Medicine and Health Sciences Commons^™

Mccrearamycins A-D, Geldanamycin-Derived Cyclopentenone Macrolactams From An Eastern Kentucky Abandoned Coal Mine Microbe, Xiachang Wang, Yinan Zhang, Larissa V. Ponomareva, Qingchao Qiu, Ryan M. Woodcock, Sherif I. Elshahawi, Xiabin Chen, Ziyuan Zhou, Bruce E. Hatcher, James C. Hower, Chang-Guo Zhan, Sean Parkin, Madan K. Kharel, S. Randal Voss, Khaled A. Shaaban, Jon S. Thorson

Center for Pharmaceutical Research and Innovation Faculty Publications

Four cyclopentenone‐containing ansamycin polyketides (mccrearamycins A–D), and six new geldanamycins (Gdms B–G, including new linear and mycothiol conjugates), were characterized as metabolites of Streptomyces sp. AD‐23‐14 isolated from the Rock Creek underground coal mine acid drainage site. Biomimetic chemical conversion studies using both simple synthetic models and Gdm D confirmed that the mccrearamycin cyclopentenone derives from benzilic acid rearrangement of 19‐hydroxy Gdm, and thereby provides a new synthetic derivatization strategy and implicates a potential unique biocatalyst in mccrearamycin cyclopentenone formation. In addition to standard Hsp90α binding and cell line cytotoxicity assays, this study also highlights the first assessment of Hsp90α …

Adverse Events And Treatment Discontinuations Of Antimuscarinics For The Treatment Of Overactive Bladder In Older Adults: A Systematic Review And Meta-Analysis, Scott Martin Vouri, Clark D. Kebodeaux, Paul M. Stranges, Besu F. Teshome

Pharmacy Practice and Science Faculty Publications

Introduction

Antimuscarinics should be used with caution in older adults with overactive bladder (OAB) due to anticholinergic adverse events (AEs). Systematic reviews and meta-analyses (SRMAs) have analyzed safety-related outcomes but have not specified risk in the elderly, the population at highest risk for AEs. The aim of this review is to explore and evaluate AEs and treatment discontinuations in adults 65 or older taking antimuscarinics for OAB.

Methods

Keywords were searched in MEDLINE, EMBASE, SCOPUS, and Cochrane Central Register for Controlled Trials. Randomized controlled trials (RCTs) along with sub-analyses and pooled analyses that compared antimuscarinics to placebo or another antimuscarinic …

Reduction Of Cocaine-Induced Locomotor Effects By Enriched Environment Is Associated With Cell-Specific Accumulation Of Δfosb In Striatal And Cortical Subregions, Audrey Lafragette, Michael T. Bardo, Virginie Lardeux, Marcello Solinas, Nathalie Thiriet

Psychology Faculty Publications

Background: Early exposure to enriched environments has been shown to decrease the locomotor effects induced by repeated injections of cocaine and modify basal and cocaine-induced total protein levels of the transcription factor ΔFosB in the whole striatum of mice. In this study, we aimed at characterizing whether the profile of ΔFosB accumulation induced by enriched environments and cocaine would be similar or different in terms of brain areas and cell type.

Methods: We used mice expressing the eGFP protein in D1 receptor positive (D1R(+)) neurons to determine whether ΔFosB induced by enriched environment or cocaine injections (5×15 mg/kg) would occur …

Efficacy And Tolerability Of Adjunctive Brivaracetam In Patients With Prior Antiepileptic Drug Exposure: A Post-Hoc Study., Ali A. Asadi-Pooya, Michael R. Sperling, Steve Chung, Pavel Klein, Anyzeila Diaz, Sami Elmoufti, Jimmy Schiemann, John Whitesides

Department of Neurology Faculty Papers

Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) for adjunctive treatment of focal (partial-onset) seizures in adults with epilepsy. This post-hoc analysis was conducted to explore the efficacy of adjunctive BRV in patients with prior levetiracetam (LEV) exposure and whether changes in efficacy were related to the similar mechanism of action of these two drugs. Data were pooled from three Phase III studies (NCT00490035; NCT00464269; NCT01261325) of adults with focal seizures taking 1-2 AEDs who received placebo or BRV 50-200mg/day without titration over a 12-week treatment period. Patients taking concomitant LEV …

