Chemicals and Drugs Commons^™

Effective Non-Viral Delivery Of Sirna To Acute Myeloid Leukemia Cells With Lipid-Substituted Polyethylenimines, Breanne Landry

Pharmacy Faculty Articles and Research

Use of small interfering RNA (siRNA) is a promising approach for AML treatment as the siRNA molecule can be designed to specifically target proteins that contribute to aberrant cell proliferation in this disease. However, a clinical-relevant means of delivering siRNA molecules must be developed, as the cellular delivery of siRNA is problematic. Here, we report amphiphilic carriers combining a cationic polymer (2 kDa polyethyleneimine, PEI2) with lipophilic moieties to facilitate intracellular delivery of siRNA to AML cell lines. Complete binding of siRNA by the designed carriers was achieved at a polymer:siRNA ratio of ~0.5 and led to siRNA/polymer complexes of …

Intestinal, Airway, And Cardiovascular Relaxant Activities Of Thymoquinone, Muhammad Nabeel Ghayur, Anwar Hussain Gilani, Luke Jeffrey Janssen

Department of Biological & Biomedical Sciences

Thymoquinone (TQ) is a bioactive component found in many medicinal herbs. In this study, we report the smooth and cardiac muscle relaxant activities of this compound. TQ concentration dependently suppressed spontaneously contracting rabbit jejunum while also relaxed high K+-(80 mM) induced contractions in jejunum and guinea-pig ileum, indicating activity at voltage-operated Ca++ channels (VOCC). Further, TQ displaced Ca++ concentration-response curves, obtained in a Ca++-free environment, to the right, showing blockade of VOCC. Similar activity was observed with verapamil, a standard VOCC blocker. TQ also exhibited nonadrenergic relaxation of agonist-induced contractions in guinea-pig trachea. When tested in fluo-4-loaded mouse lung slices, …

Incentivizing The Utilization Of Pharmacogenomics In Drug Development, Valerie Gutmann Koch

Journal of Health Care Law and Policy

No abstract provided.

Polymers Used In Medicine: Common Types And Benefits Of Drug Delivery Systems, Camille Andrews

Natural Sciences Student Research Presentations

This poster describes the common types and benefits of drug delivery systems.

N-Myristoylglutamic Acid Derivative Of 3′-Fluoro-3′- Deoxythymidine As An Organogel, Bhupender S. Chhikara, Rakesh Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Designing microbicidal gels of anti-HIV drugs for local application to prevent HIV infection is a subject of major interest. 3′-Fluoro-3′-deoxythymidine (FLT), a nucleoside reverse transcriptase inhibitor (NRTI), was conjugated with a N-myristoylglutamate scaffold. The conjugate showed gelation at 1% (w/w) in different organic solvents, such as toluene, dichloromethane, and chloroform. The gels were opaque and stable at room temperature. The results indicate that myristoyl glutamate derivative of FLT can form an organogel. The gel could have potential application as a topical anti-HIV microbicidal agent.

Bsa Nanoparticles For Sirna Delivery: Coating Effects On Nanoparticle Properties, Plasma Protein Adsorption, And In Vitro Sirna Delivery, Haran Yogasundaram, Markian Stephan Bahniuk, Harsh-Deep Singh, Hamidreza Montazeri Aliabadi, Hasan Uludag, Larry David Unsworth

Pharmacy Faculty Articles and Research

Developing vehicles for the delivery of therapeutic molecules, like siRNA, is an area of active research. Nanoparticles composed of bovine serum albumin, stabilized via the adsorption of poly-L-lysine (PLL), have been shown to be potentially inert drug-delivery vehicles. With the primary goal of reducing nonspecific protein adsorption, the effect of using comb-type structures of poly(ethylene glycol) (1 kDa, PEG) units conjugated to PLL (4.2 and 24 kDa) on BSA-NP properties, apparent siRNA release rate, cell viability, and cell uptake were evaluated. PEGylated PLL coatings resulted in NPs with ζ-potentials close to neutral. Incubation with platelet-poor plasma showed the composition of …

Melatonin Membrane Receptors In Peripheral Tissues: Distribution And Functions, Radomir M. Slominski, Russel J. Reiter, Natalia Schlabritz-Loutsevich, Rennolds S. Ostrom, Andrzej T. Slominski

