Medicine and Health Sciences Commons^™

Role Of Serum Biomarkers In Early Detection Of Non-Alcoholic Steatohepatitis And Fibrosis In West Virginian Children, Komal Sodhi, Lucas Bracero, Andrew S. Feyh, Alexandra Nichols, Krithika Srikanthan, Tariq M. Latif, Deborah L. Preston, Joseph I. Shapiro, Yoram Elitsur

Joseph I Shapiro MD

Background: Obesity, an epidemic among West Virginia children, as well as insulin resistance (IR), is wellestablished contributors to nonalcoholic steatohepatitis (NASH). Progression of NASH can lead to hepatic fibrosis and cirrhosis, making early detection imperative. The standard for diagnosing NASH is histologically via liver biopsy, which is highly invasive and generally contraindicated in children. By studying serum biomarkers associated with NASH, we aim to identify high risk children who can benefit from a less invasive, alternative approach to the early detection of NASH.

Methods: Seventy one children were prospectively recruited and divided into 3 groups: normal weight without IR …

Role Of Serum Biomarkers In Early Detection Of Non-Alcoholic Steatohepatitis And Fibrosis In West Virginian Children, Komal Sodhi, Lucas Bracero, Andrew S. Feyh, Alexandra Nichols, Krithika Srikanthan, Tariq M. Latif, Deborah L. Preston, Joseph I. Shapiro, Yoram Elitsur

Joseph I Shapiro MD

Background: Obesity, an epidemic among West Virginia children, as well as insulin resistance (IR), is wellestablished contributors to nonalcoholic steatohepatitis (NASH). Progression of NASH can lead to hepatic fibrosis and cirrhosis, making early detection imperative. The standard for diagnosing NASH is histologically via liver biopsy, which is highly invasive and generally contraindicated in children. By studying serum biomarkers associated with NASH, we aim to identify high risk children who can benefit from a less invasive, alternative approach to the early detection of NASH.

Methods: Seventy one children were prospectively recruited and divided into 3 groups: normal weight without IR …

Outcomes Of Transcutaneous Aortic Valve Replacement Among High Risk Wv Sample Population., George M. Yousef, Julia Poe, Cameron Killmer, Basel Edris, Jason Mader, Ellen A. Thompson, Daniel Snavely, Silvestre Cansino, Joseph I. Shapiro, Mark A. Studeny

Joseph I Shapiro MD

Introduction:Transcatheter aortic valve replacement (TAVR) is a relatively new strategy for replacing the aortic valve. We elected to review our early experience to see if we could identify clinical characteristics at baseline or immediately following the procedure that would predict death within one year.

Methods:Charts for all patients assigned to receive TAVR procedure at St Mary’s medical center, Huntington, West Virginia between April, 2013 till November, 2016 were identified and reviewed. A total of seventy-two (72) cases were included.

Results: All cause mortality rate at index hospitalization, 30 days, and 12 months was 5.6%(N=4), 6.9%(N=5), 19.4%(N=14) respectively. Stroke …

Role Of Serum Biomarkers In Early Detection Of Diabetic Cardiomyopathy In The West Virginian Population, Adam Shaver, Alexandra Nichols, Ellen A. Thompson, Amrita Mallick, Nandini Manne, Shanmuga Sundaram, Joseph I. Shapiro Md, Komal Sodhi

Joseph I Shapiro MD

Objectives: Diabetic cardiomyopathy (DCM) is an established complication of diabetes mellitus. In West Virginia, the especially high incidence of diabetes and heart failure validate the necessity of developing new strategies for earlier detection of DCM. Since most DCM patients remain asymptomatic until the later stages of the disease when the fibrotic complications become irreversible, we aimed to explore biomarkers that can identify early-stage DCM.

Methods: The patients were grouped into 4 categories based on clinical diabetic and cardiac parameters: Control, Diabetes (DM), Diastolic dysfunction (DD), and Diabetes with diastolic dysfunction (DM+DD), the last group being the preclinical DCM group.

Results: …

Predicting Adverse Outcomes In End Stage Renal Disease: Machine Learning Applied To The United States Renal Data System, Zeid Khitan, Alexis D. Jacob, Courtney Balentine, Adam N. Jacob, Juan R. Sanabria, Joseph I. Shapiro

Joseph I Shapiro MD

We examined machine learning methods to predict death within six months using data derived from the United States Renal Data System (USRDS). We specifically evaluated a generalized linear model, a support vector machine, a decision tree and a random forest evaluated within the context of K-10 fold validation using the CARET package available within the open source architecture R program. We compared these models with the feed forward neural network strategy that we previously reported on with this data set.

