Medicine and Health Sciences Commons^™

Late-Occurring Vancomycin-Associated Acute Kidney Injury In Children Receiving Prolonged Therapy, Chad Knoderer, Allison Gritzman, Kristen Nichols, Amy Wilson

Chad A. Knoderer

Background: Acute kidney injury (AKI) in patients receiving vancomycin has been associated with trough concentrations ≥15 mg/L and longer therapy duration. The objective of this study was to determine the incidence and factors associated with late AKI in children receiving ≥8 days of vancomycin therapy. Methods: Children aged 30 days to 17 years who were admitted to our institution and received intravenous vancomycin for at least 8 days during January to December of 2007 and 2010 and had a suspected or proven gram-positive infection were included. Late AKI was categorized as AKI occurring after the first 7 days of therapy …

Compatibility Of Vancomycin And Oxacillin During Simulated Y-Site Delivery, Hilary Teibel, Chad Knoderer, Kristen Nichols

Chad A. Knoderer

Background: Vancomycin and oxacillin may be used together as empiric coverage in patients with proven or suspected Staphylococcus aureus infections. Though vancomycin hydrochloride 20 mg/mL and oxacillin sodium 160 mg/mL are reported to be compatible via Y-site delivery, Y-site compatibility of commonly used concentrations, vancomycin 10 mg/mL and oxacillin 20 mg/mL, has not yet been reported. Objective: To determine the Y-site compatibility of vancomycin 10 mg/mL and oxacillin 20 mg/mL. Methods: One vancomycin hydrochloride 1 g vial was reconstituted with 10 mL sterile water for injection (SWFI) and diluted with 90 mL 5% dextrose in water (D5W) in an evacuated …

Optimized Antimicrobial Dosing Strategies: A Survey Of Pediatric Hospitals, Chad Knoderer, Kristen Nichols, Elaine Cox

Chad A. Knoderer

Background Extended-interval aminoglycoside (EIAG) and extended- and continuous-infusion β-lactam (EIBL and CIBL) dosing strategies are increasingly used in adults, but pediatric literature is limited. Objective The objective of this study was to describe the use of EIAG, EIBL, and CIBL dosing in pediatric hospitals in the USA. Study Design, Setting, and Participants A national survey of children’s hospitals was conducted. A single practitioner from each target hospital was identified through the Children’s Hospital Association. Practice-based survey questions identified whether hospitals utilize EIAG, EIBL, and CIBL dosing. Main Outcome Measure The main outcome measure was the percentage utilization of the dosing …

Compatibility Of Vancomycin And Oxacillin During Simulated Y-Site Delivery, Hilary Teibel, Chad Knoderer, Kristen Nichols

Kristen R. Nichols

Background: Vancomycin and oxacillin may be used together as empiric coverage in patients with proven or suspected Staphylococcus aureus infections. Though vancomycin hydrochloride 20 mg/mL and oxacillin sodium 160 mg/mL are reported to be compatible via Y-site delivery, Y-site compatibility of commonly used concentrations, vancomycin 10 mg/mL and oxacillin 20 mg/mL, has not yet been reported. Objective: To determine the Y-site compatibility of vancomycin 10 mg/mL and oxacillin 20 mg/mL. Methods: One vancomycin hydrochloride 1 g vial was reconstituted with 10 mL sterile water for injection (SWFI) and diluted with 90 mL 5% dextrose in water (D5W) in an evacuated …

Cd36 And Na/K-Atpase- Α 1 Form A Proinflammatory Signaling Loop In Kidney, David Kennedy, Yiliang Chen, Wenxin Huang, Jamie Viterna, Jiang Liu, Kristen Westfall, Jian Tian, David Bartlett, W.H. Tang, Zijian Xie, Joseph Shapiro, Roy Silverstein

