Responses, Donna M. Wilcock, Qun Zhao, Dave Morgan, Marcia N. Gordon, Angela Everhart, Joan G. Wilson, Jennifer E. Lee, Carol A. Colton

Molecular Pharmacology & Physiology Faculty Publications

While the presence of an inflammatory response in AD (Alzheimer's disease) is well known, the data on inflammation are conflicting, suggesting that inflammation either attenuates pathology, exacerbates it or has no effect. Our goal was to more fully characterize the inflammatory response in APP (amyloid precursor protein) transgenic mice with and without disease progression. In addition, we have examined how anti-Aβ (amyloid β-peptide) immunotherapy alters this inflammatory response. We have used quantitative RT–PCR (reverse transcription–PCR) and protein analysis to measure inflammatory responses ranging from proinflammatory to anti-inflammatory and repair factors in transgenic mice that develop amyloid deposits only …

Design, Synthesis, Biological Evaluation And Metabolic Stability Studies Of Sigma Receptor Ligands, Rohit Bhat

Electronic Theses and Dissertations

Sigma receptors represent a unique family of proteins that includes two subtypes: sigma-1 and sigma-2. Sigma-1 receptors have been implicated in the behavioral and motivational effects of psychostimulants as well as in the pathophysiology of depression and Alzheimer's disease. Sigma-2 receptors are widely expressed on many tumor cells and they are believed to play an important role in tumor cell proliferation. Therefore, sigma receptors are attractive targets for developing pharmaceutical agents directed to the treatment of psychostimulant abuse, cancer, Alzheimer's disease as well as diagnostic agents for cancer and brain imaging. A derivatized 2(3H)-benzothiazolone, (3-(2-(azepan-1-yl)ethyl)-6-propylbenzo[ d]thiazol-2(3H)-one) was reported to have …

Significant Inhibition Of Corneal Scarring In Vivo With Tissue-Selective, Targeted Aav5 Decorin Gene Therapy, Rajiv R. Mohan, Ashish Tandon, Ajay Sharma, John W. Cowden, Jonathan C. K. Tovey

Pharmacy Faculty Articles and Research

PURPOSE. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the stroma with adeno-associated virus serotype 5 (AAV5) inhibits corneal fibrosis in vivo without significant side effects.

METHODS. An in vivo rabbit model of corneal fibrosis was used. Targeted decorin gene therapy was delivered to the rabbit cornea by a single topical application of AAV5 (100 L; 6.5 1012 g/mL) onto the bare stroma for 2 minutes. The levels of corneal fibrosis were determined with stereomicroscopy, slit lamp biomicroscopy, -smooth muscle actin ( SMA), fibronectin, and F-actin immunocytochemistry, and/or immunoblotting. CD11b, F4/80 immunocytochemistry, and TUNEL assay …

Pharmacy-Level Quality Measures And The Consumer: Preferences And Attitudes, Zainab S. Shahpurwala

Electronic Theses and Dissertations

Objectives. To determine the perceptions of consumers toward community pharmacy quality measures and compare their perceptions regarding their pharmacy's overall quality before and after exposure to these measures. To explore the use of evaluative criteria applied by consumers to determine their preference for information related to these measures. Methods. Focus groups were used to refine attributes and levels used in the quantitative phase of the study. An Internet-based survey was administered to a national, online, consumer panel of community pharmacy patrons using maintenance medications. Descriptive statistics, MANOVA and t-tests were used to determine and compare perceptions related to the community …

Pharmacokinetic Evaluation Of A Novel Compound, Sn79, A Putative Sigma-2 Receptor Antagonist, By Intravenous And Oral Administration In Rats, Harsha Vinnakota

Electronic Theses and Dissertations

Considering the alarming rates at which substance drug abuse, especially cocaine, is increasing in today's society, there is a lot of impetus on the development of medications that can effectively help alleviate its toxicity and addiction. The affinity of cocaine to sigma receptors (sigma-1 and sigma-2) rendered the hypothesis that blocking sigma receptors could be a possible mechanism to attenuate cocaine-induced toxicity and addiction. In this view, SN79, a synthetic compound with selectivity to both sigma-1 and sigma-2 receptors garnered our attraction for its use as an antagonist. This dissertation encompasses detailed investigation of SN79 from drug discovery and development …

The Strategic Value Driver Model: A Methodology For Examining Value Drivers For A New Pharmaceutical Product In Diabetes, Sumit Verma

Electronic Theses and Dissertations

Objective. Objective The primary objective of this study was to explore a new methodological framework—Strategic Value Driver Model (SVDM), for examining value drivers for new pharmaceutical inhaled insulin in diabetes. Methods. A cross-sectional, internet-based survey was used to collect a sample of 483 Type 2 diabetic patients via national panel of diabetic patients. The sample had two subgroups—insulin-naïve (52.9%, n=255) and insulin-user (47.1%, n=227) patients. The comparative performance of insulin syringes/vials, insulin pen and inhaled insulin was captured on four product attributes (i.e., safety, convenience, clinical efficacy and cost) after asking the patients to report the importance of these attributes. …