Pharmacy Faculty Articles and Research

Many of melatonin’s actions are mediated through interaction with the G-protein coupled membrane bound melatonin receptors type 1 and type 2 (MT1 and MT2, respectively) or, indirectly with nuclear orphan receptors from the RORα/RZR family. Melatonin also binds to the quinone reductase II enzyme, previously defined the MT3 receptor. Melatonin receptors are widely distributed in the body; herein we summarize their expression and actions in non-neural tissues. Several controversies still exist regarding, for example, whether melatonin binds the RORα/RZR family. Studies of the peripheral distribution of melatonin receptors are important since they are attractive targets for immunomodulation, regulation of endocrine, …

Cytomegalovirus Cc Chemokine Promotes Immune Cell Migration, Jennifer Totonchy, Michael Denton, Craig N. Kreklywich, Takeshi Andoh, Jessica M. Osborn, Daniel Chen, Ilhem Messaoudi, Susan L. Orloff, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Cytomegaloviruses manipulate the host chemokine/receptor axis by altering cellular chemokine expression and by encoding multiple chemokines and chemokine receptors. Similar to human cytomegalovirus (HCMV), rat cytomegalovirus (RCMV) encodes multiple CC chemokine-analogous proteins, including r129 (HCMV UL128 homologue) and r131 (HCMV UL130 and MCMV m129/130 homologues). Although these proteins play a role in CMV entry, their function as chemotactic cytokines remains unknown. In the current study, we examined the role of the RCMV chemokine r129 in promoting cellular migration and in accelerating transplant vascular sclerosis (TVS) in our rat heart transplant model. We determined that r129 protein is released into culture …

Characterization Of Pasteurella Multocida Strains Isolated From Geese, Zsuzsanna Varga, Dmitriy V. Volokhov, Laszlo Stipkovits, Akos Thuma, Boglarka Sellyei, Tibor Magyar

United States Food and Drug Administration: Publications

Phenotypic and genotypic diversity of forty-two Pasteurella multocida isolates from geese were characterized by analysis of their capsular type, Heddleston serotype, biotype, fimbrial gene allele type, comparative outer membrane protein (OMP) electrophoresis patterns, and were analyzed using PCR for the presence of virulence-associated genes (toxA, tbpA, pfhA, hgbA, hgbB, nanH, nanB, fimA, hsf-1, and pmHAS). A sequence comparison of the thdF and rpoB housekeeping genes of twenty representative P. multocida strains from three different OMP groups demonstrated that seventeen strains were closely related phylogenetically to previously published strains of P. multocida subsp. multocida and P. multocida subsp. gallicida, and only …

A Thousand Tiny Pieces: The Federal Circuit’S Fractured Myriad Ruling, Lessons To Be Learned, And The Way Forward, Jonathan R. K. Stroud

IP Theory

No abstract provided.

Does The Use Of Intravenous Zoledronic Acid, In Combination With Chemotherapy Regimens, Arrest The Development And Spread Of Cancer Cells To Increase Disease-Free Survival In Breast Cancer Patients?, Dara Colasurdo

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not “Does the use of intravenous zoledronic acid, in combination with chemotherapy regimens, arrest the development and spread of cancer cells to increase disease-free survival in breast cancer patients.“

STUDY DESIGN: Review of three English language primary randomized controlled trials published between 2009 and 2010.

DATA SOURCES: Randomized controlled trials and open label, randomized, phase 2 trial comparing the use of zoledronic acid in combination with chemotherapy to the use of chemotherapy alone were found using Medline/PubMed and Cochrane Databases

OUTCOMES MEASURED: The outcomes measured were incidence …

Confounding Issues In Estimation Of Patient-Specific Pharmacokinetic Parameters And Dosage Individualization Of Aminoglycosides, Reza Mehvar

Pharmacy Faculty Articles and Research

Aminoglycoside antibiotics are usually administered by multiple short intravenous infusions at fixed intervals. Today, equations reported 35 years ago by Sawchuk and Zaske are still the cornerstone of methods used for determination of patient-specific pharmacokinetic parameters of aminoglycosides and individualization of drug dosage regimens in many clinical settings. Additionally, these methods are included in many clinical pharmacology curricula in pharmacy and other related fields. However, there are a few issues with regard to the application and/or modification of this method in clinical settings, which may result in some confusion among novice clinicians. For example, serum samples collected from different intervals …

Differential Effects Of Acute Amphetamine And Phencyclidine Treatment And Withdrawal From Repeated Amphetamine Or Phencyclidine Treatment On Social Interaction And Social Memory In Rats, Ming Li, Wei He, Rebecca Munro