Jiang Liu

Proatherogenic, hyperlipidemic states demonstrate increases in circulating ligands for scavenger receptor CD36 (eg, oxidized low-density lipoprotein [oxLDL]) and the Na/K-ATPase (eg, cardiotonic steroids). These factors increase inflammation, oxidative stress, and progression of chronic kidney disease. We hypothesized that diet-induced obesity and hyperlipidemia potentiate a CD36/Na/K-ATPase–dependent inflammatory paracrine loop between proximal tubule cells (PTCs) and their associated macrophages and thereby facilitate development of chronic inflammation and tubulointerstitial fibrosis. ApoE^-/- and apoE^-/-/cd36^-/- mice were fed a high-fat diet for ≤32 weeks and examined for physiologic and histologic changes in renal function. Compared with apoE^-/-, apoE^{-/- …}

Use Of Medications Of Questionable Benefit In Advanced Dementia, Jennifer Tjia, Becky Briesacher, Daniel Peterson, Qin Liu, Susan Andrade, Susan Mitchell

Jennifer Tjia

IMPORTANCE: Advanced dementia is characterized by severe cognitive impairment and complete functional dependence. Patients' goals of care should guide the prescribing of medication during such terminal illness. Medications that do not promote the primary goal of care should be minimized. OBJECTIVES: To estimate the prevalence of medications with questionable benefit used by nursing home residents with advanced dementia, identify resident- and facility-level characteristics associated with such use, and estimate associated medication expenditures. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of medication use by nursing home residents with advanced dementia using a nationwide long-term care pharmacy database linked to the Minimum Data …

Drug Interactions With Complementary Medicines, Geraldine Moses, Treasure Mcguire

Treasure McGuire

Health professionals are expected to be familiar with common and clinically significant complementary medicine interactions or at least know where to look them up. Knowing the dynamic and kinetic interactions associated with commonly used complementary medicines helps to identify the risk of drug interactions. Although information on complementary medicine interactions is not readily provided by the manufacturers, evidence is available by way of case reports, independent research and web-based resources, which have increased in recent years. Collectively, these data make interactions with complementary medicines largely predictable and therefore preventable.

Ho-1 Upregulation Attenuates Adipocyte Dysfunction, Obesity, And Isoprostane Levels In Mice Fed High Fructose Diets, Zeid Khitan, Mohit Harsh, Komal Sodhi, Joseph Shapiro, Nader Abraham

Nader G. Abraham

Background. Fructose metabolism is an unregulated metabolic pathway and excessive fructose consumption is known to activate ROS.HO-1 is a potent antioxidant gene that plays a key role in decreasing ROS and isoprostanes.We examinedwhether the fructosemediated increase in adipocyte dysfunction involves an increase in isoprostanes and that pharmacological induction ofHO-1would decrease both isoprostane levels and adipogenesis. Methods and Results. We examined the effect of fructose, on adipogenesis in human MSCs in the presence and absence of CoPP, an inducer of HO-1. Fructose increased adipogenesis and the number of large lipid droplets while decreasing the number of small lipid droplets (𝑃 < 0.05). …

Effect Of Green Tea Extract On Cardiac Hypertrophy Following 5/6 Nephrectomy In The Rat, Snigdha Priyadarshi, Brandon Valentine, Chi Han, Olga Fedorova, Alexei Bagrov, Jiang Liu, Sankaridrug Periyasamy, David Kennedy, Deepak Malhorta, Zijian Xie, Joseph Shapiro

Zijian Xie

Background

Left ventricular hypertrophy commonly complicates chronic renal failure. We have observed that at least one pathway of left ventricular hypertrophy appears to involve signaling through reactive oxygen species (ROS). Green tea is a substance that appears to have substantial antioxidant activity, yet is safe and is currently widely used. We, therefore, studied whether green tea supplementation could attenuate the development of left ventricular hypertrophy in an animal model of chronic renal failure.

