71 results on '"Sridhar MG"'
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2. Insulin Plant (Costus pictus) extract restores thyroid hormone levels in experimental hypothyroidism
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Bobby, Zachariah, primary, Ashwini, S, additional, Sridhar, MG, additional, and Cleetus, CC, additional
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- 2017
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3. Association of sympathovagal imbalance with arterial stiffness indices in women with risk factors for pregnancy-induced hypertension in first and third trimesters of gestation
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Pal, Pravati, primary, Pal, GopalKrushna, additional, Sridhar, MG, additional, Subha, Manivannan, additional, Syed, Habeebullah, additional, and Adithan, Chandrasekaran, additional
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- 2014
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4. Bitter gourd (Momordica charantia) improves insulin sensitivity by increasing skeletal muscle insulin-stimulated IRS-1 tyrosine phosphorylation in high-fat-fed rats.
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Sridhar MG, Vinayagamoorthi R, Arul Suyambunathan V, Bobby Z, and Selvaraj N
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- 2008
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5. Exploring faculty perspectives on competency-based medical education: A report from India.
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Ramanathan R, Shanmugam J, Sridhar MG, Palanisamy K, and Narayanan S
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Introduction: Medical education in India is experiencing a paradigm shift from traditional curriculum to competency-based medical education (CBME). It de-emphasizes time-based training and promises greater accountability, flexibility, and learner centeredness. Faculty development is integral in the context of CBME. Considering faculty perceptions toward the new CBME and addressing the difficulties will play a vital role in successful implementation., Materials and Methods: A cross-sectional study was carried out among 297 teaching faculty in 91 medical colleges across 20 states all over India between February and July 2020. A structured validated questionnaire on CBME was used to collect the responses through Google forms and was exported and analyzed in Microsoft Excel., Results: More than 80% opined that Faculty members in departments are not adequate for successful CBME implementation. Reflective learning, early clinical exposure, and elective posting were accepted by 60.2%, 70.4%, and 45.5% of the faculty, respectively. Around 81.8% welcomed horizontal integration, whereas only 54.2% favored vertical integration during the Phase I MBBS., Conclusion: Few reforms such as curtailing the duration of foundation course, sensitization of all medical teachers through faculty development programs, better synchronized vertical integration, increasing the strength of faculty in each department, and adequate infrastructure for skills laboratory can be undertaken as per faculty suggestions., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Education and Health Promotion.)
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- 2021
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6. Role of Zinc in Neonatal Sepsis.
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Banupriya N, Bhat BV, and Sridhar MG
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- Dietary Supplements, Humans, Infant, Infant, Newborn, Zinc therapeutic use, Neonatal Sepsis drug therapy, Sepsis drug therapy, Trace Elements therapeutic use
- Abstract
Sepsis emerges as a complex clinical syndrome with activation of an innate host response to infections. Despite advancement in therapeutic approaches, infants with sepsis remain hospitalized for longer durations and it remains to be a major health problem in today's world. Zinc as a trace element, has the potential to improve the host's defence mechanism against various pathogenic diseases. During sepsis, a redistribution of zinc from serum into the liver has been observed and earlier studies imply a correlation between serum zinc levels and the outcome of sepsis. Zinc also appears to have a potential to be used as a biomarker of sepsis outcome. There are only few reports available to show the efficacy of zinc supplements in the management of neonatal sepsis.
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- 2021
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7. Effect of zinc supplementation on relative expression of immune response genes in neonates with sepsis: A preliminary study.
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Banupriya N, Bhat BV, Vickneshwaran V, and Sridhar MG
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- Dietary Supplements, Humans, Immunity genetics, Infant, Newborn, Tumor Necrosis Factor-alpha genetics, Zinc, Neonatal Sepsis drug therapy, Neonatal Sepsis genetics, Sepsis drug therapy, Sepsis genetics
- Abstract
Background & Objectives: Zinc alters gene expression mainly by binding to a site on the transcription factor. Genome-wide expression studies have shown early repression of genes related to zinc and immunity in adult patients with sepsis. The present study was conducted to evaluate the role of zinc supplementation on relative expression of immune response genes in neonatal sepsis., Methods: In the present study, a sample of convenience of 22 neonates each was selected from the zinc supplemented and control groups using random numbers for expression of immune-related genes by zinc supplementation. These neonates with sepsis were earlier randomized into two groups: with and without zinc supplementation in addition to standard antibiotics and supportive care. Relative expression of immune response genes were analyzed for 22 neonates in each group using quantitative real-time PCR for calprotectin (S100A8/A9), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), toll-like receptor-4 (TLR-4), cluster of differentiation 14 (CD14) and lipopolysaccharide-binding protein (LBP) genes., Results: An increase in serum zinc levels was observed in zinc-supplemented group compared to controls. S100A8 gene showed downregulation by three-fold (P <0.001) and S100A9 gene showed upregulation by two-fold (P <0.05) in zinc group compared to controls. CD14 gene showed upregulation by one-fold in zinc-supplemented group compared to controls (P <0.05). No significant fold changes were observed with respect to TNF-α, IL-6, LBP and TLR-4 genes between the two groups., Interpretation & Conclusions: The results of our preliminary study showed that the zinc supplementation might modulates the relative expression of immune-related genes involved in sepsis pathway among neonates. However, studies with larger sample size are needed to be done to provide a better picture on the outcome by gene expression in neonatal sepsis by zinc supplementation., Competing Interests: None
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- 2020
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8. Evaluation of Serum Vitamin D Levels in Diabetic Foot Infections: A Cross-Sectional Study in a Tertiary Care Center in South India.
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Danny Darlington CJ, Suresh Kumar S, Jagdish S, and Sridhar MG
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Background: The impact of diabetic foot infections is enormous in India. Studies on vitamin D levels in diabetes mellitus foot infections are scarce. The primary objective of the present study was to compare the serum vitamin D level between diabetics with foot infections and those without foot infections and the secondary objective was to assess the association between the vitamin D level and the severity of foot infections and outcomes., Methods: The study included 176 type 2 diabetics who attended Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India, between September 2012 and June 2014. The serum vitamin D level was measured for 88 diabetics with foot infections (Group 1) and 88 without foot infections (Group 2) using the ELISA 25OH vitamin D DIAsource kit (DIAsource ImmunoAssays S.A., Belgium) and compared. Both groups were followed up for 6 months for outcomes. The qualitative variables were analyzed using the χ2 test and the quantitative variables using the Student t test. The statistical analyses were performed using SPSS, version 17.0. A P value of less than 0.05 was considered significant., Results: The mean serum vitamin D level was not significantly different between the two groups (P=0.306). Among the patients in Group 1 who either required amputations or died, 97.44% had subnormal vitamin D levels in contrast to 59.18% in those who were grafted or achieved wound healing (P=0.001). Among those who achieved wound healing within 6 months, 78.9% had normal vitamin D levels (P=0.0006)., Conclusion: The study found no significant difference in the serum level of vitamin D between diabetics with and without foot infections. However, vitamin D deficiency was associated with a poor outcome in diabetics with foot infections., Competing Interests: Conflict of Interest: None declared., (Copyright: © Shiraz University of Medical Sciences.)
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- 2019
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9. Irisin and Visfatin Predicts Severity of Diabetic Nephropathy.
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Mageswari R, Sridhar MG, Nandeesha H, Parameshwaran S, and Vinod KV
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Although the roles of irisin and visfatin have been well established in diabetes mellitus, there are limited studies about their association in diabetic nephropathy. The present study was designed to assess the levels of irisin and visfatin and their association with the severity of diabetic nephropathy. 43 diabetic nephropathy cases and 43 diabetic subjects without nephropathy were enrolled in the study. Serum levels of irisin and visfatin were compared in both the groups. Irisin and visfatin were significantly increased in diabetic nephropathy cases when compared with diabetes subjects without nephropathy. eGFR was negatively correlated with visfatin (r = -0.323, p = 0.034), irisin (r = -0.324, p = 0.034), urine albumin (r = -0.443, p = 0.003) and albumin creatinine ratio (r = -0.419, p = 0.005) in patients with diabetic nephropathy. Visfatin was significantly elevated in stage IV nephropathy compared with stage III nephropathy. We conclude that irisin and visfatin are elevated in diabetic nephropathy and can be an index of its severity., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest.
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- 2019
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10. WITHDRAWN: Soy isoflavones (from Glycine max) preserves hepatocellular free radical defense system potential and ameliorates inflammatory response in high fat fed ovariectomised Wistar rats: The molecular mechanisms.
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Panneerselvam S, Packirisamy RM, Bobby Z, and Sridhar MG
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This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)
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- 2019
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11. CA 125 is a better marker to differentiate endometrial cancer and abnormal uterine bleeding.
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Nithin KU, Sridhar MG, Srilatha K, and Habebullah S
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- Adult, Age Factors, Biomarkers, Tumor, Body Mass Index, Carcinoembryonic Antigen blood, Diagnosis, Differential, Female, Humans, India, Menopause metabolism, Middle Aged, Mucin-1 blood, Prolactin blood, Sensitivity and Specificity, CA-125 Antigen blood, Endometrial Neoplasms blood, Endometrial Neoplasms diagnosis, Uterine Hemorrhage blood, Uterine Hemorrhage diagnosis
- Abstract
Background: Incidence of endometrial cancer in India is increasing due to lifestyle changes and obesity. As 5 year survival rate of cancer confined to uterus is good, there is need for serum tumor marker for early diagnosis. This study was designed to identify a tumor marker which differentiate endometrial carcinoma and abnormal uterine bleeding (AUB) because common presentation of endometrial carcinoma is AUB., Objectives: To estimate and compare serum prolactin, Cancer Antigen 125 (CA-125), Cancer Antigen 15-3 (CA15-3), and Carcino embryonic antigen (CEA) levels in patients with endometrial cancer and abnormal uterine bleeding; To evaluate the role of these markers in diagnosing endometrial cancer., Methodology: Thirty eight patients with endometrial cancer and 40 patients with AUB were recruited in this study. Serum prolactin, CA 125, CEA, and CA 15-3 levels were estimated in both groups., Results: The levels of CA 15-3, CA 125, CEA, and prolactin were increased in endometrial carcinoma patients, on comparison with AUB patients. CA 125 alone was found to be a better marker to detect endometrial cancer with 52.63% sensitivity, 80.00% specificity., Conclusion: As individual tumor marker, serum CA 125 has the ability to detect endometrial cancer in patients with abnormal uterine bleeding.
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- 2018
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12. Exploring circulatory shock and mortality in viper envenomation: a prospective observational study from India.