Department of Psychology: Faculty Publications

Although animal models based on amphetamine (AMPH) or phencyclidine (PCP) treatment have been used extensively to study the neurobiological and behavioral characteristics of schizophrenia, there are conflicting reports regarding their validity in modeling the negative symptoms and cognitive deficits of schizophrenia. The present study examined how acute AMPH or PCP treatment (Experiment 1) and withdrawal from repeated AMPH treatment (Experiment 2) or PCP treatment (Experiment 3) affects social behavior and social recognition memory in male Sprague-Dawley rats. Each subject was tested on two consecutive days. On the first day, the rats were tested four times (5 min/each) at 10-min intervals …

The Effect Of Natural Antioxidants On Conjugated Linoleic Acid Yield During The Photoisomerization Of Soy Oil Linoleic Acid, Camille Schaffner, Andy Proctor

Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences

Dietary conjugated linoleic acid (CLA) is known to be effective in avoiding many obesity related diseases. Conjugated linoleic acid is a product of ruminant fermentation and 3.4 g/day are needed to obtain the clinical benefits. However, it is difficult to obtain sufficient CLA to realize these benefits from a healthy diet containing dairy and beef products, without increasing levels of dietary cholesterol and saturated fat. A 20% CLA soy oil with low saturated fat and no cholesterol has been produced by photoisomerization of linoleic acid in the triacylglyceride oil. Further increasing the CLA yields has been possible by addition of …

Protein Structure Networks, Lesley H. Greene

Chemistry & Biochemistry Faculty Publications

The application of the field of network science to the scientific disciplines of structural biology and biochemistry, have yielded important new insights into the nature and determinants of protein structures, function, dynamics and the folding process. Advancements in further understanding protein relationships through network science have also reshaped the way we view the connectivity of proteins in the protein universe. The canonical hierarchical classification can now be visualized for example, as a protein fold continuum. This review will survey several key advances in the expanding area of research being conducted to study protein structures and folding using network approaches.

Choreographing The Adenylyl Cyclase Signalosome: Sorting Out The Partners And The Steps, Rennolds S. Ostrom, Amy S. Bogard, Robert Gros

Pharmacy Faculty Articles and Research

Adenylyl cyclases are a ubiquitous family of enzymes and are critical regulators of metabolic and cardiovascular function. Multiple isoforms of the enzyme are expressed in a range of tissues. However, for many processes, the adenylyl cyclase isoforms have been thought of as essentially interchangeable, with their impact more dependent on their common actions to increase intracellular cyclic adenosine monophosphate content regardless of the isoform involved. It has long been appreciated that each subfamily of isoforms demonstrate a specific pattern of “upstream” regulation, i.e., specific patterns of ion dependence (e.g., calcium-dependence) and specific patterns of regulation by kinases (protein kinase A …

Kshv Infection Of Endothelial Cells Manipulates Cxcr7-Mediated Signaling: Implications For Kaposi’S Sarcoma Progression And Intervention, Jennifer Totonchy, Lisa Clepper, Janet Douglas, Liron Pantanowitz, Klaus Fruh, Ashlee V. Moses

Pharmacy Faculty Articles and Research

"CXCR7 was recently characterized as an alternative receptor for the chemokine CXCL12/SDF-1, previously thought to bind and signal exclusively through CXCR4.We recently identified CXCR7 as a key cellular factor in the endothelial cell (EC) dysfunction associated with KSHV infection. CXCL12 signaling is critically associated with tumor growth, angiogenesis and metastasis in several diverse tumors and is one of the most studied chemokine/chemokine receptor interactions in cancer systems. The tumorigenic activity of the CXCL12 signaling axis offers an attractive target for therapeutic intervention in multiple cancers including Kaposi’s Sarcoma (KS). However, most of the research to date was based on the …

Hepatic Immunosuppressive Effects Of Systemically- Administered Novel Dextran-Methylprednisolone Prodrugs With Peptide Linkers In Rats, Imam H. Shaik, Hitesh K. Agarwal, Keykavous Parang, Reza Mehvar