Methods

Male Sprague-Dawley rats were subjected to sham or remnant kidney surgery and given green tea extract (0.1% and 0.25%) or plain drinking water for the next …

Initial Evidence Of Endothelial Cell Apoptosis As A Mechanism Of Systemic Capillary Leak Syndrome, Ragheb Assaly, Dan Olson, Jeffrey Hammersley, Pan-Sheng Fan, Jiang Liu, Joseph Shapiro, M. Kahaleh

Jiang Liu

Background: Systemic capillary leak syndrome (SCLS) is a rare disorder of unknown etiology that is characterized by acute recurrent attacks of hypovolemic shock commonly following an inflammatory stimulus such as a viral illness. Prophylactic therapy is generally ineffective, and the outcome is frequently fatal. Methods: In order to investigate the cellular mechanisms leading to SCLS, we examined the effects of sera from two patients with active SCLS on microvascular endothelial cell apoptosis in vitro. Apoptosis was determined by morphologic criteria, DNA fragmentation, annexin V stain, and by a quantitative photometric assay. The apoptotic pathway was investigated by Western blot of …

Grp78/Bip Is Involved In Ouabain-Induced Endocytosis Of The Na/K-Atpase In Llc-Pk1 Cells, Riad Kesiry, Jiang Liu

Jiang Liu

We have demonstrated that ouabain causes dose- and time-dependent decreases both in 86Rb+ uptake and plasmalemmal Na/K-ATPase content of LLC-PK1 cells, which is related to ouabain-induced endocytosis of plasmalemmal Na/K-ATPase in LLC-PK1 cells through a clathrin-dependent mechanism. GRP78/BiP is a resident protein of the endoplasmic reticulum (ER) and acts as a molecular chaperone. Recently, several studies have shown that GRP78/BiP is also expressed on the cell surface and forms heterogeneous, high molecular weight complexes with other proteins. To identify the proteins that are possibly involved in ouabain-induced endocytosis of the Na/K-ATPase in LLC-PK1 cells, we separated and identified endosomal proteins …

Effect Of Green Tea Extract On Cardiac Hypertrophy Following 5/6 Nephrectomy In The Rat, Snigdha Priyadarshi, Brandon Valentine, Chi Han, Olga Fedorova, Alexei Bagrov, Jiang Liu, Sankaridrug Periyasamy, David Kennedy, Deepak Malhorta, Zijian Xie, Joseph Shapiro

Jiang Liu

Background

Left ventricular hypertrophy commonly complicates chronic renal failure. We have observed that at least one pathway of left ventricular hypertrophy appears to involve signaling through reactive oxygen species (ROS). Green tea is a substance that appears to have substantial antioxidant activity, yet is safe and is currently widely used. We, therefore, studied whether green tea supplementation could attenuate the development of left ventricular hypertrophy in an animal model of chronic renal failure.

Methods

Male Sprague-Dawley rats were subjected to sham or remnant kidney surgery and given green tea extract (0.1% and 0.25%) or plain drinking water for the next …

Ouabain And Insulin Induce Sodium Pump Endocytosis In Renal Epithelium, Shalini Gupta, Yanling Yan, Deepak Malhotra, Jiang Liu, Zijian Xie, Sonia Najjar, Joseph Shapiro

Jiang Liu

Cardiotonic steroids signaling through the basolateral sodium pump (Na/K-ATPase) have been shown to alter renal salt handling in intact animals. Because the relationship between renal salt handling and blood pressure is a key determinant of hypertension, and patients with insulin resistance are frequently hypertensive, we chose to examine whether there might be competition for resources necessary for receptor-mediated endocytosis. In LLC-PK1 cells, the Na/K-ATPase-α1 and carcinoembryonic antigen cell adhesion molecule 1, a plasma membrane protein that promotes receptor-mediated endocytosis, colocalized in the plasma membranes and translocated to the intracellular region in response to ouabain. Either ouabain or insulin alone caused …

Use Of Atypical Antipsychotics In Nursing Homes And Pharmaceutical Marketing, Camilla Pimentel, Jennifer Donovan, Terry Field, Jerry Gurwitz, Leslie Harrold, Abir Kanaan, Celeste Lemay, Kathleen Mazor, Jennifer Tjia, Becky Briesacher

Jennifer Tjia

OBJECTIVES: To describe the current extent and type of pharmaceutical marketing in nursing homes (NHs) in one state and to provide preliminary evidence for the potential influence of pharmaceutical marketing on the use of atypical antipsychotics in NHs.