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Gopalakrishnan M, Vinod KV, Dutta TK, Shaha KK, Sridhar MG, and Saurabh S
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- Adult, Animals, Antivenins administration & dosage, Capillary Leak Syndrome etiology, Disseminated Intravascular Coagulation etiology, Female, Hemorrhage etiology, Humans, India epidemiology, Logistic Models, Male, Multivariate Analysis, Pituitary-Adrenal System blood supply, Prognosis, Prospective Studies, Risk Factors, Shock etiology, Snake Bites drug therapy, Viper Venoms toxicity, Hemorrhage epidemiology, Hospital Mortality, Shock epidemiology, Snake Bites complications, Snake Bites mortality
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Background: Viper envenomation contributes to nearly 50% of snake-bite deaths in India, chiefly due to circulatory shock. The mechanisms leading to circulatory shock include bleeding, capillary leak syndrome (CLS) and myocardial depression. Pituitary-adrenal axis involvement in circulatory shock, though described, has not been fully elucidated., Aim: To identify predictors of circulatory shock and mortality in viper envenomation and explore the role of pituitary-adrenal axis in circulatory shock., Design: Prospective hospital-based observational study., Methods: Once a syndromic diagnosis of viper envenomation was made, relevant clinical and laboratory data were collected. Serum cortisol was estimated in those with circulatory shock. Post-mortem examination of pituitary, kidneys and adrenals was performed. Adjusted odds-ratios were calculated for respective risk-factors for shock and mortality using multivariable logistic regression with backward elimination strategy., Results: Of 248 patients of viper envenomation treated at our hospital, circulatory shock was present in 19% and in-hospital mortality was 23%. CLS, circulatory shock, bleeding and requirement of > 20 vials of antivenom predicted mortality. Ischaemic and haemorrhagic necrosis of pituitary or adrenals was present in 51% of post-mortem specimens. Disseminated intravascular coagulation (DIC) and CLS were strong predictors of pituitary haemorrhage., Conclusion: Predictors of mortality - bleeding, CLS and requirement of high antivenom doses are warning signs which can alert clinicians to patients who may have poor outcomes. Our study points to a definite role of pituitary-adrenal axis in circulatory shock supports the hypothesis that pituitary involvement in viper envenomation closely resembles Sheehan syndrome. The mechanism of pituitary involvement appears to be a result of increased susceptibility of the swollen gland secondary to CLS and micro thrombi deposition in DIC.
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- 2018
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13. Clomiphene citrate increases nitric oxide, interleukin-10 and reduces matrix metalloproteinase-9 in women with polycystic ovary syndrome.
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Sylus AM, Nandeesha H, Sridhar MG, Chitra T, and Sreenivasulu K
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- Adult, Clomiphene pharmacology, Female, Fertility Agents, Female pharmacology, Follow-Up Studies, Humans, Ovulation drug effects, Polycystic Ovary Syndrome blood, Pregnancy, Pregnancy Rate, Young Adult, Clomiphene therapeutic use, Fertility Agents, Female therapeutic use, Interleukin-10 blood, Matrix Metalloproteinase 9 blood, Nitric Oxide blood, Polycystic Ovary Syndrome drug therapy
- Abstract
Objectives: Matrix metalloproteinase-9, Nitric oxide and inflammation plays a role in the pathogenesis of poly cystic ovary syndrome (PCOS). Even though these parameters are altered in PCOS, the effect of clomiphene citrate on them has not been studied till date. The present study was done to assess the effect of clomiphene citrate on matrix metalloproteinase-9, nitric oxide and interleukin-10 levels in women with PCOS., Study Design: 72 women diagnosed with PCOS were enrolled in the study. Matrix metalloproteinase-9, nitric oxide and interleukin-10 levels were compared at baseline and after three weeks following Clomiphene citrate treatment., Results: Clomiphene citrate increases both nitric oxide (p = 0.03) and interleukin-10 (p < 0.001) levels and reduces matrix metalloproteinase-9 levels (p < 0.001) in women with PCOS. It also improves the ovulation rate (52.8%) and clinical pregnancy rate (19.4%) in PCOS. Also there was a significant reduction in matrix metalloproteinase-9 levels in both the ovulatory (p < 0.001) and conceived groups (p = 0.024) compared to non ovulatory and non conceived group. There was no difference in nitric oxide and interleukin-10 levels in ovulatory and conceived groups compared to non ovulatory and non conceived group., Conclusion: We conclude that clomiphene citrate increases the levels of nitric oxide and interleukin-10 and decreases the matrix metalloproteinase - 9 levels and improves the ovulation rate and clinical pregnancy rate in PCOS., (Copyright © 2018 Elsevier B.V. All rights reserved.)
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- 2018
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14. Short Term Oral Zinc Supplementation among Babies with Neonatal Sepsis for Reducing Mortality and Improving Outcome - A Double-Blind Randomized Controlled Trial.
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Banupriya N, Bhat BV, Benet BD, Catherine C, Sridhar MG, and Parija SC
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- Administration, Oral, Double-Blind Method, Female, Humans, Infant, Newborn, Male, Neonatal Sepsis mortality, Treatment Outcome, Zinc Sulfate administration & dosage, Zinc Sulfate blood, Neonatal Sepsis drug therapy, Zinc Sulfate therapeutic use
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Objective: To evaluate the efficacy of short term zinc supplementation on the mortality rate and neurodevelopment outcome in neonates with sepsis at 12 mo corrected age., Methods: The clinical trial was undertaken in the neonatal intensive care unit of JIPMER during the time period from September 2013 through December 2016. Neonates with clinical manifestations of sepsis who exhibited two positive screening tests (microESR, C- reactive protein, band cell count) were included and randomized into no zinc and zinc group. The intervention was zinc sulfate monohydrate given at a dose of 3 mg/kg twice a day orally for 10 d along with standard antibiotics. The no zinc group was on antibiotic treatment. Blood samples from both groups were collected at baseline and after day 10. Babies were carefully discharged from the hospital. The babies were followed up till 12 mo corrected age using DASII (Development Assessment Scale for Indian Infants)., Results: At the time of enrolment, patient characteristics were similar in both the groups. The mortality rate was significantly higher in no zinc compared to zinc group (5 vs. 13; P = 0.04). Although motor development quotient was similar, mental development quotient was significantly better among babies who received zinc supplementation., Conclusions: Short term zinc supplementation of newborns with sepsis reduces mortality and improves mental development quotient at 12 mo of age.
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- 2018
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15. Effect of 12 Weeks of Yoga Therapy on Quality of Life and Indian Diabetes Risk Score in Normotensive Indian Young Adult Prediabetics and Diabetics: Randomized Control Trial.
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Keerthi GS, Pal P, Pal GK, Sahoo JP, Sridhar MG, and Balachander J
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Introduction: India has become the epicentre for diabetes, a stress-related disorder affecting the working skills and day-to-day lifestyle management of younger population. Most of the studies have reported the effect of yoga on improving Quality of Life (QoL) in diabetic patients with other comorbidities. Till date, no randomized control trial reports are available to show the effect of yoga therapy on QoL and Indian Diabetes Risk Score (IDRS) in normotensive prediabetic and diabetic young individuals., Aim: To determine the effect of 12 weeks of yoga therapy on QoL and IDRS among normotensive prediabetic and diabetic young Indian adults., Materials and Methods: A randomized control trial was conducted in Endocrinology Outpatient Department (OPD). Normotensive participants (n=310) aged 18-45 years were divided into healthy controls (n=62), prediabetics (n=124) and diabetics (n=124). Study group subjects were randomly assigned to Group II (n=62, prediabetes-standard treatment), Group III (n=62, prediabetes-standard treatment + yoga therapy), Group IV (n=62, diabetes-standard treatment) and Group V (n=62, diabetes-standard treatment + yoga therapy). Flanagan QoL scale, IDRS questionnaire, Fasting Plasma Glucose (FPG) and insulin were assessed pre and post 12 weeks of intervention. Statistical analysis was done using Student's paired t-test and one-way ANOVA., Results: Pre-post intervention analysis showed significant improvement in QoL scale with p<0.01 in Group II and Group IV; p<0.001 in Group III and Group V respectively. There was significant reduction in IDRS in Group II (p<0.05); p<0.001 in Group III, Group IV and Group V respectively. Significant difference (p<0.001) in QoL scale and IDRS were found when study groups with standard treatment along with yoga therapy were compared to standard treatment alone., Conclusion: Yoga therapy along with standard treatment for 12 weeks improved QoL and attenuated the diabetes risk among Indian prediabetics and diabetics compared to standard treatment alone.
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- 2017
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16. Efficacy of zinc supplementation on serum calprotectin, inflammatory cytokines and outcome in neonatal sepsis - a randomized controlled trial.
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Banupriya N, Vishnu Bhat B, Benet BD, Sridhar MG, and Parija SC
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- Administration, Oral, Anti-Bacterial Agents, Biomarkers blood, Case-Control Studies, Drug Administration Schedule, Female, Humans, Infant, Newborn, Infant, Premature, Interleukin-6, Kaplan-Meier Estimate, Male, Neonatal Sepsis blood, Neonatal Sepsis mortality, Zinc blood, Leukocyte L1 Antigen Complex blood, Neonatal Sepsis drug therapy, Tumor Necrosis Factor-alpha blood, Zinc Sulfate administration & dosage
- Abstract
Objective: To find out the efficacy of zinc supplementation in decreasing the levels of serum calprotectin and inflammatory cytokines with improvement in outcome in neonatal sepsis., Methods: Neonates with clinical signs suggestive of sepsis and at least two screening tests positive were randomized into two groups - zinc group and control group. The zinc group received 3 mg/kg of zinc sulfate monohydrate twice a day orally for 10 days along with antibiotics. The control group received antibiotics and supportive care. Serum zinc, calprotectin, TNF-α and IL-6 were estimated in serum at recruitment and 10 days later after completion of antibiotics. The babies were monitored daily till discharge and mortality rate was compared between the groups., Results: Baseline characteristics were similar between the groups. Serum zinc levels were considerably increased in the zinc group after supplementation. There was significant decline in concentrations of serum calprotectin, TNF-α and IL-6 (p < 0.05) in the zinc group. In the control group also, serum calprotectin and IL-6 levels were found to be decreased significantly after antibiotic treatment (p < 0.05), while TNF-α showed insignificant reduction. Kaplan-Meier analysis was performed to assess the survival time between the groups. The mortality was lower in the zinc group compared to the control group 5 versus 11, p= 0.12., Conclusion: Neonates with sepsis who received zinc in addition to antibiotics showed significant reduction in serum calprotectin and inflammatory cytokines. Although mortality was lower in zinc group, it was not statistically significant.
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- 2017
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17. An exploratory study of immune markers in acute and transient psychosis.
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Mahadevan J, Sundaresh A, Rajkumar RP, Muthuramalingam A, Menon V, Negi VS, and Sridhar MG
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- Acute Disease, Adolescent, Adult, Female, Follow-Up Studies, Humans, Inpatients, Male, Middle Aged, Pilot Projects, Young Adult, Hydrocortisone blood, Interleukin-6 blood, Psychotic Disorders blood, Psychotic Disorders physiopathology, Transforming Growth Factor beta blood, Tumor Necrosis Factor-alpha blood
- Abstract
The aim of this study was to look into the balance of pro-inflammatory (TNF-α, IL-6) and anti-inflammatory (TGF-β) cytokines and their association with stress, alterations in HPA axis activity and the disease severity in acute psychosis. Socio-demographic and clinical details were collected from 41 in-patients with a diagnosis of Acute and Transient Psychotic Disorder. Holmes and Rahe Stress Scale for stress in the preceding year, and Brief Psychiatric Rating Scale at baseline and follow up (4-12 weeks) for psychopathology were applied. IL-6, TNF-α (pro-inflammatory), TGF-β (anti-inflammatory) and Cortisol (morning and afternoon values) were measured at baseline and follow up. A total of 30 out of 41 cases recruited had follow up data available. The levels of IL-6 (p<0.001), TNF-α (p<0.001) and TGF-β (p<0.001) at baseline were all found to be significantly elevated compared to 42 age and gender matched healthy controls. There was a significant increase in the levels of TNF-α (p=0.020) and morning levels of cortisol (p=0.009) and a significant decrease in the levels of TGF-β (p=0.004) and afternoon levels of cortisol (p=0.043) from baseline to follow up. This study showed that there was an increased level of both pro and anti-inflammatory cytokines at baseline and a prolonged pro - inflammatory compared to anti - inflammatory response which warrants larger prospective studies and comparative studies to patients with schizophrenia and bipolar disorders., (Copyright © 2016 Elsevier B.V. All rights reserved.)
