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Advanced glycation end products (AGEs) are responsible for the complications in type 2 diabetes mellitus (T2DM) patients by acting via its receptor (RAGE). The soluble form of RAGE (sRAGE) prevents the harmful effects of AGE-RAGE signalling. The sRAGE is produced either by alternate splicing (esRAGE) or proteolytic RAGE cleavage by a disintegrin and metalloproteinase 10 (ADAM10). Hence, the study aimed to compare the expression of ADAM10 in peripheral blood mononuclear cell (PBMC), serum sRAGE and esRAGE levels in T2DM patients with and without acute coronary syndrome (ACS).Forty-five T2DM patients with ACS and 45 age, gender and duration of DM-matched T2DM patients without ACS were recruited. Serum sRAGE and esRAGE levels were measured by enzyme-linked immunosorbent assay. The expression of ADAM10 in PBMC was determined by quantitative reverse transcription-polymerase chain reaction.The expression of ADAM10 in PBMC and serum sRAGE levels were significantly lower in T2DM patients with ACS than in T2DM patients without ACS (p 0.001). Serum sRAGE levels and expression of ADAM10 in PBMC were positively correlated with each other and negatively correlated with markers of cardiac injury and glycaemic status (p 0.05). Simple logistic regression showed that the models containing the expression of ADAM10 and serum sRAGE level could predict the ACS risk among T2DM patients. ROC analysis showed that both might be used for ACS diagnosis in T2DM patients.Reduced expression of ADAM10 in PBMC might be responsible for lower serum sRAGE levels, predisposing T2DM patients to high ACS risk.

The prevalence and incidence of diabetes mellitus (DM) are increasing worldwide bringing with it a significantly higher rate of complications. Various mechanisms such as carbonyl stress, polyol pathway, oxidative stress, hexosamine pathways, diacylglycerol/protein kinase-C activation, etc., are responsible for the pathogenesis of DM and its complications. Persistent hyperglycaemia and inhibition of metabolising and detoxifying enzymes lead to the excessive synthesis of carbonyl compounds such as methylglyoxal, glyoxal, and 3-deoxyglucosone, resulting in carbonyl stress. The substrates, metabolizing and detoxifying enzymes of carbonyl compounds are discussed. The mechanistic roles of carbonyl compounds and advanced glycation end products (AGEs) in atherosclerosis, insulin resistance, thrombogenicity, and endothelial dysfunction in animal and cell culture model of DM and patients with DM are summarised. Because of the essential role of carbonyl stress, therapeutics are aimed at scavenging, metabolizing, detoxifying, and inhibiting carbonyl compounds or AGEs so that their harmful effects are minimized. Clinically used drugs, plants extracts and miscellaneous chemical with antiglycation properties are used in an animal model of DM to alleviates the impact of carbonyl compounds. Extensive clinical trials with derivatisation of available antiglycation agents to increase the bioavailability and decrease side effects are warranted further.