Predicting Adverse Outcomes In End Stage Renal Disease: Machine Learning Applied To The United States Renal Data System, Zeid Khitan, Alexis D. Jacob, Courtney Balentine, Adam N. Jacob, Juan R. Sanabria, Joseph I. Shapiro

Joseph I Shapiro MD

We examined machine learning methods to predict death within six months using data derived from the United States Renal Data System (USRDS). We specifically evaluated a generalized linear model, a support vector machine, a decision tree and a random forest evaluated within the context of K-10 fold validation using the CARET package available within the open source architecture R program. We compared these models with the feed forward neural network strategy that we previously reported on with this data set.

Role Of Dietary Components In Modulating Hypertension, Andrew Feyh, Lucas Bracero, Hari Vishal Lakhani, Prasanna Santhanam, Joseph I. Shapiro Md, Zeid Khitan Md, Komal Sodhi

Joseph I Shapiro MD

Hypertension is a major health issue, particularly in medically underserved populations that may suffer from poor health literacy, poverty, and limited access to healthcare resources. Management of the disease reduces the risk of adverse outcomes, such as cardiovascular or cerebrovascular events, vision impairment due to retinal damage, and renal failure. In addition to pharmacological therapy, lifestyle modifications such as diet and exercise are effective in managing hypertension. Current diet guidelines include the DASH diet, a low-fat and low-sodium diet that encourages high consumption of fruits and vegetables. While the diet is effective in controlling hypertension, adherence to the diet is …

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

Joseph I Shapiro MD

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 …

Rapamycin Attenuates Cardiac Fibrosis In Experimental Uremic Cardiomyopathy By Reducing Marinobufagenin Levels And Inhibiting Downstream Pro-Fibrotic Signaling, Steven T. Haller Phd, Yanling Yan Phd, Christopher A. Drummond Phd, Joe Xie Md, Jiang Tian Phd, David J. Kennedy Phd, Victoria Y. Shilova Phd, Zijian Xie Phd, Jiang Liu Phd, Christopher J. Cooper Md, Deepak Malhotra Md, Phd, Joseph I. Shapiro Md, Olga V. Fedorova Phd, Alexei Y. Bagrov Md, Phd

Joseph I Shapiro MD

Background: Experimental uremic cardiomyopathy causes cardiac fibrosis and is causally related to the increased circulating levels of the cardiotonic steroid, marinobufagenin (MBG), which signals through Na/K‐ATPase. Rapamycin is an inhibitor of the serine/threonine kinase mammalian target of rapamycin (mTOR) implicated in the progression of many different forms of renal disease. Given that Na/K‐ATPase signaling is known to stimulate the mTOR system, we speculated that the ameliorative effects of rapamycin might influence this pathway.

Methods and Results: Biosynthesis of MBG by cultured human JEG‐3 cells is initiated by CYP27A1, which is also a target for rapamycin. It was demonstrated that 1 …

Cigarette Smoking And Cardio-Renal Events In Patients With Atherosclerotic Renal Artery Stenosis, Christopher A. Drummond, Pamela S. Brewster, Wencan He, Kaili Ren, Yanmei Xie, Katherine R. Tuttle, Steven T. Haller, Kenneth Jamerson, Lance D. Dworkin, Donald E. Cutlip, Timothy P. Murphy, Ralph B. D'Agostino Sr., William L. Henrich, Jiang Tian, Joseph I. Shapiro Md, Christopher J. Cooper

Joseph I Shapiro MD

Cigarette smoking causes cardiovascular disease and is associated with poor kidney function in individuals with diabetes mellitus and primary kidney diseases. However, the association of smoking on patients with atherosclerotic renal artery stenosis has not been studied. The current study utilized data from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL, NCT00081731) clinical trial to evaluate the effects of smoking on the risk of cardio-renal events and kidney function in this population. Baseline data showed that smokers (n = 277 out of 931) were significantly younger at enrollment than non-smokers (63.3±9.1 years vs 72.4±7.8 years; p<0.001). In addition, patients who smoke were also more likely to have bilateral renal artery stenoses and peripheral vascular disease (PVD). Longitudinal analysis showed that smokers experienced composite endpoint events (defined as first occurrence of: stroke; cardiovascular or renal death; myocardial infarction; hospitalization for congestive heart failure; permanent renal replacement; and progressive renal insufficiency defined as 30% reduction of GFR from baseline sustained for ≥ 60 days) at a substantially younger age compared to non-smokers (67.1±9.0 versus 76.1±7.9, p<0.001). Using linear regression and generalized linear modeling analysis controlled by age, sex, and ethnicity, smokers had significantly higher cystatin C levels (1.3±0.7 vs 1.2±0.9, p<0.01) whereas creatinine and estimated glomerular filtration rate (eGFR) were not different from non-smokers. From these data we conclude that smoking has a significant association with deleterious cardio-renal outcomes in patients with renovascular hypertension.

