Regulation Of Apical Nhe3 Trafficking By Ouabain-Induced Activation Of Basolateral Na/K-Atpase Receptor Complex,
2015
Selected Works
Regulation Of Apical Nhe3 Trafficking By Ouabain-Induced Activation Of Basolateral Na/K-Atpase Receptor Complex, Haiping Cai, Liang Wu, Weikai Qu, Deepak Malhotra, Zijian Xie, Joseph I. Shapiro, Jiang Liu
Jiang Liu
The long-term effects of ouabain on transepithelial Na+ transport involve transcriptional downregulation of apical Na+/H+ exchanger isoform 3 (NHE3). The aim of this study was to determine whether ouabain could acutely regulate NHE3 via a posttranscriptional mechanism in LLC-PK1 cells. We observed that the basolateral, but not apical, application of ouabain for 1 h significantly reduced transepithelial Na+ transport. This effect was not due to changes in the integrity of tight junctions or increases in the intracellular Na+ concentration. Ouabain regulated the trafficking of NHE3 and subsequently inhibited its activity, a process independent of intracellular Na+ concentration. Ouabain-induced NHE3 trafficking …
Cardiac Glycoside Downregulates Nhe3 Activity And Expression In Llc-Pk1 Cells,
2015
Marshall University
Cardiac Glycoside Downregulates Nhe3 Activity And Expression In Llc-Pk1 Cells, Shadi Oweis, Liang Wu, Pawel Kiela, Deepak Malhotra, Fayez Ghishan, Zijian Xie, Joseph Shapiro, Jiang Liu
Jiang Liu
Ouabain, a cardiotonic steroid and a specific inhibitor of the Na+-K+-ATPase, has been shown to significantly inhibit transcellular Na+ transport without altering the intracellular Na+ concentration ([Na+]i) in the epithelial cells derived from the renal proximal tubules. We therefore studied whether ouabain affects the activity and expression of Na_/H_ exchanger isoform 3 (NHE3) representing the major route of apical Na_ reabsorption in LLC-PK1 cells. Chronic basolateral, but not apical, exposure to low-concentration ouabain (50 and 100 nM) did not change [Na+]i but significantly reduced NHE3 activity, NHE3 protein, and mRNA wxpression. Inhibition of c-Src or phosphoinositide 3-kinase (PI3K) with PP2 …
Ouabain-Induced Endocytosis Of The Plasmalemmal Na/K-Atpase In Llc-Pk1 Cells Requires Caveolin-1,
2015
Marshall University
Ouabain-Induced Endocytosis Of The Plasmalemmal Na/K-Atpase In Llc-Pk1 Cells Requires Caveolin-1, Jiang Liu, Man Liang, Lijun Liu, Deepak Malhotra, Zijian Xie, Joseph Shapiro
Jiang Liu
Background: We have demonstrated that ouabain causes dose- and time-dependent decreases in 86Rb uptake in pig renal proximal tubule cell line (LLC-PK1) cells; and ouabain induces endocytosis of plasmalemmal Na/K-ATPase in LLC-PK1 cells in a clathrin-dependent pathway. Our data also suggest a role of endocytosis in both ouabain-induced signal transduction and proximal tubule sodium handling. The present study addresses the molecular mechanisms involved in this process. Methods: Studies were performed with cultured LLC-PK1 and a stable-expressed caveolin-1 knockdown LLC-PK1 cell line by SiRNA method. Results: In wild-type LLC-PK1 cells, depletion of cholesterol by methyl -cyclodextrin reduced ouabain-induced accumulation of Na/K-ATPase …
Intracellular Reactive Oxygen Species Mediate The Linkage Of Na+/K+-Atpase To Hypertrophy And Its Marker Genes In Cardiac Myocytes,
2015
Marshall University
Intracellular Reactive Oxygen Species Mediate The Linkage Of Na+/K+-Atpase To Hypertrophy And Its Marker Genes In Cardiac Myocytes, Joseph I. Shapiro, Amir Askari, Zijian Xie, Peter Kometiani, Jie Li, Jiang Liu
Jiang Liu
We showed before that in cardiac myocytes partial inhibition of Na+/K+-ATPase by nontoxic concentrations of ouabain causes hypertrophy and transcriptional regulations of growth-related marker genes through multiple Ca2+-dependent signal pathways many of which involve Ras and p42/44 mitogen-activated protein kinases. The aim of this work was to explore the roles of intracellular reactive oxygen species (ROS) in these ouabain-initiated pathways. Ouabain caused a rapid generation of ROS within the myocytes that was prevented by preexposure of cells to N-acetylcysteine (NAC) or vitamin E. These antioxidants also blocked or attenuated the following actions of ouabain: inductions of the genes of skeletal …
