Ramesh Natarajan

Ramesh Natarajan
Virginia Commonwealth University | VCU · Department of Internal Medicine

PhD

About

113
Publications
68,473
Reads
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9,558
Citations
Citations since 2016
32 Research Items
7429 Citations
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201620172018201920202021202202004006008001,0001,2001,400
201620172018201920202021202202004006008001,0001,2001,400
201620172018201920202021202202004006008001,0001,2001,400
Additional affiliations
July 2010 - present
Virginia Commonwealth University
Position
  • Professor (Associate)

Publications

Publications (113)
Article
Full-text available
Vitamin C deficiency disrupts the integrity of connective tissues including bone. For decades this function has been primarily attributed to Vitamin C as a cofactor for collagen maturation. Here, we demonstrate that Vitamin C epigenetically orchestrates osteogenic differentiation and function by modulating chromatin accessibility and priming transc...
Article
Objective: Intraosseous (IO) access is critical in resuscitation, providing rapid access when peripheral vascular attempts fail. Unfortunately, misplacement commonly occurs, leading to possible fluid extravasation and tissue necrosis. Current research exploring the utility of bedside ultrasound in confirming IO line placement is limited by small s...
Article
Background Blood transfusion via single site intraosseous access is a critical modality when caring for a trauma victim that lacks intravascular access. Flow rates and potential clinical compilations when utilizing two sites of intraosseous access are not well known. Materials and Methods Anesthetized adult female Yorkshire swine (Sus scrofa; n =...
Article
Introduction Prolonged field care for junctional wounds is challenging and involves limb movement to facilitate transport. No studies to date have explored the efficacy of gauze products to limit rebleeding in these scenarios. Materials and Methods We randomly assigned 48 swine to QuikClot Combat Gauze, ChitoGauze, NuStat Tactical, or Kerlix treat...
Article
Intravenous (IV) ascorbic acid (AA) improves organ function and reduces inflammation in sepsis, an inflammatory state similar to the post-hematopoietic cell transplant (HCT) milieu. This salutary effect is mediated by antioxidant activity as well transcriptional modulation by AA. HCT recipients are deficient in AA, therefore we evaluated the safety...
Article
Background Vitamin C levels are decreased in arthritis patients and reduced levels following surgery may impair adequate healing. Aim This study measured changes in vitamin C and inflammatory markers in patients undergoing total knee arthroplasty (TKA). Methods Venous blood samples were collected from 10 patients during the preoperative to postop...
Article
Full-text available
Intravenous (IV) ascorbic acid (AA) improves organ function and reduces inflammation in sepsis, an inflammatory state similar to post-hematopoietic cell transplant (HCT) milieu. This salutary effect is mediated by antioxidant activity as well transcriptional modulation by AA. We evaluated the safety and efficacy of IV AA in ameliorating the inflamm...
Article
Introduction Exsanguination remains the leading cause of preventable death in military conflicts, and pediatric casualties are common. Transfusion is crucial to preserve life, but vascular access is challenging in children, so intraosseous (IO) access is often required. However, the optimal transfusion method is unclear. There was therefore the nee...
Article
Background: Current guidelines support intraosseous access for trauma resuscitation when intravenous access is not readily available. However, safety of intraosseous blood transfusions with varying degrees of infusion pressure has not been previously characterized. Materials and methods: Adult female Yorkshire swine (Sus scrofa; n = 36; mean (M)...
Article
Full-text available
The clinical outcome of allogeneic hematopoietic stem cell transplantation (SCT) may be influenced by the metabolic status of the recipient following conditioning, which in turn may enable risk stratification with respect to the development of transplant-associated complications such as graft vs. host disease (GVHD). To better understand the impact...
Article
Background: Fluid resuscitation plays a prominent role in stabilizing trauma patients with hemorrhagic shock yet there remains uncertainty with regard to optimal administration time, volume, and fluid composition (e.g., whole blood, component, colloids) leading to complications such as trauma-induced coagulopathies, acidosis, and poor oxygen trans...
Article
Hematopoietic cell transplantation (HCT) conditioned using myeloablative conditioning (MAC) is complicated by end organ injury due to endothelial dysfunction and graft versus host disease. Mucositis and oxidant injury results in micronutrient deficiency. Ascorbic acid (AA) levels were measured in 15 patients undergoing HCT conditioned with MAC (11...
Article
Background: Military forces render emergency care in marine environments, where care for exsanguination is challenging. However, the effect of saltwater on the functionality of hemostatic agents is unknown. In this study, we used thromboelastography (TEG) to quantify the effect of saltwater on the efficacy of five gauze products. Methods: Blood...
Preprint
Full-text available