The Trade-Off Between Dietary Salt And Cardiovascular Disease; A Role For Na/K-Atpase Signaling?, Joe X. Xie, Anna Pearl Shapiro, Joseph I. Shapiro Md

Joseph I Shapiro MD

It has been postulated for some time that endogenous digitalis-like substances, also called cardiotonic steroids (CTS), exist, and that these substances are involved in sodium handling. Within the past 20 years, these substances have been unequivocally identified and measurements of circulating and tissue concentrations have been made. More recently, it has been identified that CTS also mediate signal transduction through the Na/K-ATPase, and consequently been implicated in profibrotic pathways. This review will discuss the mechanism of CTS in renal sodium handling and a potential “trade-off” effect from their role in inducing tissue fibrosis.

Carbonylationmodificationregulatesna/K-Atpasesignalingandsaltsensitivity:Areviewandahypothesis, Preeya Shah Phd, Rebecca Martin, Yanling Yan, Joseph I. Shapiro Md, Jiang Liu

Joseph I Shapiro MD

Na/K-ATPase signaling has been implicated in different physiological and pathophysiological conditions. Accumulating evidence indicates that oxidative stress not only regulates the Na/K-ATPase enzymatic activity, but also regulates its signaling and other functions. While cardiotonic steroids (CTS)-induced increase in reactive oxygen species (ROS) generation is an intermediate step in CTS-mediated Na/K-ATPase signaling, increase in ROS alone also stimulates Na/K-ATPase signaling. Based on literature and our observations, we hypothesize that ROS have biphasic effects on Na/K-ATPase signaling, transcellular sodium transport, and urinary sodium excretion. Oxidative modulation, in particular site specific carbonylation of the Na/K-ATPase α1 subunit, is a critical step in proximal …

Systematic Review Of Metabolic Syndrome Biomarkers: A Panel For Early Detection, Management, And Risk Stratification In The West Virginian Population, Krithika Srikanthan, Andrew Feyh, Haresh Visweshwar, Joseph I. Shapiro Md, Komal Sodhi

Joseph I Shapiro MD

Introduction: Metabolic syndrome represents a cluster of related metabolic abnormalities, including central obesity, hypertension, dyslipidemia, hyperglycemia, and insulin resistance, with central obesity and insulin resistance in particular recognized as causative factors. These metabolic derangements present significant risk factors for cardiovascular disease, which is commonly recognized as the primary clinical outcome, although other outcomes are possible. Metabolic syndrome is a progressive condition that encompasses a wide array of disorders with specific metabolic abnormalities presenting at different times. These abnormalities can be detected and monitored via serum biomarkers. This review will compile a list of promising biomarkers that are associated with metabolic …

Management Of Severe Hyponatremia: Infusion Of Hypertonic Saline And Desmopressin Or Infusion Of Vasopressin Inhibitors?, Antonios H. Tzamaloukas Md, Joseph I. Shapiro Md, Dominic S. Raj Md, Glen H. Murata Md, Deepak Malhotra Md, Phd, Robert H. Glew Phd

Joseph I Shapiro MD

Rapid correction of severe hyponatremia carries the risk of osmotic demyelination. Two recently introduced methods of correction of hyponatremia have diametrically opposite effects on aquaresis. inhibitors of vasopressin V2 receptor (vaptans) lead to the production of dilute urine, whereas infusion of desmopressin causes urinary concentration. Identification of the category of hyponatremia that will benefit from one or the other treatment is critical. In general, vaptans are effective in hyponatremias presenting with concentrated urine and, with the exception of hypovolemic hyponatremia, can be used as their primary treatment. Desmopressin is effective in hyponatremias presenting with dilute urine or developing urinary dilution …

Adiposity Predicts Pulse Pressure In Subjects With Chronic Kidney Disease: Data From The Modification Of Diet In Renal Disease, Preeya T. Shah Phd, Rebecca Martin, Juan R. Sanabria, Zeid Khitan Md, Prasanna Santhanam, Komal Sodhi, Nader G. Abraham, Joseph I. Shapiro Md

