Medicine and Health Sciences Commons^™

Attenuation Of Na/K-Atpase Mediated Oxidant Amplification With Pnaktide Ameliorates Experimental Uremic Cardiomyopathy, Jiang Liu, Jiang Tian, Muhammad Chaudhry, Kyle Maxwell, Yanling Yan, Xiaoliang Wang, Preeya T. Shah, Asad A. Khawaja, Rebecca Martin, Tylor J. Robinette, Adee El-Hamdani, Michael W. Dodrill, Komal Sodhi, Christopher A. Drummond, Steven T. Haller, David J. Keenedy, Nader G. Abraham, Zijian Xie, Joseph I. Shapiro Md

Komal Sodhi

We have previously reported that the sodium potassium adenosine triphosphatase (Na/K-ATPase) can effect the amplification of reactive oxygen species. In this study, we examined whether attenuation of oxidant stress by antagonism of Na/K-ATPase oxidant amplification might ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy (PNx). PNx induced the development of cardiac morphological and biochemical changes consistent with human uremic cardiomyopathy. Both inhibition of Na/K-ATPase oxidant amplification with pNaKtide and induction of heme oxygenase-1 (HO-1) with cobalt protoporphyrin (CoPP) markedly attenuated the development of phenotypical features of uremic cardiomyopathy. In a reversal study, administration of pNaKtide after the induction of uremic …

The Role Of Na/K-Atpase Signaling In Oxidative Stress Related To Obesity And Cardiovascular Disease, Krithika Srikanthan, Joseph I. Shapiro Md, Komal Sodhi

Komal Sodhi

Na/K-ATPase has been extensively studied for its ion pumping function, but, in the past several decades, has been identified as a scaffolding and signaling protein. Initially it was found that cardiotonic steroids (CTS) mediate signal transduction through the Na/K-ATPase and result in the generation of reactive oxygen species (ROS), which are also capable of initiating the signal cascade. However, in recent years, this Na/K-ATPase/ROS amplification loop has demonstrated significance in oxidative stress related disease states, including obesity, atherosclerosis, heart failure, uremic cardiomyopathy, and hypertension. The discovery of this novel oxidative stress signaling pathway, holds significant therapeutic

Predicting Adverse Outcomes In Chronic Kidney Disease Using Machine Learning Methods: Data From The Modification Of Diet In Renal Disease, Zeid Khitan, Anna P. Shapiro, Preeya T. Shah, Juan R. Sanabria, Prasanna Santhanam, Komal Sodhi, Nader G. Abraham, Joseph I. Shapiro

Komal Sodhi

Background: Understanding factors which predict progression of renal failure is of great interest to clinicians.

Objectives: We examined machine learning methods to predict the composite outcome of death, dialysis or doubling of serum creatinine using the modification of diet in renal disease (MDRD) data set.

Methods: We specifically evaluated a generalized linear model, a support vector machine, a decision tree, a feed-forward neural network and a random forest evaluated within the context of 10 fold validation using the CARET package available within the open source architecture R program.

Results: We found that using clinical parameters available at entry into the …

Reciprocal Effects Of Oxidative Stress On Heme Oxygenase Expression And Activity Contributes To Reno-Vascular Abnormalities In Ec-Sod Knockout Mice, Tomoko Kawakami, Nitin Puri, Komal Sodhi, Lars Bellner, Toru Takahashi, Kiyoshi Morita, Rita Rezzani, Tim D. Oury, Nader G. Abraham

Komal Sodhi

Heme oxygenase (HO) system is one of the key regulators of cellular redox homeostasis which responds to oxidative stress (ROS) via HO-1 induction. However, recent reports have suggested an inhibitory effect of ROS on HO activity. In light of these conflicting reports, this study was designed to evaluate effects of chronic oxidative stress on HO system and its role in contributing towards patho-physiological abnormalities observed in extracellular superoxide dismutase (EC-SOD, SOD3) KO animals. Experiments were performed in WT and EC-SOD(−/−) mice treated with and without HO inducer, cobalt protoporphyrin (CoPP). EC-SOD(−/−) mice exhibited oxidative stress, renal histopathological abnormalities, elevated blood …