Ouabain-Stimulated Trafficking Regulation Of The Na/K-Atpase And Nhe3 In Renal Proximal Tubule Cells,
2015
Marshall University
Ouabain-Stimulated Trafficking Regulation Of The Na/K-Atpase And Nhe3 In Renal Proximal Tubule Cells, Yanling Yan, Steven Haller, Anna Shapiro, Nathan Malhotra, Jiang Tian, Zijian Xie, Deepak Malhotra, Joseph Shapiro, Jiang Liu
Jiang Liu
We have demonstrated that ouabain regulates protein trafficking of the Na/K-ATPase a1 subunit and NHE3 (Na/H exchanger, isoform 3) via ouabain-activated Na/K-ATPase signaling in porcine LLC-PK1 cells. To investigate whether this mechanism is species-specific, ouabain-induced regulation of the a1 subunit and NHE3 as well as transcellular 22Na? transport were compared in three renal proximal tubular cell lines (human HK-2, porcine LLC-PK1, and AAC-19 originated from LLC-PK1 in which the pig a1 was replaced by ouabain-resistant rat a1). Ouabain-induced inhibition of transcellular 22Na? transport is due to an ouabain-induced redistribution of the a1 subunit and NHE3. In LLC-PK1 cells, ouabain also …
Salt Loading Induces Redistribution Of The Plasmalemmal Na/K-Atpase In Proximal Tubule Cells,
2015
Marshall University
Salt Loading Induces Redistribution Of The Plasmalemmal Na/K-Atpase In Proximal Tubule Cells, Sankaridrug Periyasamy, Jiang Liu, Feras Tanta, Besher Kabak, Brent Wakefield, Deepak Malhorta, David Kennedy, Alaa Nodoor, Olga Fedorova, William Gunning, Zijian Xie, Alexi Bagrov, Joseph Shapiro
Jiang Liu
Background: We have reported that digitalis-like substances (cardiotonic steroids), including marinobufagenin (MBG), induce endocytosis of the plasmalemmal Na/K-ATPase in LLCPK1 cells. The current report addresses the potential relevance of plasmalemmal Na/K-ATPase redistribution to in vivo salt handling. Methods: Male Sprague-Dawley rats were given 1 week of a high salt (4.0% NaCl) or normal salt (0.4% NaCl) diet. Urinary sodium excretion, as well as MBG excretion, was monitored, and proximal tubules were isolated using a Percoll gradient method. Tubular 86Rb uptake, Na/K-ATPase enzymatic activity, and Na/K-ATPase a1 subunit density were determined. Results: The high salt diet increased urinary sodium (17.8 ± …
Implementing Extended-Infusion Cefepime As Standard Of Care In A Children’S Hospital: A Prospective Descriptive Study,
2015
Butler University
Implementing Extended-Infusion Cefepime As Standard Of Care In A Children’S Hospital: A Prospective Descriptive Study, Kristen R. Nichols, Lauren C. Karmire, Elaine G. Cox, Michael B. Kays, Chad A. Knoderer
Chad A. Knoderer
Background: Extended-infusion cefepime (EIC) has been associated with decreased mortality in adults, but to our knowledge, there are no studies in children. Objective: The objective of this study was to determine the feasibility of implementing EIC as the standard dosing strategy in a pediatric population. Methods: This was a descriptive study of children aged 1 month to 17 years, including patients in the intensive care unit, who received cefepime after admission to a freestanding, tertiary care children’s hospital. Patients were excluded if they were admitted to the neonatal intensive care unit or received cefepime in the outpatient, operating, or emergency …
Acid-Suppressing Agents And Risk For Clostridium Difficile Infection In Pediatric Patients,
2015
Butler University
Acid-Suppressing Agents And Risk For Clostridium Difficile Infection In Pediatric Patients, Katelyn Brown, Chad Knoderer, Kristen Nichols, Ashley Crumby
Chad A. Knoderer
Background. Acid-suppressing agents have been associated with increased Clostridium difficile infection (CDI) in adults. The objective of this study was to evaluate the association of acid-suppressing therapy with the development of CDI in the pediatric population. Methods. This was a retrospective case-control study. Children aged 1 through 17 years with a positive C difficile polymerase chain reaction (PCR) result obtained between June 1, 2008, and June 1, 2012, were randomly matched to a control population selected from patients with negative PCR. Results. A total of 458 children were included. No difference was observed in acid-suppressive therapy prior to PCR in …
Implementing Extended-Infusion Cefepime As Standard Of Care In A Children’S Hospital: A Prospective Descriptive Study,