Joseph I Shapiro MD

Obesity is a known risk factor for hypertension, but the mechanisms by which this occurs are still unclear. As the body mass index (BMI) is frequently used to define obesity, but the BMI does not distinguish between adipose and other tissues, we sought to develop another index of obesity. We decided to look at the ratio of BMI to urinary creatinine excretion as the latter measurement is believed to be an index of muscle mass. We used data from the modification of diet in renal disease (MDRD) study as urinary creatinine collections and blood pressure measurements were readily available in …

Effect Of Removing Outliers On Statistical Inference: Implications To Interpretation Of Experimental Data In Medical Research, Todd W. Gress, James Denvir, Joseph I. Shapiro

Joseph I Shapiro MD

Background Data editing with elimination of “outliers” is commonly performed in the biomedical sciences. The effects of this type of data editing could influence study results, and with the vast and expanding amount of research in medicine, this effect would be magnified. Methods and Results We first performed an anonymous survey of medical school faculty at institutions across the United States and found that indeed some form of outlier exclusion was performed by a large percentage of the respondents to the survey. We next performed Monte Carlo simulations of excluding high and low values from samplings from the same normal …

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

Joseph I Shapiro MD

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 …

Why Does Obesity Lead To Hypertension? Further Lessons From The Intersalt Study., Preeya T. Shah, Anna P. Shapiro, Zeid Khitan Md, Prasanna Santhanam Md, Joseph I. Shapiro Md

Joseph I Shapiro MD

Objectives To analyze correlations between major determinants of blood pressure (BP), in efforts to generate and compare predictive models that explain for variance in systolic, diastolic, and mean BP amongst participants of the Intersalt study. Methods Data from the Intersalt study, consisting of nearly 10,000 subjects from 32 different countries, were reviewed and analyzed. Published mean values of 24 hour urinary electrolyte excretion (Na+, K+), 24 hour urine creatinine excretion, body mass index (BMI, kg/m^2), and blood pressure data were extracted and imported into Matlab™ for stepwise linear regression analysis. Results As shown earlier, strong correlations between urinary sodium excretion …

Use Of Surface-Enhanced Laser Desorption/Ionization With Time Of Flight (Seldi-Tof) Of The Urine In The Assessment Of Acute Kidney Injury (Aki), David J. Kennedy, Phd, Joseph M. Chan, Dinkar Kaw, Md, Anand M. Ravindaran, Md, Shobha Ratnam, Md, Phd, Deepak Malhotra, Md, Phd, Joseph I. Shapiro Md

Joseph I Shapiro MD

Background: Urinalysis is an important component in the assessment of acute kidney injury (AKI). Proteonomics is a rapidly developing approach in the analysis of physiological states. Several techniques have been developed to screen for protein populations. In this regard SELDI-TOF is a technique based on mass spectroscopy that is being utilized in proteonomics research.

Methods:For this study, clean catch or catheterized urine was collected from normals (n=18) and patients referred to the renal service with AKI. Based upon urine and serum chemistries, clinical parameters, and microscopic urinalysis, the urines were separated into those consistent with prerenal azotemia (n=17) and acute …

Fructose Mediated Non-Alcoholic Fatty Liver Is Attenuated By Ho-1-Sirt1 Module In Murine Hepatocytes And Mice Fed A High Fructose Diet, Komal Sodhi, Nitin Puri, Gaia Favero, Sarah Stevens, Charles Meadows, Nader G. Abraham, Rita Rezzani, Hayden A. Ansinelli, Edward Lebovics, Joseph I. Shapiro

Joseph I Shapiro MD

Background Oxidative stress underlies the etiopathogenesis of nonalcoholic fatty liver disease (NAFLD), obesity and cardiovascular disease (CVD). Heme Oxygenase-1 (HO-1) is a potent endogenous antioxidant gene that plays a key role in decreasing oxidative stress. Sirtuin1 (SIRT1) belongs to the family of NAD-dependent de-acyetylases and is modulated by cellular redox. Hypothesis We hypothesize that fructose-induced obesity creates an inflammatory and oxidative environment conducive to the development of NAFLD and metabolic syndrome. The aim of this study is to determine whether HO-1 acts through SIRT1 to form a functional module within hepatocytes to attenuate steatohepatitis, hepatic fibrosis and cardiovascular dysfunction. Methods …

Use Of Surface-Enhanced Laser Desorption/Ionization With Time Of Flight (Seldi-Tof) Of The Urine In The Assessment Of Acute Kidney Injury (Aki), David Kennedy, Joseph M. Chan, Dinkar Kaw, Anand M. Ravindaran, Deepak Malhotra, Joseph I. Shapiro Md

Joseph I Shapiro MD

Urine SELDI spectra from patients with prerenal azotemia (PRE, lower panels) and acute tubular necrosis (ATN, upper panels) contrasted over ranges between 1.1 and 1.5 KD (left panels) and 2 and 5 KD (right panels).

