Medicine and Health Sciences Commons^™

Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors, Bruno Ramos-Molina, Adam N. Lick, Amir Nasrolahi Shirazi, Donghoon Oh, Rakesh Tiwari, Naglaa Salem El-Sayed, Keykavous Parang, Iris Lindberg

Pharmacy Faculty Articles and Research

Cationic cell-penetrating peptides have been widely used to enhance the intracellular delivery of various types of cargoes, such as drugs and proteins. These reagents are chemically similar to the multi-basic peptides that are known to be potent proprotein convertase inhibitors. Here, we report that both HIV-1 TAT47-57 peptide and the Chariot reagent are micromolar inhibitors of furin activity in vitro. In agreement, HIV-1 TAT47-57 reduced HT1080 cell migration, thought to be mediated by proprotein convertases, by 25%. In addition, cyclic polyarginine peptides containing hydrophobic moieties which have been previously used as transfection reagents also exhibited potent furin inhibition in vitro …

Effects Of Pringle Maneuver And Partial Hepatectomy On The Pharmacokinetics And Blood–Brain Barrier Permeability Of Sodium Fluorescein In Rats, Mohammad K. Miah, Imam H. Shaik, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

Liver diseases are known to affect the function of remote organs. The aim of the present study was to investigate the effects of Pringle maneuver, which results in hepatic ischemia–reperfusion (IR) injury, and partial hepatectomy (Hx) on the pharmacokinetics and brain distribution of sodium fluorescein (FL), which is a widely used marker of blood–brain barrier (BBB) permeability. Rats were subjected to Pringle maneuver (total hepatic ischemia) for 20 min with (HxIR) or without (IR) 70% hepatectomy. Sham-operated animals underwent laparotomy only. After 15 min or 8 h of reperfusion, a single 25-mg/kg dose of FL was injected intravenously and serial …

Cronobacter Sakazakii Bacteremia In A 76-Year-Old Woman: A Case Report, Amy Y. Kang, Nancy Garcia, Bhanu Sud, Lee Nguyen

Pharmacy Faculty Articles and Research

Cronobacter sakazakii, commonly found in contaminated infant formula and thereby causes infantile bacteremia, is rarely associated with adult bacteremia. We present the tenth case of C. sakazakii bacteremia in adults. The patient is a 76-year-old woman who resides in a skilled nursing facility and presents with risk factors including bullous pemphigoid, Type II diabetes mellitus, hypertension, hyperlipidemia, chronic kidney disease, and anemia. The therapy was started with intravenous ciprofloxacin and vancomycinempirically. After consultation with an Infectious Diseases specialist, ciprofloxacin and vancomycin was replaced with meropenem based on the patient’s extensive bullous lesions, history of ESBL infections, and possible pneumonia. Later, …

Protein Composition And Movements Of Membrane Swellings Associated With Primary Cilia, Ashraf M. Mohieldin, Hanan S. Haymour, Shao T. Lo, Wissam A. Aboualaiwi, Kimberly F. Atkinson, Christopher J. Ward, Min Gao, Oliver Wessely, Surya M. Nauli

Pharmacy Faculty Articles and Research

Dysfunction of many ciliary proteins has been linked to a list of diseases, from cystic kidney to obesity and from hypertension to mental retardation. We previously proposed that primary cilia are unique communication organelles that function as microsensory compartments that house mechanosensory molecules. Here we report that primary cilia exhibit membrane swellings, which based on their unique ultrastructure and motility, could be mechanically regulated by fluid-shear stress. Together with the ultrastructure analysis of the bulb, which contains monosialodihexosylganglioside (GM3), our results show that ciliary membrane swelling has a distinctive set of functional proteins, including GM3 synthase (GM3S), bicaudal-c1 (Bicc1) and …

The Cell's Antenna And Bending With The Flow, Surya M. Nauli, Kimberly F. Atkinson, Sarmed H. Kathem

Pharmacy Faculty Articles and Research

Polycystic kidney disease (PKD) is the most common life-threatening genetic disease worldwide – affecting about 12.5 million people. Patients with the condition have multiple fluid-filled cysts in their kidneys that lead to a massive enlargement of the organ and gradual worsening of its function, as well as complete failure in many cases. The lack of available treatment means patients may eventually require regular dialysis or a kidney transplant.

Compliance To The Consort Statement On Participant Flow Diagrams In Infectious Disease Randomized Clinical Trials, Onyeka P. Godwin, Brandon Dyson, Paul S. Lee, Soon Park, Euni Lee

Pharmacy Faculty Articles and Research

Background: The Consolidated Standard of Reporting Trials (CONSORT) Guidelines were developed to support adequate reporting of randomized controlled trials (RCTs).