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- 2017
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18. Insulin Plant ( Costus pictus ) Extract Restores Thyroid Hormone Levels in Experimental Hypothyroidism.
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Ashwini S, Bobby Z, Sridhar MG, and Cleetus CC
- Abstract
Background: The aim of the present study was to investigate the preventive effect of Costus pictus leaf extract in experimental hypothyroidism., Materials and Methods: Forty male Wistar rats were randomly divided into four groups with ten rats in each group: Control (C), hypothyroid (H), control+extract (C+E), and hypothyroid+extract (H+E). Rats in C group did not receive any intervention throughout the experimental period. The rats in the C+E and H+E groups received pretreatment with C. pictus leaf extract for 4 weeks. Subsequently, for the next 6 weeks, rats in the H group received 0.05% propylthiouracil in drinking water while C+E group received C. pictus leaf extract and H+E group received propyl thiouracil and C. pictus leaf extract., Results: Hypothyroid group rats exhibited dramatic increase in thyroid-stimulating hormone (TSH) levels with concomitant depletion in the levels of thyroid hormones. Treatment with the extract resulted in remarkable improvement in thyroid profile. Extract produced 10.59-fold increase in plasma free T3, 8.65-fold increase in free T4, and 3.59-fold decrease in TSH levels in H+E group in comparison with H group. Treatment with the extract ameliorated hypercholesterolemia, decreased levels of plasma C-reactive protein and tumor necrosis factor alpha, suppressed tissue oxidative stress and prevented hepatic and renal damage caused due to thyroid hormone depletion in the H+E group. Pentacyclic triterpenes alpha and beta amyrins were identified and quantified in the extract., Conclusions: This is the first study to reveal that C. pictus extract has therapeutic potential to restore thyroid hormone levels and prevent the biochemical complications due to thyroid hormone insufficiency in the animal model of experimental hypothyroidism., Summary: The preventive effect of Costus pictus leaf extract in experimental hypothyroidism was evaluated in the present study.Hypothyroidism was induced in the experimental animals by giving 0.05% propylthiouracil in drinking water.Hypothyroid rats exhibited dramatic increase in thyroid-stimulating hormone (TSH) levels with concomitant depletion in the levels of thyroid hormones.Treatment with Costus pictus leaf extract in hypothyroid rats significantly improved the thyroid profile. It also ameliorated hypercholesterolemia, decreased the levels of plasma inflammatory markers, suppressed tissue oxidative stress and prevented hepatic and renal damage caused due to thyroid hormone depletion.The possible active principles alpha and beta amyrins were identified and quantified in the extract through LC-MS. Abbreviations Used: APCI: Atmospheric pressure chemical ionization; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; C group: Control group; C+E group: Control+extract group; C. pictus : Costus pictus ; CRP: C-reactive protein; DPPH: 2,2-diphenyl-1-picrylhydrazyl; FRAP: Ferric reducing antioxidant power; HDL: High-density lipoprotein; H group: Hypothyroid group; H+E group: Hypothyroid+extract group; LDL: Low-density lipoprotein; LC-MS: Liquid chromatography-mass spectrometry; MDA: Malondialdehyde; PTU: 6-Propyl-2-thiouracil; SRM: Single reaction monitoring; TSH: Thyroid-stimulating hormone; TPTZ: 2,4,6-tri-(2-pyridyl)-5-triazine; TBA: 2-Thiobarbituric acid; TG: Triglyceride; TNFα: Tumor necrosis factor alpha; TAS: Total antioxidant status., Competing Interests: There are no conflicts of interest.
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- 2017
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19. Soy isoflavones (Glycine max) ameliorate hypertriglyceridemia and hepatic steatosis in high fat-fed ovariectomized Wistar rats (an experimental model of postmenopausal obesity).
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Panneerselvam S, Packirisamy RM, Bobby Z, Elizabeth Jacob S, and Sridhar MG
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- Animals, Biomarkers blood, Biomarkers metabolism, Diet, High-Fat, Dyslipidemias complications, Dyslipidemias metabolism, Dyslipidemias pathology, Dyslipidemias prevention & control, Female, Humans, Hypertriglyceridemia complications, Hypertriglyceridemia metabolism, Hypertriglyceridemia pathology, Lipid Metabolism, Liver metabolism, Liver pathology, Metabolic Syndrome complications, Metabolic Syndrome metabolism, Metabolic Syndrome pathology, Metabolic Syndrome prevention & control, Non-alcoholic Fatty Liver Disease complications, Non-alcoholic Fatty Liver Disease metabolism, Non-alcoholic Fatty Liver Disease pathology, Obesity complications, Organ Size, Osteoporosis, Postmenopausal complications, Ovariectomy, Random Allocation, Rats, Wistar, Dietary Supplements, Disease Models, Animal, Hypertriglyceridemia prevention & control, Isoflavones therapeutic use, Non-alcoholic Fatty Liver Disease prevention & control, Phytoestrogens therapeutic use, Soy Foods
- Abstract
Obesity emerged as the major risk factor for metabolic syndrome. Postmenopausal women are more prone to develop obesity than premenopausal women. The absence of safe and effective conventional treatments for postmenopausal obesity has changed the focus to natural products as alternative remedy. We investigated the molecular basis of the effect of soy isoflavones (SIFs) on hypertriglyceridemia and hepatic steatosis in an animal model of postmenopausal obesity. Ovariectomized (OVX) and sham-operated Wistar rats were fed with high-fat diet (HFD) and normal diet for 8 weeks with and without SIF extract (150mg/kg body weight/day). Both OVX and HFD per se and when combined caused hypertriglyceridemia, hypercholesterolemia and atherogenic lipid profile. Proteomic studies revealed that both OVX and HFD caused overexpression of hepatic lipogenic proteins, such as LXR, SREBP1, PPARγ, ACC and FAS, in association with reduced expression of lipolytic proteins, such as FXR, PPARα, insig2 and SHP. Histological analysis showed fat accumulation and morphological abnormalities in the liver of OVX and HFD rats. All these metabolic derangements were further augmented when OVX was followed by HFD. In conclusion, these findings suggest that there was a synergism in the development of deranged lipid metabolism with the coexistence of postmenopausal state and the intake of fat-rich diet. SIF extract markedly alleviated the derangement of lipid metabolism suggesting the use of this natural phytoestrogen as a strategy for relieving dyslipidemia and hepatic steatosis associated with the postmenopausal women., (Copyright © 2016 Elsevier Inc. All rights reserved.)
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- 2016
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20. Curcumin inhibits hyperlipidemia and hepatic fat accumulation in high-fructose-fed male Wistar rats.
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Maithilikarpagaselvi N, Sridhar MG, Swaminathan RP, Sripradha R, and Badhe B
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- Animals, Body Weight drug effects, Body Weight physiology, Dietary Sucrose administration & dosage, Dietary Sucrose toxicity, Eating drug effects, Eating physiology, Fatty Liver chemically induced, Fatty Liver pathology, Fructose administration & dosage, Hyperlipidemias chemically induced, Hyperlipidemias pathology, Male, Rats, Rats, Wistar, Curcumin therapeutic use, Fatty Liver drug therapy, Fructose toxicity, Hyperlipidemias prevention & control
- Abstract
Context: Curcumin, an active principal of Curcuma longa Linn. (Zingiberaceae), has potent antioxidant and anti-inflammatory properties., Objectives: This study investigated the effects of curcumin on hyperlipidemia and hepatic steatosis in high-fructose-fed Wistar rats., Materials and Methods: Forty male Wistar rats were divided into four groups with 10 rats in each. Two groups were fed with standard rodent diet and the other two with 60% high-fructose diet for 10 weeks. Curcumin (200 mg/kg body weight) was administered along with the diets simultaneously to each of the aforementioned diet groups. After 10 weeks of experiment, blood samples were collected from tail vein. Liver, adipose and epididymal tissues were collected after sacrifice of the animals and stored for further analyses., Results: Administration of curcumin reduced body weight (280.6 ± 7.4 g), liver weight (2.5 ± 0.2 g/100 g BW), adipose weight (1.4 ± 0.3 g/100 g BW), plasma levels of TAG (86.1 ± 13.5 mg/dL), VLDL-C (17.2 ± 2.7 mg/dL), lipid ratios and increased HDL-C (28.4 ± 4.5 mg/dL) in fructose-fed rats. Curcumin supplementation significantly lowered TAG content and decreased the protein expression of LXR-α (43%) and SREBP1c (59%) in the liver. Furthermore, curcumin suppressed the expression of lipogenic enzymes, ACLY (95%), ACC (50%) and FAS (77%) in rats fed with high-fructose diet. No significant change was found in the expression of PPAR-α., Discussion and Conclusion: Curcumin prevented the high-fructose induced hyperlipidemia and hepatic steatosis.
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- 2016
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21. Predicting Severity of Acute Kidney Injury in Term Neonates with Perinatal Asphyxia Using Urinary Neutrophil Gelatinase Associated Lipocalin.
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Tanigasalam V, Bhat BV, Adhisivam B, Sridhar MG, and Harichandrakumar KT
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- Acute-Phase Proteins, Humans, Infant, Newborn, Lipocalins, Proto-Oncogene Proteins, Acute Kidney Injury diagnosis, Asphyxia, Biomarkers, Lipocalin-2 urine
- Abstract
Objective: To evaluate the utility of urinary Neutrophil Gelatinase Associated Lipocalin (NGAL) as a biomarker for predicting Acute Kidney Injury (AKI) and its severity among neonates with perinatal asphyxia., Methods: This descriptive study included 120 term neonates with perinatal asphyxia. Renal parameters of neonates were monitored and AKI was ascertained as per Acute Kidney Injury Network criteria. Urinary NGAL was estimated and correlated with severity of AKI., Results: Among the 120 neonates with perinatal asphyxia, 55(46 %) had AKI. The median urinary NGAL level was 165 ng/ml (88.8-245.8) in neonates with AKI compared to 58.97(42.8-74.7) in those without AKI. The median NGAL was 134.45(112.2-162.5), 301.2(255.5-361.2), 416.2(412.2-465.5) in AKI stages 1, 2 and 3 respectively. An NGAL cut off value of 86.82 ng/ml had 87 % sensitivity and 87.7 % specificity in predicting AKI., Conclusions: Urinary NGAL is a useful biomarker for predicting AKI and its severity among neonates with perinatal asphyxia.
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- 2016
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22. Association of Serum Vitamin D Levels with Bacterial Load in Pulmonary Tuberculosis Patients.