Quetiapine Misuse And Abuse: Is It An Atypical Paradigm Of Drug Seeking Behavior?, Sean Hyungwoo Kim, Gayoung Lee, Eric Kim, Hyejin Jung, Jongwha Chang

Institute for Pharmaceutical Outcomes and Policy Faculty Publications

Recent case reports in medical literatures suggest that more and more second-generation atypical antipsychotics (AAs) have been prescribed for off-label use; quetiapine (Brand name: Seroquel^®) showed increase in its trend for off-label use. Little is known about the reasons behind this trend, although historical sedative and hypnotic prescription patterns suggest that despite relatively superior safety profiles of quetiapine (especially for movement disorders), it may be used for treating substance abuse disorder. In addition, recent studies have shown a strong potential for misuse and abuse (MUA) of quetiapine beyond Food and Drug Administration-approved indications. This includes drug-seeking behaviors, such …

February 2017, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

Nucleosome Repositioning During Differentiation Of A Human Myeloid Leukemia Cell Line, Vladimir B. Teif, Jan-Philipp Mallm, Tanvi Sharma, David B. Mark Welch, Karsten Rippe, Roland Eils, Jörg Langowski, Ada L. Olins, Donald E. Olins

Pharmaceutical Sciences Faculty Publications

Cell differentiation is associated with changes in chromatin organization and gene expression. In this study, we examine chromatin structure following differentiation of the human myeloid leukemia cell line (HL-60/S4) into granulocytes with retinoic acid (RA) or into macrophage with phorbol ester (TPA). We performed ChIP-seq of histone H3 and its modifications, analyzing changes in nucleosome occupancy, nucleosome repeat length, eu-/heterochromatin redistribution and properties of epichromatin (surface chromatin adjacent to the nuclear envelope). Nucleosome positions changed genome-wide, exhibiting a specific class of alterations involving nucleosome loss in extended (∼1kb) regions, pronounced in enhancers and promoters. Genes that lost nucleosomes at their …

Inhibition Of Cdk8 Mediator Kinase Suppresses Estrogen Dependent Transcription And The Growth Of Estrogen Receptor Positive Breast Cancer, Martina S. Mcdermott, Alexander A. Chumanevich, Chang-Uk Lim, Jiaxin Liang, Mengqian Chen, Serena Altilia, David Oliver, James M. Rae, Michael Shtutman, Hippokratis Kiaris, Balázs Győrffy, Igor Roninson, Eugenia Broude

Faculty Publications

Hormone therapy targeting estrogen receptor (ER) is the principal treatment for ER-positive breast cancers. However, many cancers develop resistance to hormone therapy while retaining ER expression. Identifying new druggable mediators of ER function can help to increase the efficacy of ER-targeting drugs. Cyclin-dependent kinase 8 (CDK8) is a Mediator complex-associated transcriptional regulator with oncogenic activities. Expression of CDK8, its paralog CDK19 and their binding partner Cyclin C are negative prognostic markers in breast cancer. Meta-analysis of transcriptome databases revealed an inverse correlation between CDK8 and ERα expression, suggesting that CDK8 could be functionally associated with ER. We have found that …

Oled Loki As A Catalyst For Tertiary Amine And Hydroxamate Glycosylation, Ryan R. Hughes, Khaled A. Shaaban, Jianjun Zhang, Hongnan Cao, George N. Phillips Jr., Jon S. Thorson

Center for Pharmaceutical Research and Innovation Faculty Publications

We describe the ability of an engineered glycosyltransferase (OleD Loki) to catalyze the N‐glycosylation of tertiary‐amine‐containing drugs and trichostatin hydroxamate glycosyl ester formation. As such, this study highlights the first bacterial model catalyst for tertiary‐amine N‐glycosylation and further expands the substrate scope and synthetic potential of engineered OleDs. In addition, this work could open the door to the discovery of similar capabilities among other permissive bacterial glycosyltransferases.

