Prema Gurumurthy

Urinary 8-OHdG: A marker of oxidative stress to DNA and total antioxidant status in essential hypertension with South Indian population.

Establishment of non-invasive urinary biomarker for the early prediction of essential hypertension (EH) is important. We evaluated whether estimation of urinary DNA, serves as a marker to predict the extent of cellular oxidative stress in essential hypertension. A total of 180 South Indian subjects aged 30–65 were recruited for the study. Of these hypertensive subjects investigated, 30 were newly diagnosed and were not on any antihypertensive drugs, but had systolic blood pressure 140–160 mmHg and diastolic blood pressure 95–100 mmHg and 75 hypertensive patients who already on drug therapy for one year and 75 were South Indian normotensive healthy controls with blood pressure ≤ 120/80 mmHg. The 8-OHdG level in urine was significantly increased in hypertensive patients (both newly diagnosed and who already on drug therapy) compared with control group. The significant increase in 8-OHdG was observed in newly diagnosed hypertensive patients compared with hypertensive patients who already on drug therapy. There was a significant decrease in serum TAS value in essential hypertensive group when compared to control group. The urinary 8-OHdG was independently correlated with serum TAS. Decreased TAS levels, which reflect to increased oxidative stress, may be the reason of increased urinary 8-OHdG in South Indian hypertensive patients. Our preliminary data suggest that the competitive ELISA for 8-OHdG appears to be a simple method for quantifying the extent of oxidative stress.

Heart Fatty Acid Binding Protein (H-FABP) as a Diagnostic Biomarker in Patients with Acute Coronary Syndrome

AIMS AND OBJECTIVES Diagnosis of myocardial ischaemia at an early stage in the emergency department is often difficult. A recently proposed biomarker, heart fatty acid binding protein (H-FABP) has been found to appear in the circulation superior to that of cardiac troponins in the early hours of acute coronary syndrome. We proposed to evaluate the levels of H-FABP and ascertain its utility as an early biomarker for acute coronary syndrome (ACS). METHODS AND RESULTS The present study was carried out in 485 subjects, of whom 297 were diagnosed as patients with ACS, 89 were diagnosed as non-cardiac chest pain (NCCP) and 99 people served as healthy controls. H-FABP levels were measured in comparison with standard markers such as troponin I and CK-MB in all subjects enrolled in the study. The levels of H-FABP were significantly raised in patients when compared to controls and NCCP (P<0.001). Receiver Operator Characteristic Curve (ROC) analysis showed H-FABP to be a good discriminator between patients with ischaemic heart disease and patients without ischaemic heart disease. The area under the curve was found to be 0.965 with 95% CI (0.945-0.979). The cut-off value above which H-FABP can be considered positive was found to be 17.7ng/ml. CONCLUSION H-FABP is a promising biomarker for the early detection of patients with acute coronary syndrome.

Pregnancy associated plasma protein-A (PAPP-A) as an early marker for the diagnosis of acute coronary syndrome.

AIMS AND OBJECTIVES Pregnancy associated plasma protein-A (PAPP-A), a metalloproteinase plays a pivotal role in the pathogenesis of atherosclerosis. Recent studies have reported that elevated levels of PAPP-A, signal the onset of acute coronary syndrome (ACS). We, therefore, proposed to study the analytical competence of PAPP-A in patients admitted to the emergency department with chest pain and finally diagnosed as ACS. METHODS AND RESULTS Pregnancy associated plasma protein-A was measured using enzyme-linked immunosorbent assay (ELISA) in 485 patients admitted to emergency care unit, of which 89 patients were diagnosed as Non-cardiac chest pain (NCCP). Elevated levels of PAPP-A were observed in patients diagnosed as ACS on comparison with the controls. Receiver operator characteristic (ROC) curve analysis showed PAPP-A to be a good discriminator between ischaemic and non-ischaemic patients. The area under the curve was found to be 0.904, 95% CI (0.874-0.929) with 90% sensitivity and 85% specificity (P< 0.0001). The cut-off value from the ROC curve was 0.55 μg/mL above which PAPP-A was considered to be positive. CONCLUSION Pregnancy associated plasma protein-A seems to be a promising biomarker for identification and risk stratification for patients with ACS.