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Yuvaraj B, Sridhar MG, Kumar SV, and Kadhiravan T
- Abstract
Background: Vitamin D is known to have diverse effects on various systems in the body. There is evidence to suggest that a link exists between the serum vitamin D status and tuberculosis. The present study was designed to assess the alterations in serum 25-hydroxyvitamin D levels in newly diagnosed sputum acid fast bacilli (AFB) positive pulmonary tuberculosis patients and to study the association, if any, between serum vitamin D levels and different levels of sputum smear positivity., Methods: Serum 25-hydroxyvitamin D levels were estimated in 65 sputum AFB positive pulmonary tuberculosis patients and 65 age and gender-matched healthy controls., Results: The levels of serum 25 hydroxy-vitamin D in tuberculosis patients were not statistically different from the levels of serum 25 hydroxy-vitamin D in healthy controls. However, among patients with pulmonary tuberculosis, there was a significant negative correlation between the levels of serum 25 hydroxy-vitamin D and levels of sputum positivity., Conclusion: Serum vitamin D levels negatively correlates with bacterial load in patients with active pulmonary tuberculosis.
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- 2016
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23. Preventive effect of curcumin on inflammation, oxidative stress and insulin resistance in high-fat fed obese rats.
- Author
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Maithilikarpagaselvi N, Sridhar MG, Swaminathan RP, and Sripradha R
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- Adipose Tissue pathology, Animals, Blood Glucose analysis, Body Weight, Cholesterol blood, Curcumin administration & dosage, Diet, High-Fat adverse effects, Fasting blood, Inflammation blood, Inflammation drug therapy, Inflammation Mediators blood, Insulin blood, Liver metabolism, Liver pathology, Male, Muscle, Skeletal metabolism, Obesity etiology, Obesity pathology, Rats, Rats, Wistar, Triglycerides metabolism, Curcumin pharmacology, Dietary Supplements, Insulin Resistance physiology, Obesity therapy, Oxidative Stress physiology
- Abstract
Background: The present study investigated the beneficial effects of curcumin on inflammation, oxidative stress and insulin resistance in high-fat fed male Wistar rats., Methods: Five-month-old male Wistar rats (n=20) were divided into two groups (10 rats in each group). Among the two groups, one group received 30 % high-fat diet (HFD) and another group received 30 % HFD with curcumin (200 mg/kg body weight). Food intake, body weight and biochemical parameters were measured at the beginning and at the end of the study. After 10 weeks, oxidative stress parameters in skeletal muscle and hepatic triacylglycerol (TAG) content were estimated. Histological examinations of the liver samples were performed at the end of the experiment., Results: High-fat feeding caused increase in body weight, liver and adipose tissue mass. Rats fed with HFD showed increased levels of fasting plasma glucose, insulin, Homeostasis Model Assessment for Insulin resistance (HOMA-IR), total cholesterol (TC), TAG, very low density lipoprotein cholesterol (VLDL-c) and decreased high-density lipoprotein cholesterol (HDL-c). There was also increase in the plasma inflammatory markers [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP)] and skeletal muscle oxidative stress parameters [malondialdehyde (MDA), total oxidant status (TOS)] in these rats. In addition, high-fat feeding increased liver TAG content and caused fat accumulation in the liver. Treatment with curcumin significantly reduced body weight, relative organ weights (liver, adipose tissue), glucose, insulin and HOMA-IR. Curcumin supplementation decreased plasma levels of TC, TAG, VLDL-c, TNF-α and increased HDL-c. Administration of curcumin also reduced MDA, TOS in skeletal muscle, hepatic TAG content and liver fat deposition., Conclusions: Curcumin supplementation improved HFD-induced dyslipidemia, oxidative stress, inflammation and insulin resistance.
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- 2016
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24. Hydroxycitric acid ameliorates high-fructose-induced redox imbalance and activation of stress sensitive kinases in male Wistar rats.
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Sripradha R, Sridhar MG, and Maithilikarpagaselvi N
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- Animals, Antioxidants metabolism, Blood Glucose drug effects, Body Weight drug effects, Diet, Eating drug effects, Glucose Tolerance Test methods, Glutathione metabolism, Insulin blood, Insulin Resistance physiology, Lipid Peroxidation drug effects, Lipids blood, Liver drug effects, Liver metabolism, Male, Malondialdehyde metabolism, Plant Extracts pharmacology, Rats, Rats, Wistar, Triglycerides blood, Citrates pharmacology, Fructose pharmacology, Oxidation-Reduction drug effects, Oxidative Stress drug effects, Phosphotransferases metabolism
- Abstract
Background: Excess fructose consumption causes dyslipidemia, oxidative stress, and various complications. Hydroxycitric acid (HCA), one of the principal components of the fruit Garcinia cambogia, has been shown to possess antiobesity properties. The objective was to investigate the effects of HCA on redox imbalance and activation of stress sensitive kinases in high fructose-fed rats., Methods: Male Wistar rats (n=40) were randomly divided into four groups with 10 rats in each group. The rats were fed with either standard rodent diet or 60% fructose diet and administered with HCA at a dose of 400 mg/kg body wt/day for 10 weeks. Body weight was measured once a week, and food intake was noted daily. At the end of the study, lipid profile and oxidative stress parameters were estimated. Expressions of stress sensitive kinases were analyzed in liver homogenates., Results: Fructose-fed rats displayed elevated body weight, higher levels of plasma total cholesterol (TC), triacylglycerol (TAG), non-high-density lipoprotein cholesterol (non HDL-C), malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI), lower levels of HDL-C, glutathione (GSH), glutathione peroxidase (GPx), and total antioxidant status (TAS). Fructose feeding caused higher phosphorylation of stress sensitive kinases ERK ½ and p38. Administration with HCA lowered body weight, food intake, TAG, non-HDL-C, MDA, TOS, and OSI and elevated GSH, GPx, and TAS levels. Reduced phosphorylation of ERK ½ and p38 mitogen-activated protein kinase (MAPK) was observed upon HCA treatment., Conclusions: Thus, HCA improved fructose induced redox imbalance and activation of stress sensitive kinases through its hypolipidemic effects.
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- 2016
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25. Attenuated baroreflex sensitivity in normotensive prediabetes and diabetes in Indian adults.
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Keerthi GS, Pal P, Pal GK, Sahoo JP, Sridhar MG, and Balachander J
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- Adolescent, Adult, Baroreflex, Cardiovascular Diseases blood, Cardiovascular Diseases etiology, Diabetes Mellitus blood, Female, Humans, India, Male, Middle Aged, Prediabetic State blood, Prediabetic State complications, Young Adult, Cardiovascular Diseases physiopathology, Diabetes Mellitus physiopathology, Prediabetic State physiopathology
- Abstract
Purpose/aim of the Study: Though attenuated baroreflex sensitivity (BRS) is known to promote cardiovascular disease (CVD) risk in diabetics, its status in prediabetes has not been reported. Also, the link of BRS to CVD risk in normotensive diabetics has not been reported. This study aimed to evaluate the association of BRS to CVD risk in normotensive prediabetics and diabetics., Materials and Methods: Participants (n = 154) of 18-45 years were divided into normoglycemics (n = 52), prediabetics (n = 64) and diabetics (n = 38) based on American Diabetes Association criteria. Body mass index, waist-hip ratio, waist-height ratio, body fat mass index, basal heart rate, systolic blood pressure, diastolic blood pressure, rate pressure product, BRS, heart rate variability (HRV), fasting plasma glucose, fasting insulin, lipid profile and atherogenic index of plasma (AIP) were measured. Indian Diabetes Risk Score (IDRS) and homeostatic model assessment of insulin resistance were calculated., Results: There was significant increase in all the parameters except BRS, HRV and high-density lipoprotein in prediabetics and diabetics compared to normoglycemics. All these parameters were significantly altered in prediabetics compared to diabetics. Significant negative correlation was found between BRS and other parameters in prediabetics and diabetics., Conclusions: BRS was attenuated in normotensive prediabetics and diabetics with high IDRS, insulin resistance, AIP, dyslipidemia and reduced HRV that predisposes them to CVD risk. The study demonstrates CVD risk quite early in the prediabetics with reduced HRV, high body fat, hyperinsulinemia, insulin resistance, AIP and rate pressure product.
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- 2016
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26. Antihyperlipidemic and antioxidant activities of the ethanolic extract of Garcinia cambogia on high fat diet-fed rats.
- Author
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Sripradha R, Sridhar MG, and Maithilikarpagaselvi N
- Subjects
- Animals, Biomarkers metabolism, Cholesterol metabolism, Diet, High-Fat, Eating physiology, Male, Malondialdehyde metabolism, Oxidative Stress physiology, Phytotherapy methods, Rats, Wistar, Triglycerides metabolism, Antioxidants pharmacology, Ethanol pharmacology, Garcinia cambogia, Hyperlipidemias drug therapy, Hypolipidemic Agents pharmacology, Plant Extracts pharmacokinetics
- Abstract
Background: The study investigated the antihyperlipidemic and antioxidant activities of the ethanolic extract of Garcinia cambogia on high fat diet-fed rats., Methods: The phytochemical constituents, total polyphenol content and ferric reducing antioxidant power (FRAP) were estimated in the G. cambogia extract (GE). Male Wistar rats were fed with either standard rodent diet or 30% high-fat diet and administered with GE at a dose of 400 mg/kg body weight/day for 10 weeks. At the end, lipid profile and oxidative stress parameters were estimated., Results: The analyses revealed the presence of carbohydrates, proteins, sterols, tannins, flavonoids and saponins in GE. The total polyphenol content and FRAP of GE were 82.82±7.64 mg of gallic acid equivalents and 260.49±10.18 µM FRAP per gram of the GE. High-fat feeding elevated plasma total cholesterol (TC), triacylglycerol (TAG), non-high-density lipoprotein-cholesterol (non-HDL-C), malondialdehyde (MDA), reduced HDL-C and blood antioxidants, glutathione (GSH), glutathione peroxidase (GPx), catalase. Increase in total oxidant status (TOS), oxidative stress index (OSI) and decrease in the total antioxidant status (TAS) were observed in plasma, liver and kidney of fat-fed rats. Administration of GE decreased food intake, plasma TC, TAG, non HDL-C, MDA, increased HDL-C and blood antioxidants GSH, GPx, catalase. GE also reduced TOS, OSI and elevated TAS in plasma and liver of fat-fed rats. Renal OSI was significantly reduced upon GE treatment., Conclusions: Our study demonstrated that GE is effective in ameliorating high-fat-diet-induced hyperlipidemia and oxidative stress.
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- 2016
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27. Curcumin prevents inflammatory response, oxidative stress and insulin resistance in high fructose fed male Wistar rats: Potential role of serine kinases.