Mechanisms Of Modulation Of Brain Microvascular Endothelial Cells Function By Thrombin., Eugen Brailoiu, Megan M. Shipsky, Guang Yan, Mary E. Abood, G. Cristina Brailoiu

College of Pharmacy Faculty Papers

Brain microvascular endothelial cells are a critical component of the blood-brain barrier. They form a tight monolayer which is essential for maintaining the brain homeostasis. Blood-derived proteases such as thrombin may enter the brain during pathological conditions like trauma, stroke, and inflammation and further disrupts the permeability of the blood-brain barrier, via incompletely characterized mechanisms. We examined the underlying mechanisms evoked by thrombin in rat brain microvascular endothelial cells (RBMVEC). Our results indicate that thrombin, acting on protease-activated receptor 1 (PAR1) increases cytosolic Ca

Compounds Including Cox Inhibitor Moiety And Enhanced Delivery Of Active Drugs Using Same, Audra Stinchcomb, Kyung Bo Kim, Ragotham Reddy Pinninti, Priyanka Ghosh, Kalpana S. Paudel

Pharmaceutical Sciences Faculty Patents

The presently-disclosed subject matter includes compounds including a cyclooxygenase enzyme inhibitor moiety and a moiety derived from a drug of interest. In some embodiments, the drug of interest is an opioid. In some embodiments, the compound includes a diclofenac moiety and a naltrexone or naltrexol moiety. The compounds allow for enhanced delivery rates across skin.

Methadone And Corrected Qt Prolongation In Pain And Palliative Care Patients: A Case–Control Study, Katherine Juba, Tina M. Khadem, David Hutchinson, Jack Brown

Pharmacy Faculty/Staff Publications

Background: Methadone (ME) is commonly used in pain and palliative care (PPC) patients with refractory pain or intolerable opioid adverse effects (AEs). A unique ME AE is its corrected QT (QTc) interval prolongation risk, but most evidence exists in methadone maintenance therapy patients.

Objective: Our goal was to identify QTc interval prolongation risk factors in PPC patients receiving ME and other medications known to prolong the QTc interval and develop a risk stratification tool.

Design: We performed a case–control study of adult inpatients receiving ME for pain management.

Settings/Subjects: Adult inpatients receiving ME with a QTc >470 msec (males) and …

Prospect Of The Use Of Checkpoint Inhibitors In Hepatocellular Cancer Treatments, Ali Raufi

Internal Medicine

Hepatocellular cancer (HCC) is a very fatal disease due to limited therapeutic options as well as due to its association with underlying chronic liver disease in the majority of cases. The immune evasion in HCC signifies a major barrier to the delivery of effective immunotherapy. Sorafenib is the only Food and Drug Administration-approved drug available with an overall response rate of 2%–3% and overall survival of 2.8 months. Chemotherapy has not been used routinely because of the relative refractoriness of advanced HCC. The introduction of immune checkpoint inhibitors (cytotoxic T-lymphocyte antigen 4, programmed death 1, and programmed death-ligand 1) has …

A Quantitative Lc-Ms/Ms Method For Simultaneous Determination Of Cocaine And Its Metabolites In Whole Blood, Xiabin Chen, Xirong Zheng, Kai Ding, Ziyuan Zhou, Chang-Guo Zhan, Fang Zheng

Molecular Modeling and Biopharmaceutical Center Faculty Publications

As new metabolic pathways of cocaine were recently identified, a high performance liquid chromatography tandem mass spectrometry (LC–MS/MS) method was developed to simultaneously determine cocaine and nine cocaine-related metabolites in whole blood samples. One-step solid phase extraction was used to extract all of the ten compounds and corresponding internal standards from blood samples. All compounds and internal standards extracted were separated on an Atlantis T3 (100 Å, 3 μm, 2.1 mm × 150 mm I.D) column and detected in positive ion and high sensitivity mode with multiple reaction monitoring. This method was validated for its sensitivity, linearity, specificity, accuracy, precision, …

The Molecular Basis Of Talin2'S High Affinity Toward Β1-Integrin, Yaxia Yuan, Liqing Li, Yanyan Zhu, Lei Qi, Latifeh Azizi, Vesa P. Hytönen, Chang-Guo Zhan, Cai Huang