Increased serum concentrations of Soluble CD40 Ligand as a prognostic marker in patients with Acute Coronary Syndrome

CD40-CD40L interaction plays a significant role in the pathogenesis of atherosclerosis and coronary artery disease. The clinical predictive value of Soluble CD40 Ligand (sCD40L) was evaluated in patients with Acute Coronary Syndrome (ACS) and Non-Cardiac Chest Pain (NCCP). The levels of serum soluble CD 40 ligand were measured by ELISA in 485 patients admitted to emergency care unit, of which 89 patients were diagnosed as NCCP. The levels of sCD40L were significantly increased in patients with ACS when compared to controls and NCCP. Receiver Operator Characteristic (ROC) Curve analysis showed sCD40L to be a good discriminator between patients with ischemic heart disease and patients without ischemic heart disease. The area under the curve was found to be 0.940 with 95% CI (0.915 to 0.960) (P<0.0001). The cut off value from the ROC curve was 2.99 ng/ml, above which sCD40L was considered to be positive. Combined assessment of sCD40L, Troponin I and CK-MB enhanced the risk prediction and early classification of patients. sCD40L seems to be a promising biomarker for identification and risk stratification for patients with acute coronary syndrome.

Plasma Total Nitric Oxide and Endothelial Constitutive Nitric Oxide Synthase (ecNOS) Gene Polymorphism: A Study in a South Indian Population

In an analysis of the possible association of endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphism and plasma nitric oxide levels in patients with acute coronary syndrome, we investigated 106 patients with the syndrome and 100 healthy controls. Genotype was determined using the polymerase chain reaction; plasma nitric oxide levels were found using ELISA. The genotype frequencies for the a/b polymorphism in the control group were 77% for bb, 19% for ab, and 4% for aa. In the patients, genotype frequencies were 55% bb, 34% ab, and 11% aa. The allele frequencies were 28% a and 72% b among the patients and 13% a and 87% b among control subjects. Our findings showed a significant association of the ecNOS gene polymorphism with acute coronary syndrome in the South Indian population.

Effect of curcumin against oxidation of biomolecules by hydroxyl radicals.

BACKGROUND Among various reactive oxygen species, hydroxyl radicals have the strongest chemical activity, which can damage a wide range of essential biomolecules such as lipids, proteins, and DNA. OBJECTIVE The objective of this study was to investigate the beneficial effects of curcumin on prevention of oxidative damage of biomolecules by hydroxyl radicals generated in in vitro by a Fenton like reaction. MATERIALS AND METHODS We have incubated the serum, plasma and whole blood with H2O2/Cu2+/ Ascorbic acid system for 4 hours at 37 0C and observed the oxidation of biomolecules like albumin, lipids, proteins and DNA. RESULTS Curcumin at the concentrations of 50,100 and 200 μmoles, prevented the formation of ischemia modified albumin, MDA, protein carbonyls, oxidized DNA and increased the total antioxidant levels and GSH significantly. CONCLUSION These observations suggest the hydroxyl radical scavenging potentials of curcumin and protective actions to prevent the oxidation of biomolecules by hydroxyl radicals.

Serum E-selectin levels in Indian children and adolescents: relation to clinical and biochemical parameters.

Background:  An adverse pattern of blood lipids and atherosclerosis begin in childhood. Unfortunately, data for children and adolescents, particularly those in the Indian population, are scarce. The present study aims to evaluate the levels of serum E‐selectin in Indian children and adolescents and its correlation with anthropometric and biochemical parameters.

Serum myeloperoxidase: a novel biomarker for evaluation of patients with acute coronary syndrome