Predicting Medical Student Success On Licensure Exams, Charles A. Gullo, Michael J. Mccarthy, Joseph I. Shapiro, Bobby L. Miller

Joseph I Shapiro MD

Many schools seek to predict performance on national exams required for medical school graduation using prematriculation and medical school performance data. The need for targeted intervention strategies for at-risk students has led much of this interest. Assumptions that preadmission data and high stakes in-house medical exams correlate strongly with national standardized exam performance needs to be examined. Looking at prematriculation data for predicting USMLE Step 1 performance, we found that MCAT exam totals and math-science GPA had the best prediction from a set of prematriculation values (adjusted R 2 = 11.7 %) for step 1. The addition of scores from …

Uric Acid-Induced Adipocyte Dysfunction Is Attenuated By Ho-1 Upregulation: Potential Role Of Antioxidant Therapy To Target Obesity, Komal Sodhi, Jordan Hilgefort, George Banks, Chelsea Gilliam, Sarah Stevens, Hayden A. Ansinelli, Morghan Getty, Nader G. Abraham, Joseph I. Shapiro, Zeid J. Khitan

Joseph I Shapiro MD

Increased uric acid levels have been implicated in the pathogenesis of metabolic syndrome. To examine the mechanisms by which this occurs, we hypothesized that an increase in heme oxygenase 1, a potent antioxidant gene, will decrease uric acid levels and adipocyte dysfunction via suppression of ROS and xanthine oxidase (XO) levels.We examined the effect of uric acid on adipogenesis in human mesenchymal stem cells (MSCs) in the presence and absence of cobalt protoporphyrin (CoPP), an HO-1 inducer, and tin mesoporphyrin (SnMP), an HO activity inhibitor. Uric acid increased adipogenesis by increasing NADPH oxidase expression and elevation in the adipogenesis markers …

Na/K-Atpase Amplification Of Oxidant Stress; A Universal But Unrecognized Clinical Target?, Zijian Xie, Phd, Joseph I. Shapiro, Md

Joseph I Shapiro MD

The Na/K-ATPase has a signaling function which appears to be separate from its ion pumping function. This signaling function refers to the transduction of conformational changes in the Na/K-ATPase alpha1 subunit into activating Src’s tyrosine kinase activity, triggering a cascade which generates reactive oxygen species (ROS), modulates other signaling pathways, and causes many physiological and pathophysiological effects. We have recently observed that ROS themselves as well as cardiotonic steroids can actually initiate the signal by directly inducing conformational changes in alpha1. It therefore appears that the Na/K-ATPase signal cascade can serve as a feed forward amplification for ROS with circulating …

Peroxisome Proliferator-Activated Receptor Delta Agonist, Hpp593, Prevents Renal Necrosis Under Chronic Ischemia, Larisa V. Fedorova, Komal Sodhi, Cara Gatto-Weis, Nitin Puri, Terry D. Hinds Jr., Joseph I. Shapiro Md, Deepak Malhotra

Joseph I Shapiro MD

The Goldblatt’s 2 kidney 1 clip (2K1C) rat animal model of renovascular hypertension is characterized by ischemic nephropathy of the clipped kidney. 2K1C rats were treated with a specific peroxisome proliferator-activated receptor δ (PPARδ) agonist, HPP593. Clipped kidneys from untreated rats developed tubular and glomerular necrosis and massive interstitial, periglomerular and perivascular fibrosis. HPP593 kidneys did not exhibit any histochemical features of necrosis; fibrotic lesions were present only in perivascular areas. Necrosis in the untreated clipped kidneys was associated with an increased oxidative stress, up regulation and mitochondrial translocation of the pro-death protein BNIP3 specifically in tubules. In the kidneys …

Reactive Oxygen Species Modulation Of Na/K-Atpase Regulates Fibrosis And Renal Proximal Tubular Sodium Handling, Jiang Liu, David J. Kennedy, Yanling Yan, Joseph I. Shapiro Md