Hematopoietic cell transplantation (HCT) conditioned using myeloablative conditioning (MAC) is complicated by end organ injury due to endothelial dysfunction and graft versus host disease. Mucositis and oxidant injury results in micronutrient deficiency. Ascorbic acid (AA) levels were measured in 15 patients undergoing HCT conditioned with MAC (11...
Preprint
Full-text available
The clinical outcome of allogeneic hematopoietic stem cell transplantation (SCT) is strongly influenced from the complications arising during the post-transplant immune restoration and has been well studied and described. However, the metabolic status of the recipient pre-transplant also has the potential to influence this outcome and has never bee...
Article
Poor quality data in preclinical trials can result from inconsistent and unstandardized experimental processes. Unpredictable pre-intervention variability generates unreliable data, biases outcomes and results in needless waste of animals and resources. We applied Define-Measure-Analyse-Improve-Control (DMAIC) quality improvement processes to pilot...
Article
The redox potential of packed red blood cells (RBCs) was measured over a 56-day storage period using a newly developed potentiometric methodology consisting of a nanoporous gold electrode and a silver chloride coated silver reference electrode. Both milliliter- and microliter-sized volumes were separately evaluated. The addition of Vitamin C (VitC)...
Article
Background: Coagulopathy and inflammation induced by hemorrhagic shock and traumatic injury are associated with increased mortality and morbidity. Vitamin C (VitC) is an antioxidant with potential protective effects on the pro-inflammatory and pro-coagulant pathways. We hypothesized that high-dose VitC administered as a supplement to fluid resusci...
Article
Introduction: L-gulonolactone oxidase (Gulo) is the rate limiting enzyme for Vitamin C (VitC) biosynthesis. Humans rely on dietary VitC for collagen synthesis, extracellular matrix formation, and tissue regeneration. VitC deficiency is an unrecognized condition and its role in cardiac homeostasis and post-acute myocardial infarction (AMI) remodelin...
Article
Full-text available
Stored red blood cells (RBCs) undergo oxidative stress that induces deleterious metabolic, structural, biochemical, and molecular changes collectively referred to as "storage lesions". We hypothesized that vitamin C (VitC, reduced or oxidized) would reduce red cell storage lesions, thus prolonging their storage duration. Whole-blood-derived, leuko-...
Article
Full-text available
We report a case of virus-induced acute respiratory distress syndrome (ARDS) treated with parenteral vitamin C in a patient testing positive for enterovirus/rhinovirus on viral screening. This report outlines the first use of high dose intravenous vitamin C as an interventional therapy for ARDS, resulting from enterovirus/rhinovirus respiratory inf...
Article
Full-text available
AIM To examine the effect of high doses of vitamin C (VitC) on ex vivo human platelets (PLTs). METHODS Platelet concentrates collected for therapeutic or prophylactic transfusions were exposed to: (1) normal saline (control); (2) 0.3 mmol/L VitC (Lo VitC); or (3) 3 mmol/L VitC (Hi VitC, final concentrations) and stored appropriately. The VitC addi...
Article
Full-text available
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring au...
Article
Full-text available
This case report summarizes the first use of intravenous vitamin C employed as an adjunctive interventional agent in the therapy of recurrent acute respiratory distress syndrome (ARDS). The two episodes of ARDS occurred in a young female patient with Cronkhite-Canada syndrome, a rare, sporadically occurring, noninherited disorder that is characteri...
Article
Full-text available
Severe systemic inflammatory response to infection results in severe sepsis and septic shock, which are the leading causes of death in critically ill patients. Septic shock is characterised by refractory hypotension and is typically managed by fluid resuscitation and administration of catecholamine vasopressors such as norepinephrine. Vasopressin c...
Article
Vitamin C (VitC) or ascorbic acid (AscA), a cofactor for collagen synthesis and a primary antioxidant, is rapidly consumed post-wounding. Parenteral VitC administration suppresses pro-inflammatory responses while promoting anti-inflammatory and pro-resolution effects in human/murine sepsis. We hypothesised that VitC could promote wound healing by a...
Article
Vitamin C (VitC) or ascorbic acid (AscA), a cofactor for collagen synthesis and a primary antioxidant, is rapidly consumed post-wounding. Parenteral VitC administration suppresses pro-inflammatory responses while promoting anti-inflammatory and pro-resolution effects in human/murine sepsis. We hypothesised that VitC could promote wound healing by a...
Article
Full-text available
Objective: Severe sepsis is a leading cause of mortality and morbidity in the critically ill with no reliably effective treatments. The goal of this study was to determine whether intravenous ascorbic acid impacted novel biomarkers in sepsis. Methods: This is a retrospective study of a phase I, randomized, double-blinded, placebo controlled safety...
Article
Full-text available