Objectives Myeloperoxidase, an abundant leucocyte enzyme, is elevated in culprit lesions that have ruptured in patients with sudden cardiac injury. Multiple lines of evidence suggest an association between myeloperoxidase and inflammation and acute coronary syndrome. Myeloperoxidase has been proposed as a potent risk marker and diagnostic tool in acute coronary syndrome (ACS). Recent studies have reported the potential use of myeloperoxidase in acute coronary syndrome, but limited reports are available on its utility in different groups of ACS in the emergency department. Therefore the circulating levels of serum myeloperoxidase in patients with acute coronary syndrome and control subjects were studied. Design and setting The levels of serum myeloperoxidase were measured by ELISA in 485 patients admitted to emergency care unit, of which 89 patients were diagnosed as non-cardiac chest pain (NCCP). The levels of myeloperoxidase were significantly increased in patients with ACS when compared with controls and NCCP. From the receiver operator characteristic (ROC) curve analysis, the optimum value above which myeloperoxidase can be considered positive was found to be 48.02 U/ml. The area under the curve was found to be 0.956 with 95% CI (0.934 to 0.973) (p<0.0001). A combination analysis of ROC curves of troponin, creatine kinase MB (CK-MB) and myeloperoxidase showed myeloperoxidase to be highly significant. Multivariate analysis revealed myeloperoxidase to be an independent diagnostic marker for early diagnosis of ACS. Conclusion Myeloperoxidase, in contrast to troponin and CK-MB, identified patients at risk of ischaemic events, even in the absence of myocardial necrosis, thus highlighting its potent usefulness for risk stratification among patients presenting with chest pain.

Identification of Predictable Biomarkers in Conjunction to Framingham Risk Score to Predict the Risk for Cardiovascular disease (CVD) in Non Cardiac Subjects

INTRODUCTION Although the cardiovascular disease (CVD) burden is rising in different countries, the morbidity and mortality rate is not reduced to much extent because of lack of application of the biomarkers for diagnosing CVD. Hence, we aimed to establish the predictable biomarkers in conjunction to framingham risk score in order to predict the risk for CVD in non cardiac patients. MATERIALS AND METHODS Three hundred subjects were screened for the study who came for the master health checkup. Out of them 50 patients were excluded as they were under medication. 23 patients were excluded due to various systemic diseases like fever and infection etc. The remaining of 227 patients with age range of 30-80 y was randomly selected for investigation. These subjects were divided into four different groups: Group I - controls with age range: 30-60 y (n=50) these subjects were free from all the systemic ailments and risk factors. Study groups comprised of Group II - (n=44) with age range: 30-40 y, Group III - (n=50) with age range: 41-50 y and Group IV - (n=83) with age range: 51-80 y. Patients with different risk factors without medication participated as study groups. Routine biochemical parameters were analysed using fully automated analyser and atherosclerotic biomarkers was analysed using ELISA kit. In addition to this, framingham risk scores was calculated in all the groups, for 30 y risk prognosis for CVD. RESULTS The atherosclerotic biomarkers such as E-selectin, Leptin, osteoprotegerin (OPG) and Ox-LDL were elevated among the study groups as compared to control group. Pearson correlation showed a significant association between the individual risk score (30 y framingham risk for CVD) of individuals, and the above biomarkers. The Receiver operating curve (ROC) analysis also showed a greater area under curve with higher sensitivity and specificity. CONCLUSION We conclude the application E-Selectin, leptin, OPG and Ox-LDL as biomarkers along with the framingham risk scores in prediction risk for CVD in the individuals with subclinical atherosclerosis. It is more reliable and predictable as compared to the individual biomarkers alone.

Lipid Profile and Non-enzymic Antioxidant Status in Patients with Acute Coronary Syndrome in South India

AIMS AND OBJECTIVES Elevated lipid profile and reduced antioxidants accelerate the formation of atherosclerosis. Multiple lines of evidences have suggested that increased lipids and low antioxidants are the major risk factors for the incidence of acute coronary syndrome. Oxidative stress evaluation is now considered as an index for the assessment of development of coronary artery disease. Therefore, we studied association of the levels of non-enzymic antioxidants and lipid profile in controls and patients with acute coronary syndrome (ACS). METHODS AND RESULTS The present study was carried out on 485 patients admitted to the emergency care unit, of whom 89 patients were diagnosed as non-cardiac chest pain (NCCP). Total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were analysed along with non-enzymic antioxidants such as vitamin C, vitamin E, reduced glutathione, MDA and protein thiol in controls and patients with ACS. The levels of total cholesterol and LDL-cholesterol were significantly raised in patients when compared to controls in contrast to lowering of HDL-cholesterol levels in patients than controls. Vitamin C, vitamin E, reduced glutathione, MDA and protein thiol levels were significantly lowered in patients than controls (p<0.05). CONCLUSION Oxidative stress and lipid profile should be included as important markers in the early detection of acute coronary syndrome.