- Author
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Maithilikarpagaselvi N, Sridhar MG, Swaminathan RP, and Zachariah B
- Subjects
- Animals, Fructose administration & dosage, Glucose Intolerance prevention & control, Glucose Tolerance Test, Inflammation drug therapy, Male, Phosphorylation drug effects, Protein Serine-Threonine Kinases metabolism, Rats, Rats, Wistar, Structure-Activity Relationship, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Curcumin pharmacology, Fructose adverse effects, Inflammation prevention & control, Insulin Resistance, Oxidative Stress drug effects, Protein Serine-Threonine Kinases antagonists & inhibitors
- Abstract
Emerging evidence suggests that high fructose consumption may be a potentially important factor responsible for the rising incidence of insulin resistance and diabetes worldwide. The present study investigated the preventive effect of curcumin on inflammation, oxidative stress and insulin resistance in high fructose fed male Wistar rats at the molecular level. Fructose feeding for 10 weeks caused oxidative stress, inflammation and insulin resistance. Curcumin treatment attenuated the insulin resistance by decreasing IRS-1 serine phosphorylation and increasing IRS-1 tyrosine phosphorylation in the skeletal muscle of high fructose fed rats. It also attenuated hyperinsulinemia, glucose intolerance and HOMA-IR level. Curcumin administration lowered tumor necrosis factor alpha (TNF-α), C reactive protein (CRP) levels and downregulated the protein expression of cyclo-oxygenase 2 (COX-2), protein kinase theta (PKCθ). In addition, inhibitor κB alpha (IκBα) degradation was prevented by curcumin supplementation. Treatment with curcumin inhibited the rise of malondialdehyde (MDA), total oxidant status (TOS) and suppressed the protein expression of extracellular kinase ½ (ERK ½), p38 in the skeletal muscle of fructose fed rats. Further, it enhanced Glutathione Peroxidase (GPx) activity in the muscle of fructose fed rats. At the molecular level, curcumin inhibited the activation of stress sensitive kinases and inflammatory cascades. Our findings conclude that curcumin attenuated glucose intolerance and insulin resistance through its antioxidant and anti-inflammatory effects. Thus, we suggest the use of curcumin as a therapeutic adjuvant in the management of diabetes, obesity and their associated complications., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
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- 2016
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28. Decreased baroreflex sensitivity is linked to sympathovagal imbalance, low-grade inflammation, and oxidative stress in pregnancy-induced hypertension.
- Author
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Subha M, Pal P, Pal GK, Habeebullah S, Adithan C, and Sridhar MG
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- Adult, Biomarkers blood, Cytokines blood, Female, Humans, Hypertension, Pregnancy-Induced metabolism, Inflammation physiopathology, Pregnancy, Risk Factors, Baroreflex physiology, Blood Pressure physiology, Heart Rate physiology, Hypertension, Pregnancy-Induced physiopathology, Inflammation blood, Oxidative Stress, Vagus Nerve physiopathology
- Abstract
Pregnancy-induced hypertension (PIH) has been reported as a cardiovascular (CV) risk. We assessed the sympathovagal imbalance (SVI) and the association of inflammation and oxidative stress (OS) with CV risks in PIH. A total of 125 pregnant women having a risk factor for PIH were followed till term and the incidence of PIH was observed. Retrospectively, they were divided into two groups: Group I (those who did not develop PIH, n = 82) and Group II (those who developed PIH, n = 43). Blood pressure variability (BPV) parameters including baroreflex sensitivity (BRS), spectral heart rate variability (HRV), autonomic function tests (AFTs), inflammatory markers (interleukin-6, TNF-α, interferon-γ), and OS markers were measured in both the groups. Alterations in parasympathetic and sympathetic components of AFTs were analyzed. Link of various parameters to BRS was assessed by correlation and multiple regression analysis. Parasympathetic components of AFTs were decreased from the early part of pregnancy and sympathetic components were increased toward the later part of pregnancy. Decreased BRS, the marker of CV risk, was more prominent in Group II subjects. Independent contribution of interleukin-6 (β = 0.276, P = 0.020), TNF-α (β = 0.408, P = 0.002), interferon-γ (β = 0.355, P = 0.008), and thiobarbituric-acid reactive substance (β = 0.287, P = 0.015) to BRS was found to be significant. It was concluded that sympathetic overactivity that develops more in the later part (third trimester) of pregnancy contributes to SVI and genesis of PIH. In PIH women, CV risks are present from the beginning of pregnancy that intensifies in the later part of pregnancy. Retrograde inflammation and oxidative stress contribute to the decreased BRS in PIH.
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- 2016
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29. Does therapeutic hypothermia reduce acute kidney injury among term neonates with perinatal asphyxia?--a randomized controlled trial.
- Author
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Tanigasalam V, Bhat V, Adhisivam B, and Sridhar MG
- Subjects
- Adult, Female, Humans, Hypothermia, Induced adverse effects, Incidence, India, Infant, Newborn, Kidney Function Tests, Pregnancy, Acute Kidney Injury prevention & control, Asphyxia Neonatorum therapy, Hypothermia, Induced methods
- Abstract
Objective: The objective of this study is to evaluate whether therapeutic hypothermia reduces the incidence of acute kidney injury (AKI) among term neonates perinatal asphyxia., Methods: This randomized controlled trial conducted in a tertiary care teaching hospital, south India included 120 term neonates with perinatal asphyxia who were randomized to receive either therapeutic hypothermia or standard supportive care. Renal parameters of neonates in both the groups were monitored and AKI was ascertained as per Acute Kidney Injury Network criteria., Results: The incidence of AKI was less in therapeutic hypothermia group compared to standard treatment group (32% versus 60%, p < 0.05). The incidence of Stages 1, 2, and 3 AKI was 22%, 5%, and 5% in therapeutic hypothermia group compared with 52%, 5%, and 3%, respectively, in the standard treatment group. The mortality was less in therapeutic hypothermia group compared with the standard treatment group (26% versus 50%, p < 0.05)., Conclusion: Therapeutic hypothermia reduces the incidence and severity of AKI among term neonates with perinatal asphyxia.
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- 2016
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30. Periprocedural plasma fibrinogen levels and coronary stent outcome.
- Author
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Kavitha S, Sridhar MG, and Satheesh S
- Subjects
- Biomarkers blood, Coronary Angiography, Coronary Artery Disease diagnosis, Coronary Artery Disease surgery, Elective Surgical Procedures, Female, Follow-Up Studies, Humans, Incidence, India epidemiology, Male, Middle Aged, Postoperative Complications epidemiology, Retrospective Studies, Treatment Outcome, Coronary Artery Disease blood, Fibrinogen metabolism, Percutaneous Coronary Intervention adverse effects, Postoperative Complications blood, Stents adverse effects
- Abstract
Aim: Percutaneous intervention is one of the treatment option for coronary artery disease. Reinfarction and restenosis is one of the complication of the procedure. So this study was conducted to assess plasma fibrinogen levels pre- and post coronary stenting and its relation with outcome., Methods: After obtaining informed consent, venous blood samples were collected at three timed points in relation to stenting - 24h before, 24h after and 72h after stenting to assess fibrinogen levels. Patients were followed up for six months. Repeat revascularization, myocardial infarction and symptomatic angina were considered as major adverse clinical events., Results: 57 patients who underwent successful stenting and followed up for six months up were included in the study. Mean age was 53 years and 87.7% were males and 29.8% were diabetics. Baseline plasma fibrinogen level was significantly high in patients who developed repeat angina and myocardial infarction after the stenting [288.64±59.43 vs 393.75±32.97mg/dL, p=0.003] and it remained high during serial assessment [322.74±63.92 vs 422.00±55.28mg/dL, 326.23±65.81 vs 419.50±45.82mg/dL, 0.008, 0.012 respectively]. Patients who developed adverse events denied any drug default., Conclusion: We conclude that plasma fibrinogen plays a significant role in the development of adverse events following stenting shown by high level of plasma fibrinogen in patients who developed adverse events., (Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)
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- 2015
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31. Efficacy of Turmeric as Adjuvant Therapy in Type 2 Diabetic Patients.
- Author
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Maithili Karpaga Selvi N, Sridhar MG, Swaminathan RP, and Sripradha R
- Abstract
It is known that there is a significant interplay of insulin resistance, oxidative stress, dyslipidemia, and inflammation in type 2 diabetes mellitus (T2DM). The study was undertaken to investigate the effect of turmeric as an adjuvant to anti-diabetic therapy. Sixty diabetic subjects on metformin therapy were recruited and randomized into two groups (30 each). Group I received standard metformin treatment while group II was on standard metformin therapy with turmeric (2 g) supplements for 4 weeks. The biochemical parameters were assessed at the time of recruitment for study and after 4 weeks of treatment. Turmeric supplementation in metformin treated type 2 diabetic patient significantly decreased fasting glucose (95 ± 11.4 mg/dl, P < 0.001) and HbA1c levels (7.4 ± 0.9 %, P < 0.05). Turmeric administered group showed reduction in lipid peroxidation, MDA (0.51 ± 0.11 µmol/l, P < 0.05) and enhanced total antioxidant status (511 ± 70 µmol/l, P < 0.05). Turmeric also exhibited beneficial effects on dyslipidemia LDL cholesterol (113.2 ± 15.3 mg/dl, P < 0.01), non HDL cholesterol (138.3 ± 12.1 mg/dl, P < 0.05) and LDL/HDL ratio (3.01 ± 0.61, P < 0.01) and reduced inflammatory marker, hsCRP (3.4 ± 2.0 mg/dl, P < 0.05). Turmeric supplementation as an adjuvant to T2DM on metformin treatment had a beneficial effect on blood glucose, oxidative stress and inflammation.
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- 2015
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32. Amla prevents fructose-induced hepatic steatosis in ovariectomized rats: role of liver FXR and LXRα.
- Author
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Koshy SM, Bobby Z, Jacob SE, Ananthanarayanan PH, Sridhar MG, and Paulose DT
- Subjects
- Animals, Disease Models, Animal, Fatty Acid Synthases metabolism, Fatty Liver chemically induced, Female, Intracellular Signaling Peptides and Proteins analysis, Liver chemistry, Liver pathology, Liver X Receptors, Menopause, Organ Size drug effects, Orphan Nuclear Receptors analysis, Ovariectomy, Rats, Rats, Wistar, Receptors, Cytoplasmic and Nuclear analysis, Sterol Regulatory Element Binding Protein 1 analysis, Fatty Liver prevention & control, Fructose administration & dosage, Orphan Nuclear Receptors physiology, Phyllanthus emblica chemistry, Plant Extracts administration & dosage, Receptors, Cytoplasmic and Nuclear physiology
- Abstract
Objectives: Increased fructose consumption causes dyslipidemia and fatty liver in postmenopausal women, both independent risk factors for cardiovascular disease. This study explored the potential mechanisms by which amla (Emblica officinalis) reduced hypercholesterolemia and hypertriglyceridemia and prevented fatty liver in a fructose-fed, ovariectomized rat model of menopause., Methods: Sham-operated and ovariectomized rats were put on a chow or high fructose diet. They were further divided into groups with or without amla. After 18 weeks of treatment, livers were harvested and subjected to Western blot and histological analyses., Results: In all groups, amla increased the protein expression of liver farnesoid X receptor (FXR) and liver X receptor (LXR), key proteins involved in lipid metabolism. Fructose-fed rats developed fatty liver and amla prevented this. Here amla produced an exceptional rise in LXR and insulin-induced gene-2 (Insig-2) which prevented the maturation of sterol regulatory element-binding protein-1 and steroyl CoA desaturase-1, responsible for triglyceride synthesis. Amla also increased the protein expression of ATP binding cassette transporter A1 (ABCA1), involved in high density lipoprotein (HDL) synthesis as well as low density lipoprotein receptor (LDLR) responsible for uptake of LDL cholesterol. Besides this, amla increased the protein expression of peroxisome proliferator activated receptor α (PPARα) involved in β oxidation of fatty acids., Conclusions: Amla increased the protein expression of liver FXR, LXRα, PPARα and their downstream proteins Insig-2, ABCA1 and LDLR. This property of amla to modulate some of the key proteins involved in lipid metabolism promises its usefulness as a preventive agent for dyslipidemia and hepatic steatosis.