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Talin interacts with β-integrin tails and actin to control integrin activation, thus regulating focal adhesion dynamics and cell migration. There are two talin genes, Tln1 and Tln2, which encode talin1 and talin2, and it is generally believed that talin2 functions redundantly with talin1. However, we show here that talin2 has a higher affinity to β1-integrin tails than talin1. Mutation of talin2 S339 to leucine, which can cause Fifth Finger Camptodactyly, a human genetic disease, completely disrupted its binding to β–integrin tails. Also, substitution of talin1 C336 with Ser enhanced the affinity of talin1, whereas substitution of talin2 S339 with …

Transcriptomes Reflect The Phenotypes Of Undifferentiated, Granulocyte And Macrophage Forms Of Hl-60/S4 Cells, David B. Mark Welch, Anna Jauch, Jörg Langowski, Ada L. Olins, Donald E. Olins

Pharmaceutical Sciences Faculty Publications

To understand the chromatin changes underlying differential gene expression during induced differentiation of human leukemic HL-60/S4 cells, we conducted RNA-Seq analysis on quadruplicate cultures of undifferentiated, granulocytic- and macrophage-differentiated cell forms. More than half of mapped genes exhibited altered transcript levels in the differentiated cell forms. In general, more genes showed increased mRNA levels in the granulocytic form and in the macrophage form, than showed decreased levels. The majority of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in genes that exhibited differential transcript levels after either RA or TPA treatment. Changes in transcript levels for groups …

Building A Pharmaceutical Company From Scratch, Singapore Management University

Perspectives@SMU

Carl Firth built ASLAN Pharmaceuticals thanks to Big Pharma, investment banking…and beer

Assessment Of Childhood Domestic Injuries Among Joint And Nuclear Families Of Karachi, Asif Khaliq, Amreen Rao, Shahroz Siddiqui, Ghulam Mujtaba Nasir

Department of Biological & Biomedical Sciences

To assess the frequencies and factors of domestic injuries among children aged less than 5 years. This is a cross sectional study, in which parents who have child less than 5 years of age were targeted. A total of 246 participants had provided satisfactory information and they were approached by non-probability purposive sampling technique from January 2016 to June 2016. The data was entered in Excel and then imported to SPSS 19.0 for inferential analysis. In this study, 89.8% (n = 221) mothers and 10.2% (n = 25) father who had participated. 52.08% (n = 123) parents were from joint …

The Effect Of Sazetidine-A And Other Nicotinic Ligands On Nicotine Controlled Goal-Tracking In Female And Male Rats, S. Charntikov, A. M. Falco, K. Fink, Linda P. Dwoskin, R. A. Bevins

Pharmaceutical Sciences Faculty Publications

Nicotine is the primary addictive component of tobacco products and its complex stimulus effects are readily discriminated by humans and non-human animals. Previous preclinical research investigating directly the nature of the nicotine stimulus has been limited to male rodents. The current study began to address this significant gap in the literature by training female and male rats to discriminate 0.4 mg/kg nicotine from saline in the discriminated goal-tracking task. In this task, access to sucrose was intermittently available on nicotine session. On saline session, intermixed with nicotine sessions on separate days, sucrose was not available. Both sexes acquired the discrimination …

Nephrotoxicity During Vancomycin Therapy In Combination With Piperacillin-Tazobactam Or Cefepime, Wilbur Cliff Rutter, Jessica N. Cox, Craig A. Martin, Donna R. Burgess, David S. Burgess

Pharmacy Practice and Science Faculty Publications

Recent reports have demonstrated that vancomycin (VAN) may lead to an increase in the incidence of acute kidney injury (AKI) when it is combined with antipseudomonal beta-lactams. This study compared the incidence of AKI associated with VAN plus piperacillin-tazobactam (TZP) or cefepime (FEP). This was a retrospective, matched cohort study that was conducted at an academic medical center between September 2010 and September 2014 and that included adult patients without severe chronic or structural kidney disease, dialysis, pregnancy, cystic fibrosis, or a hospital transfer receiving TZP-VAN or FEP-VAN for at least 48 h. The primary outcome was the difference in …