2015
Butler University
Implementing Extended-Infusion Cefepime As Standard Of Care In A Children’S Hospital: A Prospective Descriptive Study, Kristen R. Nichols, Lauren C. Karmire, Elaine G. Cox, Michael B. Kays, Chad A. Knoderer
Kristen R. Nichols
Background: Extended-infusion cefepime (EIC) has been associated with decreased mortality in adults, but to our knowledge, there are no studies in children. Objective: The objective of this study was to determine the feasibility of implementing EIC as the standard dosing strategy in a pediatric population. Methods: This was a descriptive study of children aged 1 month to 17 years, including patients in the intensive care unit, who received cefepime after admission to a freestanding, tertiary care children’s hospital. Patients were excluded if they were admitted to the neonatal intensive care unit or received cefepime in the outpatient, operating, or emergency …
Acid-Suppressing Agents And Risk For Clostridium Difficile Infection In Pediatric Patients,
2015
Butler University
Acid-Suppressing Agents And Risk For Clostridium Difficile Infection In Pediatric Patients, Katelyn E. Brown, Chad A. Knoderer, Kristen R. Nichols, Ashley S. Crumby
Kristen R. Nichols
Background. Acid-suppressing agents have been associated with increased Clostridium difficile infection (CDI) in adults. The objective of this study was to evaluate the association of acid-suppressing therapy with the development of CDI in the pediatric population. Methods. This was a retrospective case-control study. Children aged 1 through 17 years with a positive C difficile polymerase chain reaction (PCR) result obtained between June 1, 2008, and June 1, 2012, were randomly matched to a control population selected from patients with negative PCR. Results. A total of 458 children were included. No difference was observed in acid-suppressive therapy prior to PCR in …
Canagliflozin, A New Sodium-Glucose Co-Transporter 2 Inhibitor, In The Treatment Of Diabetes,
2015
Butler University
Canagliflozin, A New Sodium-Glucose Co-Transporter 2 Inhibitor, In The Treatment Of Diabetes, Sarah A. Nisly, Denise M. Kolanczyk, Alison M. Walton
Alison M. Walton
Purpose. The published evidence on the pharmacology, pharmacodynamics, pharmacokinetics, safety, and efficacy of a promising investigational agent for managing type 2 diabetes is evaluated. Summary. Canagliflozin belongs to a class of agents—the sodium–glucose cotransporter 2 (SGLT2) inhibitors—whose novel mechanism of action offers potential advantages over other antihyperglycemic agents, including a relatively low hypoglycemia risk and weight loss-promoting effects. Canagliflozin has dose-dependent pharmacokinetics, and research in laboratory animals demonstrated high oral bioavailability (85%) and rapid effects in lowering glycosylated hemoglobin (HbA1c) values. In four early-stage clinical trials involving a total of over 500 patients, the use of canagliflozin for varying periods …
Teratogen Use In Women Of Childbearing Potential: An Intervention Study,
2015
Butler University
Teratogen Use In Women Of Childbearing Potential: An Intervention Study, Karie Morical-Kline, Alison Walton, Tracey Guildenbecher
Alison M. Walton
Purpose: The purpose of this study was to quantify the number of women of childbearing potential who are prescribed angiotensin-converting enzyme inhibitor (ACE inhibitor), angiotensin receptor blocker (ARB), or HMG-coenzyme A reductase inhibitor (statin) and to determine the number of documented teratogenic risk discussions (risk documentation) before and after educational interventions. Methods: The institutional review board–approved retrospective chart review included female patients ages 15 to 45 years who were prescribed an ACE inhibitor, ARB, or statin between January 1, 2007, and March 1, 2009. Exclusion criteria were tubal ligation and hysterectomy. A survey determined physician knowledge of teratogenic risks and …
Pneumonia: Not Getting Vaccinated May Take Your Breath Away,
2015
Harding University College of Pharmacy
Pneumonia: Not Getting Vaccinated May Take Your Breath Away, Rodney Richmond
College of Pharmacy Faculty Research and Publications
No abstract provided.