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- 2015
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33. Oxidative stress during alcohol withdrawal and its relationship with withdrawal severity.
- Author
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Parthasarathy R, Kattimani S, and Sridhar MG
- Abstract
Background: Oxidative parameters are altered during alcohol withdrawal and are said to contribute towards withdrawal symptoms in alcoholic patients., Aims: To study levels of five selected oxidative parameters during alcohol withdrawal state and after treatment of the withdrawal state and to assess the association of the oxidative parameters with the severity of alcohol withdrawal., Materials and Methods: This was a case-control study done in a De-addiction clinic of a tertiary teaching centre, Southern India. 50 persons having alcohol withdrawal symptoms were included. The oxidative stress parameters malondialdehyde, protein carbonyl, glutathione peroxidase, superoxide dismutase and catalase were assessed in during the withdrawal phase and again after the withdrawal had subsided. The same oxidative stress parameters were measured in the control group., Statistical Analysis: Statistical analysis was done using SPSS version 17.0. One way ANOVA and Pearson correlation test were used for finding the association between the oxidative stress parameters levels and the severity of alcohol withdrawal. Multiple linear regression analysis done to predict variables associated with level of oxidative parameters., Results: During alcohol withdrawal the pro-oxidant malondialdehyde was elevated compared to that in the control group. Among the antioxidant enzymes the superoxide dismutase was higher and catalase was lower than the control group levels. After remission of the alcohol withdrawal both malondialdehyde remained higher and superoxide dismutase lower than in the control group. The levels of oxidative stress parameters not correlated with the severity of alcohol withdrawal., Conclusions: oxidative stress parameters show changes during alcohol withdrawal and during the remission of withdrawal. However, levels of oxidative stress parameters not correlated with the severity of withdrawal.
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- 2015
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34. Amelioration of oxidative stress and insulin resistance by soy isoflavones (from Glycine max) in ovariectomized Wistar rats fed with high fat diet: the molecular mechanisms.
- Author
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Sankar P, Zachariah B, Vickneshwaran V, Jacob SE, and Sridhar MG
- Subjects
- Adipose Tissue metabolism, Animals, Antioxidants pharmacology, Diet, High-Fat, Female, Glucose Transporter Type 4 metabolism, Insulin blood, Liver metabolism, Ovariectomy, Rats, Rats, Wistar, Glycine max chemistry, Insulin Resistance, Isoflavones pharmacology, Oxidative Stress drug effects, Phytoestrogens pharmacology
- Abstract
Estrogen deficiency after menopause accelerates the redox imbalance and insulin signaling, leading to oxidative stress (OS) and insulin resistance (IR). The molecular mechanisms by which the loss of ovarian hormone leads to OS and IR remain unclear. In the present study we found that rats when subjected to ovariectomy (OVX) resulted in reduction of whole blood antioxidants and elevation of oxidant markers. The expression of anti-oxidant enzymes, superoxide dismutase (SOD1) and glutathione peroxidase (GPX1) was suppressed whereas the pro-oxidative enzyme NADPH oxidase (NOX4) and mitogen activated protein (MAP) kinases ERK 1/2 and p38 were increased at different tissues. Treatment with soy (SIF, 150 mg/kg BW for 12 weeks) extract markedly reversed these metabolic changes and improved OS. Ovariectomized rats also displayed glucose intolerance (GI) and IR as evident from the impaired glucose tolerance test, and reduced expression of adipose and hepatic insulin receptor beta (IRβ) and adipose tissue GLUT4. Treatment with SIF reversed the ovariectomy induced GI and IR. On the other hand, all these metabolic changes were further augmented when ovariectomy was followed by a high fat diet, and these changes were also reversed by SIF. Taken together, these findings emphasized the antioxidant property and anti-diabetic effects of soy isoflavones suggesting the use of this natural phytoestrogen as a strategy for relieving oxidative stress and insulin resistance in postmenopausal women., (Copyright © 2015. Published by Elsevier Inc.)
- Published
- 2015
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35. Curcumin Attenuates Oxidative Stress and Activation of Redox-Sensitive Kinases in High Fructose- and High-Fat-Fed Male Wistar Rats.
- Author
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Maithili Karpaga Selvi N, Sridhar MG, Swaminathan RP, and Sripradha R
- Abstract
The present study was carried out to investigate the effects of curcumin on oxidative stress and redox-sensitive kinases in high fructose- and high-fat-fed rats. Sixty rats were randomly divided into six groups with ten animals each. Rats were fed with a standard rodent diet, high fructose diet (60%), and high-fat diet (30%). Curcumin was administered to control, high fructose and high fat diet groups for ten weeks. At the end of the study, body weight and blood glucose levels were measured. The antioxidant enzymes GSH (reduced glutathione), GPx (glutathione peroxidase), and catalase activities were estimated in the blood. MDA, TAS, and TOS were estimated in the plasma, liver, and kidney. Curcumin treatment decreased body weight and blood glucose levels in the rats fed with fructose and high-fat diet. Antioxidant enzymes and plasma TAS were significantly improved by curcumin treatment in high fructose-fed rats, whereas in high-fat-fed rats, there was an increase only in the GPx activity. Curcumin significantly attenuated the elevation of plasma MDA and TOS in both diet groups. Hepatic MDA and TOS were found to be decreased upon curcumin supplementation in both diet groups, whereas a decrease in the renal MDA levels was observed only in fructose-treated rats, not in fat-fed rats. Curcumin treatment elevated liver TAS in rats fed only with the fructose-rich diet. Curcumin showed a significant decrease in the oxidative stress index (OSI) in plasma, liver, and kidney tissues in both diet groups. ERK phosphorylation was significantly decreased in both diet groups by curcumin treatment. Similarly, curcumin reduced the phosphorylation of p38 MAPK only in the high fructose-fed rats, not in the high-fat-fed rats. No significant changes were found in JNK phosphorylation in both diet groups. Thus, curcumin may be effective in the management of diet-induced oxidative stress and could be explored as a therapeutic adjuvant against complications associated with obesity and diabetes.
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- 2014
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36. Single nucleotide polymorphism of CYP3A5*3 contributes to clopidogrel resistance in coronary artery disease patients among Tamilian population.
- Author
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Priyadharsini R, Shewade DG, Subraja K, Ravindra BK, Umamaheswaran G, Dkhar SA, Satheesh S, Sridhar MG, Narayan SK, and Adithan C
- Subjects
- Clopidogrel, Humans, India, Pharmacogenetics methods, Platelet Aggregation genetics, Reverse Transcriptase Polymerase Chain Reaction, Coronary Artery Disease drug therapy, Coronary Artery Disease genetics, Cytochrome P-450 CYP3A genetics, Drug Resistance genetics, Ethnicity genetics, Polymorphism, Single Nucleotide genetics, Ticlopidine analogs & derivatives
- Abstract
Clopidogrel is an antiplatelet drug. It is used for the treatment as well as for the prophylaxis of coronary artery disease. Clopidogrel resistance is an emerging problem in clinical settings. The aim of the present study was to evaluate the effect of CYP3A5*3 genetic polymorphism on clopidogrel resistance. One hundred and forty-seven patients from outpatient Department of Cardiology on 75 mg/day of clopidogrel as maintenance dose were recruited from April 2010 to July 2011. All subjects gave written informed consent to participate in the study. DNA extraction was performed using phenol chloroform extraction procedure and genotyping by standard Taqman based RT-PCR method. Platelet aggregation was done at the end of 7th and 14th day by using chronolog lumi Aggregometer which is expressed as impedance in ohms. Impedance values of >5 ohms at the end of 6 min were considered as clopidogrel resistance. Subjects (N = 147) were analysed for CYP3A5*3 polymorphism, of which 49 (33%) were found to be clopidogrel resistant. Homomutants of CYP3A5*3 gene had 2.78 (0.97-7.98; p < 0.05) fold risk and heteromutants had 2.4 (0.93-6.46; p < 0.05) fold risk of developing clopidogrel resistance. Carriers of defective allele G of CYP3A5*3 had higher propensity to cause clopidogrel resistance with an odds ratio of 1.63. Variant alleles and genotypes of CYP3A5*3 polymorphism contributed significantly to clopidogrel resistance with a higher odds ratio. Thus, pharmacogenomics paves way for the emergence of stratified medicine in clopidogrel therapy and personalised pharmacotherapy in ischaemic heart disease.
- Published
- 2014
- Full Text
- View/download PDF
37. Adiponectin-resistin index and its strong association with acute coronary syndrome in South Indian men.
- Author
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Singh P, Sridhar MG, Rajappa M, Balachander J, and Kadhiravan T
- Subjects
- Acute Coronary Syndrome epidemiology, Adult, Blood Glucose analysis, Cross-Sectional Studies, Humans, India epidemiology, Insulin, Insulin Resistance, Interleukin-6 blood, Male, Middle Aged, Acute Coronary Syndrome blood, Adiponectin blood, Resistin blood
- Abstract
Background: India has the highest burden of acute coronary syndromes worldwide. Apart from certain lipid alterations that have been established to be definite risk factors, low level of adiponectin, high levels of resistin, and IL-6 have been shown to be risk factors for cardiovascular events. Insulin resistance is also a significant predictor of poor outcome in patients admitted with ACS., Methods: 69 male patients with ACS and 70 age-matched healthy males were recruited in the study. Insulin, total adiponectin, resistin, and IL-6 levels were assayed in all study subjects. Indices of insulin resistance and novel adipokine indices were calculated using standard formulae. Multiple logistic regression analysis was done to find out the best predictor of ACS., Results: Resistin, IL-6, insulin resistance indices, AR index, and IRAR index were found to be significantly higher, while insulin sensitivity indices and total adiponectin were found to be lower in cases, as compared with controls (p < 0.001). Insulin resistance was found to be higher in the admission sample, when compared to the fasting sample in patients with ACS (p = 0.01). On multivariate logistic regression analysis, HOMA-IR and AR index were found to be significantly associated with ACS. AR index was the best independent predictor of ACS, with the highest odds ratio (AR index: adjusted OR 17.528, p < 0.0001 versus HOMA-IR: adjusted OR 1.146, p = 0.001)., Conclusions: The present results implicate that adipokines are significantly associated with pathogenesis of ACS, warranting adequate and early appropriate treatment to reverse this metabolic dysregulation. In our study, AR index was the best predictor of ACS. Hence, the novel AR index might be useful in routine clinical practice for screening persons with increased risk of future development of ACS.
- Published
- 2014
- Full Text
- View/download PDF
38. Lipoprotein ratios as surrogate markers for insulin resistance in South indians with normoglycemic nondiabetic acute coronary syndrome.