Pharmacy Faculty Articles and Research

The hepatic immunosuppressive activities of two novel dextran prodrugs of methylprednisolone (MP) containing one (DMP1) or five (DMP5) amino acids as linkers were studied in rats. At various times (02 weeks) after intravenous administration of single 5 mg/kg (MP equivalent) doses of each prodrug or MP succinate (MPS), livers were isolated and immunologically stimulated ex vivo with lipopolysaccharide. The concentrations of tumor necrosis factor (TNF)-a in the outlet perfusate were then quantitated to assess immune response. Additionally, the concentrations of DMP1, DMP5, and/or MP were measured in the liver. MPS, DMP5, or DMP1 injections caused a maximum of 48.9%, 63.5%, …

Effects Of Methoprene On The Survivorship Of Adult Aedes Mosquitoes: A Strategy Or Inactivating Released Mosquitoes, Peter J. Brabant Iii

Theses and Dissertations--Entomology

Methoprene is a Juvenile Hormone (JH) analogue commonly used for the control of mosquito larvae. When applied to a mosquito breeding site, methoprene enters the haemolymph, where it mimics the function of JH and interferes with normal metamorphosis, resulting in larval mortality. Methoprene is commonly used for the control of larvae and has not been used as an adulticide, due to an absence of acute effects. This study evaluated possible chronic effects caused by the exposure of adult Aedes mosquitoes to methoprene. Methoprene was applied, in both technical grade and the commercially available Altosid®, topically to adults through droplet application …

Probing Molecular Mechanisms Of The Hsp90 Chaperone: Biophysical Modeling Identifies Key Regulators Of Functional Dynamics, Anshuman Dixit, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could …

A Proposal To Test The Effects Of Factor Ecat1 On Pluripotency, From Reprogramming To Differentiation Of Human Somatic Cells, Vritti R. Goel

CMC Senior Theses

The field of stem cell research has been growing more because of the interest in using stem cells to cure diseases and heal injuries. Human embryonic stem cells, because of the controversy surrounding them—and subsequently the difficulties in acquiring samples of the existing aging cell lines—can only be used in limited capacities. While the development of induced pluripotent stem cells in the last decade has allowed the field to progress closer to medical treatments, the low efficiency of reprogramming a somatic cell to a pluripotent state, and the vast molecular and genomic differences between human embryonic stem cells and human …

An Evaluation Of Warfarin Use And 30-Day Hemorrhage In Bariatric Surgery, Amanda M. Curry, Richard Boorse Md, Peter J. Bechtel Md, Cathy Fuhrman Rn, Msn, Cathleen Webber Rn, Mshs, Suzanne L. Smith Mba, Rrt, Tas

Department of Surgery

No abstract provided.

Quantitative Analysis Of Some Important Metals And Metalloids In Tobacco Products By Inductively Coupled Plasma-Mass Spectrometry (Icp-Ms), Syed Ghulam Musharraf, Muhammad Shoaib, Amna Jabbar Siddiqui, Muhammad Najam-Ul-Haq, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background: Large scale usage of tobacco causes a lot of health troubles in human. Various formulations of tobacco are extensively used by the people particularly in developing world. Besides several toxic tobacco constituents some metals and metalloids are also believed to pose health risks. This paper describes inductively coupled plasma-mass spectrometric (ICP-MS) quantification of some important metals and metalloids in various brands of smoked, sniffed, dipped and chewed tobacco products.

Results: A microwave-assisted digestion method was used for sample preparation. The method was validated by analyzing a certified reference material. Percentage relative standard deviation (% R.S.D.) between recovered …

Inhibition Of Protein Translocation At The Endoplasmic Reticulum Promotes Activation Of The Unfolded Protein Response, Craig Mckibbin, Alina Mares, Michela Piacenti, Helen Williams, Peristera Roboti, Marjo Puumalainen, Anna Callan, Karolina Lesiak-Mieczkowska, Stig Linder, Hanna Harant, Stephen High, Sabine Flitsch, Roger Whitehead, Eileithyia Swanton

Research outputs 2012

Selective small-molecule inhibitors represent powerful tools for the dissection of complex biological processes. ESI (eeyarestatin I) is a novel modulator of ER (endoplasmic reticulum) function. In the present study, we show that in addition to acutely inhibiting ERAD (ER-associated degradation), ESI causes production of mislocalized polypeptides that are ubiquitinated and degraded. Unexpectedly, our results suggest that these non-translocated polypeptides promote activation of the UPR (unfolded protein response), and indeed we can recapitulate UPR activation with an alternative and quite distinct inhibitor of ER translocation. These results suggest that the accumulation of non-translocated proteins in the cytosol may represent a novel …

Does The Use Of An Oral Lipase Inhibitor (Orlistat) Increase Appetite?, Sandra Boyd

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: To determine whether or not Orlistat ingested prior to a meal causes an increased appetite response.