DESIGN: Nested mixed-methods, cross-sectional study of NHs in a cluster randomized trial.

SETTING: Forty-one NHs in Connecticut.

PARTICIPANTS: NH administrators, directors of nursing, and medical directors (n = 93, response rate 75.6%).

MEASUREMENTS: Quantitative data, including prescription drug dispensing data (September 2009-August 2010) linked with Nursing Home Compare data (April 2011), were used to determine facility-level prevalence of atypical antipsychotic use, facility-level …

Effects Of Cardiac Glycosides On Sodium Pump Expression And Function In Llc-Pk1 And Mdck Cells, Jiang Liu, Sankaridrug Periyasamy, William Gunning, Olga Fedorova, Alexi Bagrov, Deepak Malhorta, Zijian Xie, Joseph Shapiro

Zijian Xie

Background: The decreases in proximal tubule sodium reabsorption seen with chronic renal failure and volume expansion have been ascribed to circulating digitalis-like substances (DLS). However, the circulating concentrations of DLS do not acutely inhibit the sodium pump to a degree consistent with the observed changes in proximal tubule sodium reabsorption.

Methods: We examined how cell lines that simulated proximal (LLC-PK1) and distal tubule (MDCK) cells responded to acute (30 min) and long-term (up to 12 hours) Na⁺,K⁺-ATPase inhibition with DLS.

Results: In LLC-PK1, but not MDCK cells, low concentrations of ouabain decreased ⁸⁶Rb uptake profoundly …

Ouabain Induces Endocytosis Of Plasmalemmal Na/K-Atpase In Llc-Pk1 Cells By A Clathrin-Dependent Mechanism, Jiang Liu, Riad Kesiry, Sankaridrug Periyasamy, Deppak Malhorta, Zijian Xie, Joseph Shapiro

Zijian Xie

Background: We have demonstrated that ouabain causes dose- and time-dependent decreases in ⁸⁶Rb uptake in porcine proximal tubular (LLC-PK1) cells. The present study addresses the molecular mechanisms involved in this process.

Methods: Studies were performed with cultured LLC-PK1 and Src family kinase deficient (SYF) cells.

Results: We found that 50 nmol/L ouabain applied to the basal, but not apical, aspect for 12 hours caused decreases in the plasmalemmal Na/K-ATPase. This loss of plasmalemmal Na/K-ATPase reverses completely within 12 to 24 hours after removal of ouabain. Ouabain also increased the Na/K-ATPase content in both early and late endosomes, activated phosphatidylinositol …

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

Zijian Xie

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, Jiang Liu, Man Liang, Lijun Liu, Deepak Malhotra, Zijian Xie, Joseph Shapiro

Zijian Xie

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 …

Ouabain And Insulin Induce Sodium Pump Endocytosis In Renal Epithelium, Shalini Gupta, Yanling Yan, Deepak Malhotra, Jiang Liu, Zijian Xie, Sonia Najjar, Joseph Shapiro

Zijian Xie

Cardiotonic steroids signaling through the basolateral sodium pump (Na/K-ATPase) have been shown to alter renal salt handling in intact animals. Because the relationship between renal salt handling and blood pressure is a key determinant of hypertension, and patients with insulin resistance are frequently hypertensive, we chose to examine whether there might be competition for resources necessary for receptor-mediated endocytosis. In LLC-PK1 cells, the Na/K-ATPase-α1 and carcinoembryonic antigen cell adhesion molecule 1, a plasma membrane protein that promotes receptor-mediated endocytosis, colocalized in the plasma membranes and translocated to the intracellular region in response to ouabain. Either ouabain or insulin alone caused …