High prevalence of type 2 diabetes mellitus (T2DM) is associated with a higher prevalence of acute coronary syndrome (ACS). Inflammation is one of the important contributors to the pathogenesis and complications of coronary atherosclerotic plaque. Growth Differentiation Factor-15 (GDF-15) and Tenascin-C (TNC) play an important role in the initiation of atherosclerotic plaque as well as its rupture. The aim of the study was to evaluate the association between serum GDF-15, TNC, and the risk of ACS among T2DM patients.Anthropometric parameters, routine biochemical investigations like liver and renal function tests, lipid profile, and Creatine Kinase-Total (CK-T), Creatine Kinase-MB (CK-MB) were measured in 42 T2DM patients with ACS and 42 T2DM patients. Serum GDF-15 and TNC were measured by Human Sandwich-ELISA kits.Serum GDF-15 and TNC levels were significantly higher in T2DM patients with ACS as compared to T2DM patients. Serum GDF-15 was significantly correlated with waist circumference, diastolic blood pressure, pulse, serum CK-T, and CK-MB. Serum TNC was significantly correlated with the pulse, serum CK-T, CK-MB, high-density lipoprotein-cholesterol, and blood urea nitro GEN. Multivariate linear regression analysis showed that waist circumference was independently positively associated with serum GDF-15.T2DM patients with higher serum GDF-15 and TNC levels were at higher risk of acute coronary syndrome independent of other cardiovascular risk factors.Visoka prevalenca dijabetes melitusa tipa 2 (T2DM) povezana je sa većom prevalencom akutnog koronarnog sindroma (ACS). Upala je jedna od važnih stavki u patogenezi i komplikacijama koronarnog aterosklerotskog plaka. Faktor diferencijacije rasta-15 (GDF-15) i tenascin-C (TNC) igraju važnu ulogu u pokretanju aterosklerotskog plaka, ali i njegovom pucanju. Cilj studije bio je da se proceni povezanost između seruma GDF-15, TNC-a i rizika od ACS-a kod pacijenata sa T2DM.Kod 42 pacijenta koji boluju od T2DM sa ACS i 42 pacijenta sa T2DM izmereni su antropometrijski parametri, rutinska biohemijska ispitivanja poput testova jetre i funkcije, lipidni profil i ukupna kreatin kinaza (CK-T), kreatin kinaza-MB (CK-MB). Serum GDF-15 i TNC su mereni pomoću humanih sendvič-ELISA kitova.Serumski nivo GDF-15 i TNC su bili značajno viši kod T2DM pacijenata sa ACS u poređenju sa T2DM pacijentima. Serumski GDF-15 je bio značajno povezan sa obimom struka, dijastolnim krvnim pritiskom, pulsom, serumskim CK-T i CK-MB. TNC u serumu je bio značajno povezan sa pulsom, serumskim CK-T, CK-MB, lipoprotein holesterolom visoke gustine i azotom uree u krvi. Multivarijantna linearna regresiona analiza pokazala je da je obim struka nezavisno pozitivno povezan sa serumskim GDF-15.Pacijenti sa T2DM sa većem nivoom GDF-15 i TNC u serumu su bili izloženi većem riziku od akutnog koronarnog sindroma nezavisno od ostalih kardiovaskularnih faktora rizika.

Introduction A key challenge in emergency departments (ED) is the early recognition of sepsis or the potential for sepsis in patients. Appropriate and accurate ED triage will ensure improved case management. This study analysed the association between ED findings at admission and outcomes in patients presenting with severe trauma. Methods This was a prospective study conducted at a tertiary level ED and included severely injured adult patients who presented to the ED within 24 hours of injury. Data collected included clinical findings and imaging reports at initial assessment, serum procalcitonin (PCT), length of ICU and hospital stay, the incidence of bloodstream and other infections, and patient outcome as discharge from care or death. Multiple logistic regression was used to assess the association between outcome variables and independent variables. Results A total of 155 patients were included in the study. Head and neck (61.9%), extremity (58%), and chest (45%) were more commonly injured. Injury Severity Score (ISS) >25, Glasgow Coma Scale (GCS) score

Intentional or unintentional intake of anticholinesterase pesticides became common due to their extensive use in agricultural and domestic purposes, resulting in numerous poisoning cases. A simple, accurate, and sensitive gas chromatography-ion trap mass spectrometry-based method for the quantification of 12 anticholinesterase pesticides (monocrotophos, dimethoate, dichlorvos, azinphos-methyl, carbofuran, chlorpyrifos, dialifos, diazinon, malathion, parathion, methidathion, and terbufos) in serum was developed, and its utility in patients with alleged pesticides poisoning was assessed. The quantification was performed using liquid-liquid extraction by toluene/chloroform (4:1,v/v) with 500 μL of serum. On column limit of detection and limit of quantification were less than 50.00 μg/L. The recovery ranged from 97.54 to 103.23%. The calibration curves were linear (R2 > 0.9937). Accuracy was found to be between – 7.1 and 7.2%. Intra-day and inter-day reproducibility was less than 17% for the spiked quality control serum samples. The level of pesticide in serum quantified by the validated method correlated with clinical signs and symptoms, pseudo-cholinesterase activity, total atropine dose, length of hospital stay, and clinical outcome in 15 patients with alleged pesticide poisoning. The validated method may be used for monitoring and prognosis in patients with pesticide poisoning and diagnosis of poisoning in forensic toxicology.

