Irisin and Visfatin Predicts Severity of Diabetic Nephropathy.

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.

Exploring circulatory shock and mortality in viper envenomation: a prospective observational study from India.

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.

CA 125 is a better marker to differentiate endometrial cancer and abnormal uterine bleeding.

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.

The Serological and Biochemical Markers of Adrenal Cortex and Endocrine Pancreas Dysfunction in Patients with Hashimoto's Thyroiditis: A Hospital-based Pilot Study.

BACKGROUND: The prevalence of both islet cell and adrenal autoimmunity among Asian Indian hypothyroidism patients with Hashimoto's thyroiditis (HT) is lacking in literature. OBJECTIVES: The objective of this study was to assess the proportion of Addison's disease (AD) and type 1 diabetes mellitus (T1DM) in patients with HT. MATERIALS AND METHODS: The patients with hypothyroidism due to HT were included in this study over 2 years. Primary hypothyroidism was defined as high serum thyroid-stimulating hormone (>5.5 mIU/L) with or without low thyroxine level. HT was defined by the presence of high thyroid peroxidase antibody (Ab) titer (>35 IU/ml). Autoimmune markers of AD and T1DM, i.e., adrenal (21-hydroxylase) Ab, glutamic acid decarboxylase (GAD) Ab, and insulinoma-associated antigen-2 (IA-2) Ab were measured among them. In addition, 250 µg adrenocorticotropic hormone (ACTH) stimulation test was done in patients with adrenal Ab. Similarly, beta cell function was assessed in patients with GAD and/or IA-2 Ab. RESULTS: Out of 150 patients screened, 136 patients were included in this study. Seven patients had adrenal Ab while 15 had IA-2 Ab. The GAD Ab was not present in any of the patients in the study. ACTH stimulation test was done in four of seven patients with adrenal Ab and beta cell function was assessed in 8 of 15 patients with islet cell Ab. All patients with adrenal Ab had normal adrenal function and 1 out of 15 with IA-2 Ab developed diabetes mellitus during follow-up. CONCLUSIONS: Either adrenal or islet cell Ab was found in 16% Asian Indian hypothyroidism patients with HT.

An exploratory study of immune markers in acute and transient psychosis.

The aim of this study was to look into the balance of pro-inflammatory (TNF-α, IL-6) and anti-inflammatory (TGF-ß) 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-ß (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-ß (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-ß (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.

Insulin Plant (Costus pictus) Extract Restores Thyroid Hormone Levels in Experimental Hypothyroidism.

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.

Decreased baroreflex sensitivity is linked to sympathovagal imbalance, low-grade inflammation, and oxidative stress in pregnancy-induced hypertension.

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 (ß = 0.276, P = 0.020), TNF-α (ß = 0.408, P = 0.002), interferon-γ (ß = 0.355, P = 0.008), and thiobarbituric-acid reactive substance (ß = 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.

Association of Serum Vitamin D Levels with Bacterial Load in Pulmonary Tuberculosis Patients.

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.

Does therapeutic hypothermia reduce acute kidney injury among term neonates with perinatal asphyxia?--a randomized controlled trial.

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.

Periprocedural plasma fibrinogen levels and coronary stent outcome.

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.

Oxidative stress during alcohol withdrawal and its relationship with withdrawal severity.

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.

Efficacy of Turmeric as Adjuvant Therapy in Type 2 Diabetic Patients.

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.

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.

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 (IRß) 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.

Amla prevents fructose-induced hepatic steatosis in ovariectomized rats: role of liver FXR and LXRα.

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 ß 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.

Identification of mistakes and their correction by a small group discussion as a revision exercise at the end of a teaching module in biochemistry.

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.

Adiponectin-resistin index and its strong association with acute coronary syndrome in South Indian men.

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.

Lipoprotein ratios as surrogate markers for insulin resistance in South indians with normoglycemic nondiabetic acute coronary syndrome.

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.

Revisiting the role of first trimester homocysteine as an index of maternal and fetal outcome.

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.

Genetic polymorphisms of CYP2C19 influences the response to clopidogrel in ischemic heart disease patients in the South Indian Tamilian population.

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.

Levels of non enzymatic antioxidants in Down syndrome.

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.