Exploring faculty perspectives on competency-based medical education: A report from India.

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.

Role of Zinc in Neonatal Sepsis.

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.

Effect of zinc supplementation on relative expression of immune response genes in neonates with sepsis: A preliminary study.

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.

Evaluation of Serum Vitamin D Levels in Diabetic Foot Infections: A Cross-Sectional Study in a Tertiary Care Center in South India.

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.

Clomiphene citrate increases nitric oxide, interleukin-10 and reduces matrix metalloproteinase-9 in women with polycystic ovary syndrome.

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.

Short Term Oral Zinc Supplementation among Babies with Neonatal Sepsis for Reducing Mortality and Improving Outcome - A Double-Blind Randomized Controlled Trial.

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.

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.

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.

Efficacy of zinc supplementation on serum calprotectin, inflammatory cytokines and outcome in neonatal sepsis - a randomized controlled trial.

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.

Soy isoflavones (Glycine max) ameliorate hypertriglyceridemia and hepatic steatosis in high fat-fed ovariectomized Wistar rats (an experimental model of postmenopausal obesity).

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.

Curcumin inhibits hyperlipidemia and hepatic fat accumulation in high-fructose-fed male Wistar rats.

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.

Predicting Severity of Acute Kidney Injury in Term Neonates with Perinatal Asphyxia Using Urinary Neutrophil Gelatinase Associated Lipocalin.

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.

Hydroxycitric acid ameliorates high-fructose-induced redox imbalance and activation of stress sensitive kinases in male Wistar rats.

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.

Preventive effect of curcumin on inflammation, oxidative stress and insulin resistance in high-fat fed obese rats.

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.

Attenuated baroreflex sensitivity in normotensive prediabetes and diabetes in Indian adults.

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.

Antihyperlipidemic and antioxidant activities of the ethanolic extract of Garcinia cambogia on high fat diet-fed rats.

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.

Curcumin prevents inflammatory response, oxidative stress and insulin resistance in high fructose fed male Wistar rats: Potential role of serine kinases.

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.

Curcumin Attenuates Oxidative Stress and Activation of Redox-Sensitive Kinases in High Fructose- and High-Fat-Fed Male Wistar Rats.

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.

Single nucleotide polymorphism of CYP3A5*3 contributes to clopidogrel resistance in coronary artery disease patients among Tamilian population.

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.

Can protein carbonyl/glutathione ratio be used as a potential biomarker to assess oxidative stress in alcoholic hepatitis?

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.

Increased glycation of hemoglobin in chronic renal failure: [corrected] potential role of oxidative stress.

Among the various mechanisms proposed, the process of non-enzymatic glycation of proteins is believed to play an important role in the pathogenesis of chronic complications associated with renal failure. The two traditional factors found to modulate the early glycation of proteins are the prevailing concentration of glucose and half life of the protein. Among the various proteins that are known to undergo nonenzymatic glycation in vivo, hemoglobin has been the most thoroughly investigated. Determination of glycated hemoglobin in diabetic patients is currently acknowledged as the most reliable indicator for assessment of retrospective glycemic control and the planning of clinical management. The clinical utility of glycated hemoglobin measurements, however, in renal failure is controversial, given the numerous earlier studies showing no correlation between glycated hemoglobin and other indicators of blood glucose control in uremic subjects. With few exceptions, previous studies have suggested that the concentration of glycated hemoglobin was increased in uremic patients. There is documented evidence that increased glycated hemoglobin levels are found in certain non-diabetic states. So it stands to reason that hyperglycemia, although clearly being the culprit in diabetes, does not provide the complete answer to the etiology of increased early glycated products in non-diabetic conditions including chronic renal failure. This article reviews available evidence supporting increased glycation of hemoglobin in patients with chronic renal failure. Potential mechanisms for this increase are examined with special emphasis on the potential role of oxidative stress.