Pharmacists And Pharmacogenomics: An Evaluation Of Knowledge, Beliefs, Attitudes And Practices,
2015
Arizona State University
Pharmacists And Pharmacogenomics: An Evaluation Of Knowledge, Beliefs, Attitudes And Practices, Laressa Bethishou, Angela Chen, Chrissie Chew, Richard Dang, Courtney Greenber, Rebecca Ashlee Klevens, Vlada Treynker, Andrew Warnock, Melissa Durham, Jeffery A. Goad, Edith Mirzaian
Jeff Goad
"Pharmacogenomics is the term used to describe the rapidly advancing study on how genetic makeup can impact drug therapy. In specialized clinical situations, such as the use of irinotecan in colon cancer or abacavir in HIV infections, it is now possible to identify specific genotypes that correlate strongly with a patient's therapeutic outcome, with implications on both efficacy and side effects. On a broader scale, a systematic review published by the Journal of the American Medical Association on the top 27 adverse reaction-causing drugs found that a majority of the adverse effects have a genetic component, suggesting that an analysis …
Y-Site Compatibility Of Vancomycin And Piperacillin/ Tazobactam At Commonly Utilized Pediatric Concentrations,
2015
Butler University
Y-Site Compatibility Of Vancomycin And Piperacillin/ Tazobactam At Commonly Utilized Pediatric Concentrations, Kristen Nichols, Michael Demarco, Michael Vertin, Chad Knoderer
Chad A. Knoderer
Background: Vancomycin and piperacillin/tazobactam are common empiric antibiotics in hospitalized pediatric patients. Studies evaluating intravenous (IV) compatibility at various concentrations show inconsistent results. Objective: The objective of this study was to determine the Y-site compatibility of vancomycin 10 mg/mL and piperacillin/tazobactam 112.5 mg/mL. Methods: Vancomycin (10 g vial) was reconstituted using sterile water for injection (SWFI) and diluted with 5% dextrose in water (D5W) to a final concentration of 10 mg/mL in an evacuated IV bag. Piperacillin/tazobactam (40.5 g vial) was reconstituted and diluted with SWFI to a final concentration of 112.5 mg/mL (100 mg/mL piperacillin) in an evacuated IV …
Hyperphosphatemia In Pediatric Oncology Patients Receiving Liposomal Amphotericin B,
2015
Butler University
Hyperphosphatemia In Pediatric Oncology Patients Receiving Liposomal Amphotericin B, Chad A. Knoderer, Holly M. Knoderer
Chad A. Knoderer
OBJECTIVE: After transitioning our front-line amphotericin product to the liposomal formulation, we observed an increased incidence of hyperphosphatemia. We aimed to determine the incidence of hyperphosphatemia in children with oncologic disorders receiving an amphotericin B product and to establish whether the incidence varies depending on amphotericin formulation. METHODS: This retrospective review of the medical record was conducted at a tertiary, free standing children’s hospital. Pharmacy data revealed 159 patients receiving an amphotericin product between November 2006 and December 2008. Doses of amphotericin, serum phosphorous, calcium and creatinine concentrations were recorded at daily time points during the 10 days following both …
Continuous Infusion Of Nafcillin For Sternal Osteomyelitis In An Infant After Cardiac Surgery,
2015
Butler University
Continuous Infusion Of Nafcillin For Sternal Osteomyelitis In An Infant After Cardiac Surgery, Chad A. Knoderer, Jennifer L. Morris, Elaine G. Cox
Chad A. Knoderer
We report the use of the continuous infusion of nafcillin for the treatment of an infant who had methicillinsusceptible Staphylococcus aureus sternal osteomyelitis not responsive to traditional nafcillin dosing. The patient was successfully treated with surgical debridement and the continuous infusion of nafcillin. To our knowledge, this is the first report describing the successful use of the continuous infusion of nafcillin to treat an infant who had sternal osteomyelitis after cardiac surgery.
Vancomycin And Gentamicin Pharmacokinetic Alterations In An Adolescent Amputee,
2015
Butler University
Vancomycin And Gentamicin Pharmacokinetic Alterations In An Adolescent Amputee, Kristen R. Nichols, Kari M. Edison, Michelle D. Rosenbaum, Chad A. Knoderer
Chad A. Knoderer
A 14-year-old male with bilateral above-the-knee amputations presented to our hospital for treatment of a skin and soft-tissue infection. We report the experience of vancomycin and gentamicin therapy in this patient. Because these medications require weight-based dosages and pharmacokinetic monitoring of serum levels, it was necessary to obtain peak and trough levels of the two drugs in order to determine the pharmacokinetic differences in this patient compared to those in an adolescent male without amputations. To our knowledge, this is the first report describing pharmacokinetic differences in an adolescent amputee.
Linezolid-Associated Thrombocytopenia In Children With Renal Impairment,
2015
Butler University
Linezolid-Associated Thrombocytopenia In Children With Renal Impairment, Sara Jones, Kristen Nichols, Heather Deyoung, Elaine Cox, Chad Knoderer
Chad A. Knoderer
Impaired renal function has been associated with an increased risk of thrombocytopenia in adults receiving linezolid. Findings from this retrospective cohort demonstrate an association between thrombocytopenia and lower creatinine clearance in children receiving linezolid.
Linezolid-Associated Thrombocytopenia In Children With Renal Impairment,
2015
Butler University
Linezolid-Associated Thrombocytopenia In Children With Renal Impairment, Sara Jones, Kristen Nichols, Heather Deyoung, Elaine Cox, Chad Knoderer
Kristen R. Nichols
Impaired renal function has been associated with an increased risk of thrombocytopenia in adults receiving linezolid. Findings from this retrospective cohort demonstrate an association between thrombocytopenia and lower creatinine clearance in children receiving linezolid.