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

Zijian Xie

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, 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

Zijian Xie

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 ± …

Ouabain Induces Endocytosis Of Plasmalemmal Na/K-Atpase In Llc-Pk1 Cells By A Clathrin-Dependent Mechanism, Jiang Liu, Riad Kesiry, Sankaridrug Periyasamy, Deppak Malhorta, Zijian Xie, Joseph Shapiro

Jiang Liu

Background: We have demonstrated that ouabain causes dose- and time-dependent decreases in ⁸⁶Rb uptake in porcine proximal tubular (LLC-PK1) cells. The present study addresses the molecular mechanisms involved in this process.

Methods: Studies were performed with cultured LLC-PK1 and Src family kinase deficient (SYF) cells.

Results: We found that 50 nmol/L ouabain applied to the basal, but not apical, aspect for 12 hours caused decreases in the plasmalemmal Na/K-ATPase. This loss of plasmalemmal Na/K-ATPase reverses completely within 12 to 24 hours after removal of ouabain. Ouabain also increased the Na/K-ATPase content in both early and late endosomes, activated phosphatidylinositol …

Ouabain-Induced Endocytosis And Signal Transduction Of The Na/K-Atpase, Jiang Liu

Jiang Liu

Na/K-ATPase can function as a signal transducer as well as an energy transducing ion pump. Cardiac glycosides (including ouabain and marinobufagin, MBG) are a new class of steroid hormones. Ouabain-activated signaling pathways lead to the induction of some early response proto-oncogenes, activation of transcription factors, and cardiac hypertrophy. Low concentration of ouabain also induced endocytosis of the Na/K-ATPase and compartmentalization of some signaling molecules (e.g. c-Src, EGFR, and p42/44 MAPKs) into clathrin-coated pits, early and late endosomes. Ouabain-induced endocytosis of the Na/K-ATPase depends on the activation of Src kinase, clathrin-coated pits formation, and caveolin-1 (the major component of caveolae). Moreover, …

Effects Of Cardiac Glycosides On Sodium Pump Expression And Function In Llc-Pk1 And Mdck Cells, Jiang Liu, Sankaridrug Periyasamy, William Gunning, Olga Fedorova, Alexi Bagrov, Deepak Malhorta, Zijian Xie, Joseph Shapiro

Jiang Liu

Background: The decreases in proximal tubule sodium reabsorption seen with chronic renal failure and volume expansion have been ascribed to circulating digitalis-like substances (DLS). However, the circulating concentrations of DLS do not acutely inhibit the sodium pump to a degree consistent with the observed changes in proximal tubule sodium reabsorption.

Methods: We examined how cell lines that simulated proximal (LLC-PK1) and distal tubule (MDCK) cells responded to acute (30 min) and long-term (up to 12 hours) Na⁺,K⁺-ATPase inhibition with DLS.

Results: In LLC-PK1, but not MDCK cells, low concentrations of ouabain decreased ⁸⁶Rb uptake profoundly …

The Sodium Pump And Cardiotonic Steroids-Induced Signal Transduction Protein Kinases And Calcium-Signaling Microdomain In Regulation Of Transporter Trafficking, Jiang Liu

Jiang Liu

The Na/K-ATPase was discovered as an energy transducing ion pump. A major difference between the Na/K-ATPase and other P-type ATPases is its ability to bind a group of chemicals called cardiotonic steroids (CTS). The plant-derived CTS such as digoxin are valuable drugs for the management of cardiac diseases, whereas ouabain and marinobufagenin (MBG) have been identified as a new class of endogenous hormones. Recent studies have demonstrated that the endogenous CTS are important regulators of renal Na+ excretion and blood pressure. The Na/K-ATPase is not only an ion pump, but also an important receptor that can transduce the ligand-like effect …

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, 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 …

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, 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 ± …

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 …