Method: A systematic review was conducted including RCTs of infectious diseases published in the top general medical and infectious disease journals in 2010. The level of compliance to flow diagram and its association with the CONSORT endorsement by the journals were evaluated.

Results: A total of 67 studies were included in the analysis and a half of the studies were HIV/AIDS RCTs. About 78% of the studies included the flow diagram and 66% of the studies described …

Dopaminergic Signaling Within The Primary Cilia In The Renovascular System, Kimberly F. Atkinson, Samred H. Kathem, Xingjian Jin, Brian S. Muntean, Wissam A. Aboualaiwi, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Activation of dopamine receptor type-5 (DR5) has been known to reduce systemic blood pressure, most likely by increasing renal vasodilation and enhancing natriuresis in the kidney. However, the mechanism of DR5 in natriuresis and vasodilation was not clearly known. We have previously shown that DR5 is localized to primary cilia of proximal renal epithelial and vascular endothelial cells. We here show that selective activation of DR5 specifically induces calcium influx only in the primary cilia, whereas non-selective activation of dopamine receptor induces calcium fluxes in both cilioplasm and cytoplasm. Cilia-independent signaling induced by thrombin only shows calcium signaling within cytoplasm. …

A Pharmacist’S Role In The Prevention And Management Of Perioperative Atrial Fibrillation And Flutter, Amanda Harmon, Bethany Smith, Laura Tsu

Pharmacy Faculty Articles and Research

This home-study CPE has been developed to educate pharmacists about recently published guidelines for perioperative atrial fibrillation and flutter management and prevention, and discuss the role a pharmacist can have in the care of these patients.

Comparing The 2013 Acc/Aha & 2014 Nla Dyslipidemia Guidelines And Their Impact On Clinical Decision Making, Alexander Forbes, Kevin Grimes, Jocelyn York, Laura Tsu

Pharmacy Faculty Articles and Research

This home-study CPE activity has been developed to educate pharmacists on the similarities and differences between the 2014 NLA Recommendations for Dyslipidemia Management and the 2013 ACC/AHA Guidelines for Treatment of Blood Cholesterol.

Kaposi Sarcoma Herpesvirus Induces Ho-1 During De Novo Infection Of Endothelial Cells Via Viral Mirna-Dependent And -Independent Mechanisms, Sara Botto, Jennifer Totonchy, Jean K. Gustin, Ashlee V. Moses

Pharmacy Faculty Articles and Research

Kaposi sarcoma (KS) herpesvirus (KSHV) infection of endothelial cells (EC) is associated with strong induction of heme oxygenase-1 (HO-1), a stress-inducible host gene that encodes the rate-limiting enzyme responsible for heme catabolism. KS is an angioproliferative tumor characterized by the proliferation of KSHV-infected spindle cells, and HO-1 is highly expressed in such cells. HO-1 converts the pro-oxidant, proinflammatory heme molecule into metabolites with antioxidant, antiinflammatory, and proliferative activities. Previously published work has shown that KSHV-infected EC in vitro proliferate in response to free heme in a HO-1-dependent manner, thus implicating virus-enhanced HO-1 activity in KS tumorigenesis. The present study investigated …

Design, Synthesis, Antiviral Activity, And Pre-Formulation Development Of Poly-Larginine- Fatty Acyl Derivatives Of Nucleoside Reverse Transcriptase Inhibitors, Bhanu P. Pemmaraju, Swapnil Malekar, Hitesh K. Agarwal, Rakesh Tiwari, Donghoon Oh, Gustavo F. Doncel, David R. Worthen, Keykavous Parang

Pharmacy Faculty Articles and Research

The objective of this work was to design conjugates of anti-HIV nucleosides conjugated with fatty acids and cell-penetrating poly-L-arginine (polyArg) peptides. Three conjugates of polyArg cell-penetrating peptides with fatty acyl derivatives of alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC) were synthesized. In general, the compounds exhibited anti-HIV activity against X4 and R5 cell-free virus with EC50 values of 1.5–16.6 μM. FLT-CO-(CH2)12-CO-(Arg)7 exhibited EC50 values of 2.9 μM and 3.1 μM against X4 and R5 cell-free virus, respectively. The FLT conjugate was selected for further preformulation studies by determination of solution state degradation and lipid solubility. The compound was found to …

Drug-Induced Cardiotoxicity Of Oncological Agents: Monitoring Parameters, Prevention, And Future Chemotherapy, Sarah Nguyen, Mary Nguyen, Laura Tsu

Pharmacy Faculty Articles and Research

The goal of this article is to educate pharmacists of the impact of cardiotoxicity on chemotherapy regimens including key cancer agents, monitoring parameters, prevention, and the future of chemotherapy.