Introduction: Macrophage reprogramming is vital for resolution of acute inflammation. Parenteral vitamin C (VitC) attenuates proinflammatory states in murine and human sepsis. However information about the mechanism by which VitC regulates resolution of inflammation is limited. Methods: To examine whether physiological levels of VitC modulate re...
Article
Nuclear factor-κB (NF-κB) and interleukin-6 (IL-6), a NF-κB downstream mediator, play a central role in the inflammatory response of tissues. We aimed to determine the role of the classical NF-κB pathway in severe pulmonary arterial hypertension (PAH) induced by SU5416 and chronic hypoxia (SuHx) in rats. Tissue samples from patients with idiopathic...
Article
Full-text available
Parenterally administered ascorbic acid modulates sepsis-induced inflammation and coagulation in experimental animal models. The objective of this randomized, double-blind, placebo-controlled, phase I trial was to determine the safety of intravenously infused ascorbic acid in patients with severe sepsis. Twenty-four patients with severe sepsis in t...
Article
Full-text available
Background: Multiple organ dysfunction syndrome (MODS) is the principal cause of death in patients with sepsis. Recent work supports the notion that parenteral vitamin C (VitC) is protective in sepsis through pleiotropic mechanisms. Whether suboptimal levels of circulating VitC increase susceptibility to sepsis-induced MODS is unknown. Materials...
Article
Full-text available
Introduction: Neutrophil extracellular trap (NET) formation was recently identified as a novel mechanism to kill pathogens. However, excessive NET formation in sepsis can injure host tissues. We have recently shown that parenteral vitamin C (VitC) is protective in sepsis. Whether VitC alters NETosis is unknown. Methods: We used Gulo-/- mice as t...
Article
Full-text available
Right ventricular failure (RVF) is the most frequent cause of death in patients with pulmonary arterial hypertension (PAH); however, therapies targeted to treat RVF are practically non-existent. Chronic treatment with carvedilol has been shown to reduce established maladaptive right ventricle (RV) hypertrophy and to improve RV function in experimen...
Article
Full-text available
Multiple reports have demonstrated a role for ceramide kinase (CERK) in the production of eicosanoids. To examine the effects of the genetic ablation of CERK on eicosanoid synthesis, primary mouse fibroblasts (MEFs) and macrophages were isolated from CERK-/- and +/+ mice, and the ceramide-1-phosphate (C1P) and eicosanoid profiles were investigated....
Article
Background: Right ventricular (RV) dysfunction (RVD) is the most frequent cause of death in patients with pulmonary arterial hypertension. Although abnormal energy substrate use has been implicated in the development of chronic left heart failure, data describing such metabolic remodeling in RVD remain incomplete. Thus, we sought to characterize m...
Article
Full-text available
Significance: Pathobiological mechanisms that contribute to pulmonary vasoconstriction, lung vascular remodeling, and the development of right heart failure include the generation of reactive oxygen and nitrogen species and the response of lung vascular and cardiac cells to these molecules. We review the information regarding oxidant stress balanc...
Conference Paper
Lung cancer causes more than 1 million deaths worldwide annually [1]. In a recent study by the American Cancer Society in 2011, more than 221,000 new cases of lung cancers were reported [2]. Out of these, the mortality rate was found in roughly 70% of the cases [2]. Lung cancer is divided into two major categories: small cell and non-small cell. In...
Article
Full-text available
Given the relative abundance and toxic potential of acrolein in inhaled cigarette smoke, it is surprising how little is known about the pulmonary and systemic effects of acrolein. Here we test the hypothesis whether systemic administration of acrolein could cause endoplasmic reticulum (ER) stress, and lung cell apoptosis, leading to the enlargement...
Article
Full-text available
Bacterial infections of the lungs and abdomen are among the most common causes of sepsis. Abdominal peritonitis often results in acute lung injury (ALI). Recent reports demonstrate a potential benefit of parenteral vitamin C [ascorbic acid (AscA)] in the pathogenesis of sepsis. Therefore we examined the mechanisms of vitamin C supplementation in th...
Article
Full-text available
Right heart failure is the cause of death of most patients with severe pulmonary arterial hypertensive (PAH) disorders, yet little is known about the cellular and molecular causes of right ventricular failure (RVF). We first showed a differential gene expression pattern between normal rat right and left ventricles, and postulated the existence of a...
Article
Chronic rejection, manifested as small airway fibrosis (obliterative bronchiolitis [OB]), is the main obstacle to long-term survival in lung transplantation. Recent studies demonstrate that the airways involved in a lung transplant are relatively hypoxic at baseline and that OB pathogenesis may be linked to ischemia induced by a transient loss of a...
Article
Full-text available
Diabetes is associated with an increased risk of heart failure, in part explained by endoplasmic reticulum stress and apoptosis. Protein disulfide isomerase (PDI) prevents stressed cardiomyocytes apoptosis. We hypothesized that diabetes impairs PDI function by an alteration in its oxido-reductive state. Myocardial biopsies harvested from the antero...