Joseph I Shapiro MD

The Na/K-ATPase is the primary force regulating renal sodium handling and plays a key role in both ion homeostasis and blood pressure regulation. Recently, cardiotonic steroids (CTS)-mediated Na/K-ATPase signaling has been shown to regulate fibrosis, renal proximal tubule (RPT) sodium reabsorption, and experimental Dahl salt-sensitive hypertension in response to a high-salt diet. Reactive oxygen species (ROS) are an important modulator of nephron ion transport. As there is limited knowledge regarding the role of ROS-mediated fibrosis and RPT sodium reabsorption through the Na/K-ATPase, the focus of this review is to examine the possible role of ROS in the regulation of Na/K-ATPase …

Management Of Severe Hyponatremia: Infusion Of Hypertonic Saline And Desmopressin Or Infusion Of Vasopressin Inhibitors?, Antonios H. Tzamaloukas Md, Joseph I. Shapiro Md, Dominic S. Raj Md, Glen H. Murata Md, Robert H. Glew Phd, Deepak Malhotra Md, Phd

Joseph I Shapiro MD

Rapid correction of severe hyponatremia carries the risk of osmotic demyelination. Two recently introduced methods of correction of hyponatremia have diametrically opposite effects on aquaresis. Inhibitors of vasopressin V2 receptor (vaptans) lead to the production of dilute urine, whereas infusion of desmopressin causes urinary concentration. Identification of the category of hyponatremia that will benefit from one or the other treatment is critical. In general, vaptans are effective in hyponatremias presenting with concentrated urine and, with the exception of hypovolemic hyponatremia, can be used as their primary treatment. Desmopressin is effective in hyponatremias presenting with dilute urine or developing urinary dilution …

Prieurianin Causes Weight Loss In Diet-Induced Obese Mice And Inhibits Adipogenesis In Cultured Preadipocytes, Ahmed Kablan, Rudel A. Saunders, Maria Szkudlarek-Mikho, Andrew J.B. Chin, Raul M. Bosio, Kazuyuki Fujii, Joseph I. Shapiro M.D., Khew-Voon Chin

Joseph I Shapiro MD

The global increase in the incidence of obesity has emerged as one of the most serious public health risks in recent years. Despite the enormity of the obesity pandemic, there are currently only two FDA-approved therapies for its treatment and these drugs exhibit modest effi cacy and have limiting side effects. Prieurianin is a plant limonoid product that deters feeding in insect larvae. We investigated in this study the effects of prieurianin on weight loss and adipogenesis. Our results showed that prieurianin causes weight loss by reducing energy intake in obese mice on highcalorie diet. We also found that prieurianin …

Down-Regulation Of The Transcription Factor Snail In The Placentas Of Patients With Preeclampsia And In A Rat Model Of Preeclampsia, Larissa Federova, Cara Gatto-Weis, Sleiman Smaili, Nauman Khurshid, Joseph I. Shapiro M.D., Deepak Malhorta, Terrence Horrigan

Joseph I Shapiro MD

Background: Placental malfunction in preeclampsia is believed to be a consequence of aberrant differentiation of trophoblast lineages and changes in utero-placental oxygenation. The transcription factor Snail, a master regulator molecule of epithelial-mesenchymal transition in embryonic development and in cancer, is shown to be involved in trophoblast differentiation as well. Moreover, Snail can be controlled by oxidative stress and hypoxia. Therefore, we examined the expression of Snail and its downstream target, e-cadherin, in human normal term, preterm and preeclamptic placentas, and in pregnant rats that developed preeclampsia-like symptoms in the response to a 20- fold increase in sodium intake. Methods: Western …

Stem Cell Transplantation Increases Antioxidant Effects In Diabetic Mice, Ming Li, Luca Vanella, Yuming Zhang, Ming Shi, Takashi Takaki, Joseph I. Shapiro M.D., Susuma Ikehera

Joseph I Shapiro MD

Intra bone marrow-bone marrow transplantation (IBM- BMT) + thymus transplantation (TT) has been shown to reduce the incidence of graft versus host disease (GVHD) and restore donor-derived T cell function. In addition, an increase in insulin sensitivity occurred in db/db mice after IBM-BMT+TT treatment. Heme oxygenase (HO)-1 is a stress inducible enzyme which exert antioxidant, antiapoptotic, and immune-modulating properties. We examined whether IBM-BMT+TT could modulate the expression of HO-1 in the kidneys of db/db mice. Six-week-old db/db mice with blood glucose levels higher than 250 mg/dl were treated with IBM-BMT+TT. Six weeks later, the db/db mice showed decreased body weight, …