- Author
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Rajappa M, Sridhar MG, Balachander J, Sethuraman KR, and Rajendiran KS
- Abstract
Background. Insulin resistance has been associated with dyslipidemia and cardiovascular disease. Even though homeostasis model assessment of insulin resistance (HOMA-IR) is a well-known insulin resistance predictor, estimation of serum lipoprotein ratios has been recently suggested as a surrogate marker for insulin resistance. Here, we evaluated the relationship between lipoprotein ratios and insulin resistance in normoglycemic nondiabetic south Indians with acute coronary syndrome. Methods. 100 normoglycemic nondiabetic ACS patients and 140 controls were enrolled in the study. Levels of fasting glucose, fasting insulin, and lipid profile [total cholesterol (TC), triglycerides (TG), and high density lipoprotein cholesterol (HDL-C)], lipoprotein(a) [Lp(a)] levels were measured and lipoprotein ratios were computed. HOMA-IR was used to calculate the insulin resistance. Receiver operating characteristic curves (ROC) analysis was used to compare the power of these lipoprotein ratios to predict insulin resistance. Results. Lipoprotein ratios were significantly higher in normoglycemic nondiabetic ACS patients, as compared to healthy controls, and were significantly correlated with HOMA-IR by Spearman's rank correlation analysis. ROC curve showed that Lp(a)/HDL-C and TG/HDL-C ratios were the best surrogate predictors of insulin resistance in normoglycemic nondiabetic ACS. Conclusion. This study demonstrates that serum lipoprotein ratios significantly correlate with insulin resistance in normoglycemic nondiabetic ACS. Lp(a)/HDL-C and TG/HDL-C ratios could be used as surrogate markers of insulin resistance in atherosclerosis-prone south Indians with normoglycemic nondiabetic ACS.
- Published
- 2014
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39. A Randomized Controlled Trial to Study the Effect of Yoga Therapy on Cardiac Function and N Terminal Pro BNP in Heart Failure.
- Author
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Krishna BH, Pal P, Pal G, Balachander J, Jayasettiaseelon E, Sreekanth Y, Sridhar M, and Gaur G
- Abstract
Aims: The purpose of this study was to evaluate whether yoga training in addition to standard medical therapy can improve cardiac function and reduce N terminal pro B-type natriuretic peptide (NT pro BNP) in heart failure (HF)., Methods: 130 patients were recruited and randomized into two groups: Control Group (CG) (n = 65), Yoga Group (YG). In YG, 44 patients and in CG, 48 patients completed the study. Cardiac function using left ventricular ejection fraction (LVEF), myocardial performance index (Tei index), and NT pro BNP, a biomarker of HF, was assessed at baseline and after 12 weeks., Result: Improvement in LVEF, Tei index, and NT pro BNP were statistically significant in both the groups. Furthermore, when the changes in before and after 12 weeks were in percentage, LVEF increased 36.88% in the YG and 16.9% in the CG, Tei index was reduced 27.87% in the YG and 2.79% in the CG, NT pro BNP was reduced 63.75% in the YG and 10.77% in the CG. The between group comparisons from pre to post 12 weeks were significant for YG improvements (LVEF, P < 0.01, Tei index, P < 0.01, NT pro BNP, P < 0.01)., Conclusion: These results indicate that the addition of yoga therapy to standard medical therapy for HF patients has a markedly better effect on cardiac function and reduced myocardial stress measured using NT pro BNP in patients with stable HF.
- Published
- 2014
- Full Text
- View/download PDF
40. Identification of mistakes and their correction by a small group discussion as a revision exercise at the end of a teaching module in biochemistry.
- Author
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Bobby Z, Nandeesha H, Sridhar MG, Soundravally R, Setiya S, Babu MS, and Niranjan G
- Subjects
- Humans, Biochemistry education, Education, Medical, Graduate
- Abstract
Background: Graduate medical students often get less opportunity for clarifying their doubts and to reinforce their concepts after lecture classes. The Medical Council of India (MCI) encourages group discussions among students. We evaluated the effect of identifying mistakes in a given set of wrong statements and their correction by a small group discussion by graduate medical students as a revision exercise., Methods: At the end of a module, a pre-test consisting of multiple-choice questions (MCQs) was conducted. Later, a set of incorrect statements related to the topic was given to the students and they were asked to identify the mistakes and correct them in a small group discussion. The effects on low, medium and high achievers were evaluated by a post-test and delayed post-tests with the same set of MCQs., Results: The mean post-test marks were significantly higher among all the three groups compared to the pre-test marks. The gain from the small group discussion was equal among low, medium and high achievers. The gain from the exercise was retained among low, medium and high achievers after 15 days., Conclusion: Identification of mistakes in statements and their correction by a small group discussion is an effective, but unconventional revision exercise in biochemistry., (Copyright 2014, NMJI.)
- Published
- 2014
41. Revisiting the role of first trimester homocysteine as an index of maternal and fetal outcome.
- Author
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Mascarenhas M, Habeebullah S, and Sridhar MG
- Subjects
- Adult, Amniotic Fluid, Cohort Studies, Female, Humans, Infant, Low Birth Weight, Meconium, Pregnancy, Prospective Studies, Young Adult, Abortion, Spontaneous blood, Diabetes, Gestational blood, Homocysteine blood, Hypertension, Pregnancy-Induced blood, Oligohydramnios blood, Pregnancy Trimester, First blood
- Abstract
AIM. To revisit the role of first trimester homocysteine levels with the maternal and fetal outcome. METHODS. This was a cohort study comprising 100 antenatal women between 8 and 12 weeks of gestation. Serum homocysteine levels were checked after overnight fasting. RESULTS. There were significantly elevated homocysteine levels among women with prior history of hypertensive disorders of pregnancy and prior second or third trimester pregnancy losses. There was no significant difference in homocysteine levels among women with previous gestational diabetes mellitus, preterm deliveries, or fetal malformations. Homocysteine levels were significantly elevated in those who developed hypertensive disorder of pregnancy, oligohydramnios, and meconium stained amniotic fluid, had a pregnancy loss, or delivered a low birth weight baby. There was no significant difference in homocysteine levels for those who developed gestational diabetes mellitus. CONCLUSIONS. Increased first trimester serum homocysteine is associated with history of pregnancy losses, hypertensive disorders of pregnancy, and preterm birth. This is also associated with hypertensive disorders of pregnancy, pregnancy loss, oligohydramnios, meconium stained amniotic fluid, and low birth weight in the current pregnancy. This trial is registered with ClinicalTrials.gov CTRI/2013/02/003441.
- Published
- 2014
- Full Text
- View/download PDF
42. Genetic polymorphisms of CYP2C19 influences the response to clopidogrel in ischemic heart disease patients in the South Indian Tamilian population.
- Author
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Subraja K, Dkhar SA, Priyadharsini R, Ravindra BK, Shewade DG, Satheesh S, Sridhar MG, Narayan SK, and Adithan C
- Subjects
- Adult, Aged, Chi-Square Distribution, Clopidogrel, Cytochrome P-450 CYP2C19, Female, Gene Frequency, Genotype, Humans, India epidemiology, Linear Models, Male, Middle Aged, Multivariate Analysis, Myocardial Ischemia ethnology, Pharmacogenetics, Phenotype, Platelet Aggregation Inhibitors adverse effects, Platelet Aggregation Inhibitors metabolism, Polymerase Chain Reaction, Precision Medicine, Risk Factors, Ticlopidine adverse effects, Ticlopidine metabolism, Ticlopidine therapeutic use, Treatment Outcome, Aryl Hydrocarbon Hydroxylases genetics, Myocardial Ischemia drug therapy, Platelet Aggregation drug effects, Platelet Aggregation Inhibitors therapeutic use, Polymorphism, Genetic, Ticlopidine analogs & derivatives
- Abstract
Background: The antiplatelet activity of clopidogrel is variable among patients suffering from ischemic heart disease. Variation in the cytochrome P450 2C19 (CYP2C19) gene coding for the CYP2C19 enzyme is one of the major determinants of this variable response to clopidogrel. The activity of the CYP2C19 enzyme, which plays a role in the conversion of the prodrug clopidogrel to its active metabolite, is genetically influenced by polymorphisms in its gene. The aim of our study was to evaluate the association of CYP2C19 polymorphisms and the antiplatelet effect of clopidogrel in the South Indian Tamilian population., Materials and Methods: Genotyping and platelet aggregation results of 149 ischemic heart disease patients on clopidogrel maintenance therapy (75 mg daily dose) were analyzed in this study. CYP2C19 polymorphisms were genotyped by the PCR-restriction fragment length polymorphism method. We measured residual platelet activities in these patients on clopidogrel therapy in terms of impedance (expressed as ohms). The study subjects were divided into two metabolizer phenotype groups [group 1: poor/intermediate metabolizers (PM/IM); group 2: extensive/ultra-rapid metabolizers (EM/URM)] based on CYP2C19 genotype, and the residual platelet activities were compared. Higher values of impedance denote increased residual platelet activity., Results: Poor/intermediate metabolizers had significantly higher impedance values than EM/URM [(median; range) 4.0; 0-13 vs. 2.0; 0-11, respectively; p = 0.04]. These higher impedance values denote higher residual platelet activities among the carriers of loss-of-function alleles (CYP2C19*2,*3) than among non-carriers. However, residual platelet activities were lower among the carriers of the gain-of-function allele (CYP2C19*17) than among non-carriers, although this difference was not significant., Conclusion: Patients with CYP2C19 (*2 or *3) genetic polymorphisms had higher residual platelet activities and were associated with a reduced antiplatelet response to clopidogrel. As the South Indian Tamilian population is characterized with higher frequencies of these genetic polymorphisms, our findings mandate further studies aimed at initiating genome-based personalized antiplatelet therapy.
- Published
- 2013
- Full Text
- View/download PDF
43. Levels of non enzymatic antioxidants in Down syndrome.
- Author
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Sulthana SM, Kumar SN, Sridhar MG, Bhat BV, and Rao KR
- Subjects
- Biomarkers blood, Case-Control Studies, Child, Child, Preschool, Down Syndrome diagnosis, Down Syndrome metabolism, Female, Humans, Infant, Infant, Newborn, Male, Antioxidants metabolism, Down Syndrome blood, Glutathione blood, Oxidative Stress
- Abstract
Objectives: To confirm the clinical diagnosis of Down syndrome by chromosomal analysis and to explore the oxidative stress in children with Down syndrome by estimating the levels of non enzymatic antioxidants like reduced glutathione(GSH) and total antioxidants status (TAS)., Methods: The study included 31 clinically diagnosed children with Down syndrome with equal number of age and sex matched controls. Trisomy 21 was confirmed by conventional lymphocyte cell culture. Erythrocytic reduced glutathione (GSH) and plasma total antioxidant status (TAS) were measured sphectrophotometrically., Results: The levels of erythrocytic reduced glutathione (GSH) and plasma total antioxidant status (TAS) were significantly reduced in children with Down syndrome., Conclusions: Children with Down syndrome have elevated levels of oxidative stress . Hence antioxidant therapy can be beneficial among them.
- Published
- 2012
- Full Text
- View/download PDF
44. Can protein carbonyl/glutathione ratio be used as a potential biomarker to assess oxidative stress in alcoholic hepatitis?