STUDY DESIGN: A Review of three randomized controlled trials studies from 2003-2008 that were in the English language.

DATA RESOURCES: Randomized controlled trials comparing the effect of Orlistat on satiety were found using PubMed, OVID, and Cochrane databases.

OUTOMES MEASURED: Outcomes measured in the studies were: sensation of appetite, hunger, fullness, nausea, bloating, heartburn, belching, epigastric burning, and prospective food consumption. Each study measured individual patient responses using a VAS (visual analogue scale). Demarchi et al (2004) used a gastric barostat to measure …

Does Tadalafil Improve Exercise Capacitance In Patients Over 12 Years Old With Pulmonary Hypertension?, Erin Chesnavich

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this systematic review is to determine whether or not the oral Phosphodiesterase inhibitor Tadalafil improves exercise capacitance in those over 12 years with pulmonary hypertension.

Study Design: Review of three primary research materials published in English language in 2009. Data Sources: Randomized, controlled, double blind clinical trials found using PubMed, OVID and COCHRANE databases.

Outcome measured: Trials measured 6-minute walking distance and health related quality of life measurements which included: SF-36 (a measure of self reported health status), and the EQ-5D (a patient reported health related quality of life measure), WHO functional class, clinical worsening, and …

Is Intravenous Ramosetron 0.3 Mg Effective In The Prevention Of Postoperative Nausea And Vomiting In Women Undergoing Gynecologic Surgery?, Keith S. Elsner

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not intravenous ramosetron 0.3 mg is effective in the prevention of postoperative nausea and vomiting (PONV) in women undergoing gynecologic surgery.

STUDY DESIGN: Review of three English language primary research articles published later than 1995.

DATA SOURCES: Randomized, double-blinded, controlled clinical trials comparing intravenous ramosetron to placebo or other control groups were identified using Ovid MEDLINE and Cochrane Library databases.

OUTCOMES MEASURED: Measured outcomes include a complete response to the intervention within the first 24-48 hours, the incidence of postoperative nausea and vomiting, need for rescue antiemetic, …

Is Afrin (Oxymetazoline) A Safe And Effective Drug In Normal, Healthy Adults With Reference To Nasal Congestion And The Nasal Response?, Allie Rubinstein

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not, “Is Afrin (Oxymetazoline) a safe and effective drug in normal, healthy adults with reference to nasal congestion and the nasal response?”

STUDY DESIGN: Review of three English language primary studies published in 1997, 1999, 2003.

DATA SOURCES: Randomized, controlled studies (double-blind, placebo-controlled) testing the efficacy and safeness of Afrin in comparison to a placebo group, were found using the PubMed database.

OUTCOMES MEASURED: Nasal patency, congestion, degree of nasal blockage, and symptoms (quantity, consistency, color of nasal secretions, turbinate size/color) were measured through patient diary card …

Is Fixed-Combination Prostaglandin Analog/Β-Blocker Therapy Safe And More Effective Than Β-Blocker Monotherapy In The Prevention Of Disease Progression In Adults With Open-Angle Glaucoma?, My-Hang Pham

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this selective EBM review is to determine whether fixed-combination prostaglandin analog/β-blocker therapy is safe and more effective than β-blocker monotherapy in the prevention of disease progression in adults with open-angle glaucoma.

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

Data sources: 3 randomized, controlled, double-blind trials comparing fixed-combination prostaglandin analog/β-blocker therapy to β-blocker monotherapy were found using Pubmed, Medline, and Cochrane databases.

Outcome Measured: Disease progression/regression was assessed by post-baseline measurement of IOP during three follow-up visits throughout the trials. The safety profile of each therapy was …

Is Asenapine More Effective Than Other Interventions In The Treatment Of Adult Patients With Bipolar I Disorder?, Mary H. Tsakiris

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Asenapine is more effective than other interventions in the treatment of adult patients with bipolar I disorder.

STUDY DESIGN: Review of three English language primary randomized controlled trial studies published from 2009-2010.

DATA SOURCES: Three randomized controlled trials studying the effectiveness of Asenapine in the treatment of mania in adult patients with bipolar I disorder in comparison to other interventions.

OUTCOME MEASURED: Outcomes measured were reduction in severity of manic symptoms and tolerability of the medication. The severity of manic symptoms was measured using the Young …