Obesity: Current And Potential Pharmacotherapeutics And Targets, Vidya Narayanaswami, Linda P. Dwoskin

Pharmaceutical Sciences Faculty Publications

Obesity is a global epidemic that contributes to a number of health complications including cardiovascular disease, type 2 diabetes, cancer and neuropsychiatric disorders. Pharmacotherapeutic strategies to treat obesity are urgently needed. Research over the past two decades has increased substantially our knowledge of central and peripheral mechanisms underlying homeostatic energy balance. Homeostatic mechanisms involve multiple components including neuronal circuits, some originating in hypothalamus and brain stem, as well as peripherally-derived satiety, hunger and adiposity signals that modulate neural activity and regulate eating behavior. Dysregulation of one or more of these homeostatic components results in obesity. Coincident with obesity, reward mechanisms …

Moderating Effects Of Immunosuppressive Medications And Risk Factors For Post-Operative Joint Infection Following Total Joint Arthroplasty In Patients With Rheumatoid Arthritis Or Osteoarthritis, Elizabeth G. Salt, Amanda T. Wiggins, Mary Kay Rayens, Brent J. Morris, David M. Mannino, Andrew Hoellein, Ryan P. Donegan, Leslie J. Crofford

Nursing Faculty Publications

Objective—Inconclusive findings about infection risks, importantly the use of immunosuppressive medications, in patients who have undergone large-joint total joint arthroplasty challenge efforts to provide evidenced-based perioperative total joint arthroplasty recommendations to improve surgical outcomes. Thus, the aim of this study was to describe risk factors for developing a postoperative infection in patients undergoing TJA of a large joint [total hip arthroplasty, total knee arthroplasty, or total shoulder arthroplasty] by identifying clinical and demographic factors, including the use of high risk medications (i.e., prednisone and immunosuppressive medications) and diagnoses (i.e., rheumatoid arthritis [RA], osteoarthritis [OA], gout, obesity, diabetes mellitus), that …

Novel Experimental Method For The Determination Of The Minimum Agitation Speed For Solids Suspension In Flat-Bottomed Stirred Tank Reactors, Shriarjun Shastry

Theses

Knowledge of the minimum agitation speed, Njs, required to suspend finely divided solids in vessels stirred by an impeller is a critical parameter to properly operate industrial tanks in a large number of industrial operations. The most common experimental approach to measure N_js is that of Zwietering’s (Chem. Eng. Sci., 1958, 8, 244-253), consisting of visually inspecting the tank bottom and visually determining the impeller agitation speed at which the solids are observed to rest on the tank bottom for no more than 1-2 seconds before being swept away. This method is quite reliable, but a method …

Analisis Biaya Akibat Sakit Serta Kualitas Hidup Pasien Diabetes Mellitus Tipe 2 Dengan Penyakit Jantung, Lusiani Septika Sari

Jurnal Ekonomi Kesehatan Indonesia

Indonesia is the fourth most deaths due diabetes mellitus and heart disease among south Asia countries. Cost of illness from diabetes mellitus with heart disease is the highest cost if it is compared with combination of diabetes mellitus with other chronic disease. This study with 110 patients as samples is aiming to describing the cost of illness and quality of life of patients with type 2 diabetes mellitus with heart disease in X public hospital. With cross sectional research design, primary data is collected with survey technique that uses structured questionnaire and secondary data is obtained through medical record document …

Strategi Pemasaran Pelayanan Continuous Ambulatory Peritoneal Dialysis Di Klinik Khusus Ginjal X Batam Tahun 2016, Bertha Toha, Vetty Y Ulianty Permanasari

Jurnal Ekonomi Kesehatan Indonesia

Currently only 53% of patients with end-stage renal disease that can access dialysis and mostly get Hemodialysis (HD), whereas the cost to Continous Ambulatory Peritoneal Dialysis (CAPD) cheaper than HD (Ministry of Health, 2016). Services of CAPD in Clinic for Kidney Disease X. Batam began since 2010, but the number of CAPD patients only 3% of the end stage renal disease patients there. The purpose of this study to analyze the Marketing Strategy of Continuous Ambulatory Peritoneal Dialysis Services at the Clinic for Kidney Disease X Batam Year 2016. The design of the study is an analytic descriptive with quantitative …