- Author
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Sripradha R, Sridhar MG, and Agrawal A
- Subjects
- Adult, Biomarkers blood, Humans, Male, Middle Aged, Glutathione blood, Hepatitis, Alcoholic blood, Oxidative Stress, Protein Carbonylation physiology
- Abstract
Context: Oxidative stress plays a crucial role in the pathogenesis of alcoholic liver disease (ALD)., Aim: The present study was undertaken to evaluate the significance of protein carbonyl/glutathione ratio as a biomarker to assess the oxidative stress in alcoholic hepatitis., Settings and Design: The study included 30 patients with alcoholic hepatitis and 30 age-sex- matched controls. Protein carbonyl (PCO) levels was estimated by modified levine's method, malondialdehyde (MDA) by thiobarbituric acid method, reduced glutathione (GSH) by dithiobis-2-nitrobenzoic acid method, total sialic acid (TSA) by modified aminoff's method, plasma transferases (GGT, AST, and ALT), total protein and albumin using commercial kits adapted to autoanalyzer respectively., Statistical Analysis Used: All data were expressed as mean ± SEM. Spearman's correlation analysis and receiver operating characteristic curve were performed using SPSS version 16 for Microsoft. A P value < 0.05 was considered as significant., Results: Alcoholic hepatitis patients showed significantly higher levels of PCO, MDA, GGT, AST, AST/ALT, TSA, and significantly lower GSH, total protein and albumin levels. PCO/GSH ratio in these patients showed a significant positive correlation with GGT (r = 0.594, P = 0.000), AST/ALT (r = 0.443 P = 0.000), MDA (r = 0.727, P = 0.000), TSA (r = 0.729, P = 0.000), and a significant negative correlation with total protein (r = -0.683, P = 0.000) and albumin (r = -0.544, P = 0.000). ROC curve showed a cut off value of 2.735, indicating 100% sensitivity and 90% specificity of PCO/GSH at this value., Conclusions: Alcohol intake regularly for long duration leads to oxidative stress. We suggest that PCO/GSH ratio can be used as a potential biomarker to assess oxidative stress in alcoholic hepatitis.
- Published
- 2010
45. Changes in GH/IGF-1 axis in intrauterine growth retardation: consequences of fetal programming?
- Author
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Setia S and Sridhar MG
- Subjects
- Animals, Female, Fetal Growth Retardation genetics, Fetus metabolism, Human Growth Hormone genetics, Humans, Insulin-Like Growth Factor I genetics, Male, Pregnancy, Fetal Development, Fetal Growth Retardation metabolism, Human Growth Hormone metabolism, Insulin-Like Growth Factor I metabolism, Maternal-Fetal Exchange
- Abstract
Fetal growth is a complex process that depends on the genotype and epigenotype of the fetus, maternal nutrition, the availability of nutrients and oxygen to the fetus, intrauterine insults, and a variety of growth factors and proteins of maternal and fetal/placental origin. In the fetus, growth hormone (GH) plays little or no role in regulating fetal growth, and insulin-like growth factors (IGFs) control growth directly independent of fetal GH secretion. Placental growth hormone (PGH) is the prime regulator of maternal serum IGF-1 during pregnancy. Total as well as free PGH and IGFs are significantly lower in pregnancies with intrauterine growth retardation (IUGR). The GH/IGF axis is significantly affected by intrauterine growth retardation and some of these alterations may lead to permanent pathological programming of the IGF axis. Alterations in the IGF axis may play a role in the future occurrence of insulin resistance and hypertension. In this review we focus on the regulation of fetal growth and the role of fetal programming in the late consequences of a poor fetal environment reflected in IUGR.
- Published
- 2009
- Full Text
- View/download PDF
46. Electrocardiographic and echocardiographic changes in perinatal asphyxia.
- Author
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Rajakumar PS, Vishnu Bhat B, Sridhar MG, Balachander J, Konar BC, Narayanan P, and Chetan G
- Subjects
- Cardiomyopathies blood, Cardiomyopathies diagnosis, Case-Control Studies, Echocardiography, Electrocardiography, Female, Humans, Incidence, Infant, Newborn, Length of Stay, Prospective Studies, Sensitivity and Specificity, Asphyxia Neonatorum complications, Cardiomyopathies etiology, Creatine Kinase, MB Form blood, Myocardium enzymology, Troponin T blood
- Abstract
Objective: To study the usefulness of cardiac enzymes in evaluating myocardial damage in perinatal asphyxia., Methods: Thirty term babies with perinatal asphyxia and without any congenital malformations were selected as cases. They were compared with thirty healthy term babies without asphyxia. Myocardial dysfunction was evaluated using clinical, electrocardiography, echocardiography and cardiac enzymes i.e, troponin-T and CK-MB levels., Results: Among the 30 cases 23 had evidence of myocardial involvement while one baby in the control group had ECG evidence compatible with cardiac involvement. Cardiac enzymes were significantly increased in babies with perinatal asphyxia. The mean level of C-troponin-T among cases and controls were 0.22+/-0.28 and 0.003+/-0.018 while CK-MB levels were 121+/-77.4 IU/L and 28.8 +/- 20.2 IU/L respectively. C-troponin-T had higher sensitivity and specificity compared to CK-MB levels. Moreover, C troponin-T levels correlated well with severity and outcome in babies with perinatal asphyxia., Conclusion: C-Tropopnin assay is useful in evaluating the severity of myocardial damage and outcome in perinatal asphyxia.
- Published
- 2009
- Full Text
- View/download PDF
47. Cardiac enzyme levels in myocardial dysfunction in newborns with perinatal asphyxia.
- Author
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Rajakumar PS, Bhat BV, Sridhar MG, Balachander J, Konar BC, Narayanan P, and Chetan G
- Subjects
- Humans, Infant, Newborn, Prospective Studies, Sensitivity and Specificity, Asphyxia Neonatorum complications, Cardiomyopathies diagnosis, Cardiomyopathies etiology, Creatine Kinase, MB Form blood, Myocardium enzymology, Troponin T blood
- Abstract
Objective: To study the usefulness of cardiac enzymes in evaluating myocardial damage in perinatal asphyxia., Methods: Thirty term babies with perinatal asphyxia and without any congenital malformations were selected as cases. They were compared with thirty healthy term babies without asphyxia. Myocardial dysfunction was evaluated using clinical, electrocardiography, echocardiography and cardiac enzymes i.e, troponin-T and CK-MB levels., Results: Among the 30 cases 23 had evidence of myocardial involvement while one baby in the control group had ECG evidence compatible with cardiac involvement. Cardiac enzymes were significantly increased in babies with perinatal asphyxia. The mean level of C-troponin-T among cases and controls were 0.22+/-0.28 and 0.003+/-0.018 while CK-MB levels were 121+/-77.4 IU/L and 28.8 +/- 20.2 IU/L respectively. C-troponin-T had higher sensitivity and specificity compared to CK-MB levels. Moreover, C troponin-T levels correlated well with severity and outcome in babies with perinatal asphyxia., Conclusion: C-Tropopnin assay is useful in evaluating the severity of myocardial damage and outcome in perinatal asphyxia.
- Published
- 2008
- Full Text
- View/download PDF
48. Formulation of questions followed by small group discussion: a learning method for medical students.
- Author
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Bobby Z, Nandeesha H, Sridhar MG, Koner BC, Renuka P, Setiya S, Kumaran SS, and Mawlong A
- Subjects
- Group Processes, Humans, India, Education, Medical, Undergraduate methods, Learning, Students, Medical, Teaching
- Published
- 2008
49. Is euthyroid sick syndrome a defensive mechanism against oxidative stress?
- Author
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Selvaraj N, Bobby Z, and Sridhar MG
- Subjects
- Energy Metabolism physiology, Euthyroid Sick Syndromes metabolism, Glutathione metabolism, Humans, Selenium metabolism, Euthyroid Sick Syndromes etiology, Glutathione Peroxidase metabolism, Iodide Peroxidase metabolism, Oxidative Stress physiology
- Abstract
The body has a hierarchy of defence strategies to deal with oxidative stress. Among these arrays of defence mechanisms, the over expression and increased activity of glutathione peroxidases has been suggested as the first line of defence. The two main cofactors required for glutathione peroxidase activity are selenium and reduced glutathione. These two factors have been shown to be required for the deiodinase activity also. In vitro and in vivo studies have shown that oxidative stress decreases the activity of deiodinase. Thus, a decrease in deiodinase activity would facilitate the use of these cofactors by glutathione peroxidase in combating oxidative stress. Lowering of serum T3 is generally regarded as a valuable calorie-sparing economy. A decreased metabolic state of the cells as found in euthyroid sick syndrome indicates a decreased free radical generation from the mitochondria. For this reason, euthyroid sick syndrome could be considered as a physiological mechanism activated in response to oxidative stress.
- Published
- 2008
- Full Text
- View/download PDF
50. Oxidative stress induced changes in plasma protein can be a predictor of imminent severe dengue infection.
- Author
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Soundravally R, Sankar P, Hoti SL, Selvaraj N, Bobby Z, and Sridhar MG
- Subjects
- Adult, Analysis of Variance, Case-Control Studies, Female, Hospitalization, Humans, Linear Models, Male, Middle Aged, Protein Carbonylation, ROC Curve, Sensitivity and Specificity, Spectrophotometry, Blood Proteins chemistry, Dengue diagnosis, Oxidative Stress
- Abstract
Objectives: Oxidative stress in dengue viral infection has been suggested and severity of it was found to be associated with progress of illness. Hence assessing oxidative stress mediated changes in plasma proteins can be an early biomarker for prediction of severe dengue infection., Design and Methods: Thirty two dengue hemorrhagic fever (DHF), 21 dengue shock syndrome (DSS), 27 dengue fever (DF) and 63 age and sex matched controls, were included in this study. Blood samples were collected on the 3rd day of fever. Protein carbonylation (PCOs) and protein-bound sulphydryl (PBSH) group levels were determined by spectrophotometric method and analyzed as predictor of dengue hemorrhagic fever and dengue shock syndrome., Results: About 80-84% of cases presented with no signs of DHF/DSS at the time of sampling. Dengue infected individuals had significantly elevated PCOs and low PBSH group levels than the controls. Using one-way ANOVA we found a significant difference with high PCOs and low PBSH group levels between DHF and DSS when compared with DF (P<0.001). However, no difference was observed in PBSH group levels between DHF and DSS. A significant difference in PCOs to PBSH ratio was observed among DF, DHF and DSS (P<0.001). Linear regression analysis revealed that duration of hospitalization is dependent on PCOs and PBSH group levels. Receiver operator curve (ROC) analysis indicated that 5.22nmol/mg protein PCOs; 1.08 PCOs to PBSH group levels ratio were optimal cutoff value for predicting DHF with sensitivity and specificity of 87.5% and 74.1%; 96.9% and 81.5%, respectively. For DSS prediction, 6.13 nmol/mg protein PCOs; 1.16 PCOs to PBSH group levels ratio were found as effective cutoff with sensitivity and specificity of 81% and 71.9%; 95.2% and 56.2%, respectively., Conclusion: Oxidative stress has been observed to develop since early days of onset of dengue infection. Plasma PCOs, PCOs to PBSH group ratio were found to very well predict DHF/DSS.
- Published
- 2008
- Full Text
- View/download PDF
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