Analisis Minimisasi Biaya Amlodipin Generik Dan Bermerk Pada Pengobatan Hipertensi Di Rs X Pekanbaru Tahun 2015, Hanny Merliana, Amal Chalik Sjaaf

Jurnal Ekonomi Kesehatan Indonesia

Hypertension in a big challenge in Indonesia, proven by its prevalence that reached 25% in 2013 and conditions that mostly found in primary health care. In addition, hypertension management is considered to be suboptimal despite the availability of effective drugs. Amlodipine is one of anti-hypertensive that is commonly prescribed by X Hospital, Pekan Baru. Therefore, it is important to do cost minimization analysis to compare both generic and branded Amlodipine as an implementation of cost and quality control. This retrospective study involved early and medium stage of hypertensive patients that have at least a month period of treatment from January …

Cost Effectiveness Analysis Between Hemodialysis And Peritoneal Dialysis, Elsa Novelia, Ryan Rachmad Nugraha, Hasbullah Thabrany

Jurnal Ekonomi Kesehatan Indonesia

The number of patients with End Stage Renal Disease (ESRD) in Indonesia is growing. Increasing prevalence of hypertension and diabetes mellitus contributes to higher prevalence of ESRD. The majority of patients (94%) with ESRD are undertaking hemodialysis (HD) at public and private hospitals. However, continuous ambulatory Peritoneal Dialysis (PD) has been prescribed to small portion of patients with ESRD. The aim of this study was to examine the cost effectiveness between HD and PD on ESRD patients. This study compared 78 HD patients at Hospital X in Bogor and 10 PD patients at Hospital Y in Jakarta. Patient’s quality of …

Biaya Satuan Dan Pemulihan Biaya (Cost Recovery Rate) Layanan Pasien Acute Coronary Syndrome Dengan Rawat Inap Di Rumah Sakit X Tahun 2015, Anna Aurelia, Eka Pujiyanti

Jurnal Ekonomi Kesehatan Indonesia

X Hospital is a Class C Hospital in South Jakarta, which experiencing a substantial increased number of patients since the BPJS has implemented the referral system. Acute Coronary Syndrome (ACS) patient is a patient with a medical emergency require intensive treatment in the ICU. The purpose of this study was to analyze the cost for hospitalized ACS patients at X Hospital in 2015 using activity based costing. The study revealed that the unit cost of hospitalized ACS patients at X Hospital in 2015 was Rp 6.083.444,-. The Cost Recovery Rate for patients with fee-for-service was 227.98% and for BPJS patient …

Analisis Implementasi Kebijakan Rujuk Balik Diabetes Melitus Di Puskesmas X Kota Tangerang Selatan, Aries Hamzah, Wahyu Sulistiadi

Jurnal Ekonomi Kesehatan Indonesia

The Increasing of Prevalence of Diabetes Mellitus will increase health expenditure in Universal Health Coverage (JKN). The role of health primary care as the front side in health services on back referral for Diabetes disease becomes very important. The purpose of this study was to determine the effectiveness of policy implementation in Diabetes Mellitus back referral behind PHC X 2014. This study used a qualitative approach to the study design content analysis and triangulation methods. Primary data obtained by in-depth interviews, focus groups, and observations in the field. Secondary data were obtained from policy documents and literature. The results showed …

Improving Medication Use For Project Home Residents In An Urban Setting, Toni Campanella, Pharmd Candidate, Ashley Maister, Pharmd Candidate, Roshni S. Patel, Pharmd, Bcps

College of Pharmacy Posters

Partners:

Project HOME is a non-profit organization in Philadelphia that provides housing, employment opportunities, medical care, and education to those who are homeless or at risk of becoming homeless, including those with a history of serious mental health or substance misuse disorders.

Jefferson College of Pharmacy students are dedicated to transforming the health and well-being of the community. By engaging in innovative opportunities, students are well-positioned to deliver patient-centered care.

APhA-ASP serves as the collective voice of student pharmacists to provide opportunities for professional growth, to improve patient care, and to envision and advance the future of pharmacy.