Background and aims Carbonyl stress is one of the mechanisms responsible for diabetes and its complications. The study was planned to examine the relationship between carbonyl stress markers and the risk of acute coronary syndrome (ACS) in patients with type 2 diabetes mellitus (T2DM). Methods Forty T2DM patients with ACS and forty T2DM patients without ACS participated in this cross-sectional pilot study. Routine biochemical investigations, creatine kinase-total (CK-T), and creatine kinase-MB (CK-MB) levels were estimated. Serum carbonyl stress markers were analysed by enzyme-linked immunosorbent assay. Binary logistics regression was done to determine the predictive value of carbonyl stress markers for ACS. Results Fasting plasma glucose, serum total methylglyoxal (MG), methylglyoxal derived hydroimidazolones-1 (MG-H1), and Ne-carboxymethyl-lysine (CML) levels were significantly higher in T2DM patients with ACS than in those without ACS. Serum glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glyoxalase-1 (GLO1) levels were significantly lower in T2DM patients with ACS than in those without ACS. Fasting plasma glucose level was significantly positively correlated with serum MG (r = 0.441, P Conclusion These findings revealed that high carbonyl stress due to lower levels of GAPDH and GLO1 may predispose patients with T2DM for more risk of ACS.

Background and aims Regenerating islet-derived protein 3-beta (Reg3β) and oncostatin-M (OSM), an inducer of Reg3β, are important for the recruitment of macrophages, tissue repair and survival after myocardial infarction. The study was planned to elucidate the diagnostic utility of serum Reg3β and OSM levels for the acute coronary syndrome (ACS). Methods Forty-two type 2 diabetes mellitus (T2DM) patients with ACS as cases and forty-two T2DM patients as controls were recruited. Routine biochemical investigations, creatine kinase-total (CK-T), and creatine kinase-MB (CK-MB) levels were estimated. Serum Reg3β and OSM levels were analysed by enzyme-linked immunosorbent assay. Results Serum Reg3β and OSM levels were significantly higher in cases as compared to controls. Serum Reg3β and OSM levels were positively correlated with random blood glucose, serum CK-total, CK-MB levels, and negatively correlated with serum high-density lipoprotein cholesterol (HDL-C) levels. Receiver operating characteristics curve analysis showed that serum OSM and Reg3β levels can be used for the diagnosis of ACS in patients with T2DM as compared to CK-MB levels. On regression analysis, serum Reg3β level was positively associated with body mass index and negatively with serum HDL-C levels and serum OSM level was positively associated with waist circumference and random blood glucose and negatively with serum HDL-C levels. Conclusion Serum Reg3β and OSM levels may be used as complementary markers besides traditional cardiac markers for the diagnosis of ACS in patients with T2DM. However, further studies are still needed to verify our claim.

Background Patients with Bipolar Disorder (BD) may have higher risk of Tardive Dyskinesia (TD). Theories for TD include inflammatory or oxidative stress and altered iron metabolism. The current frequency and clinical and biochemical correlates of TD in BD needs exploration. Objectives To assess: (1) the frequency of TD in BD; (2) clinical correlates of TD in BD; (3) oxidative stress markers, inflammatory markers and hepcidin in TD in BD. Materials & methods In this cross-sectional study, 170 patients with BD were assessed for clinical characteristics using structured assessments. Inflammatory and oxidative markers like Interleukin-6 (IL-6), high sensitivity C-Reactive Protein (hsCRP), malondialdehyde (MDA), Total Antioxidant Status (TAS) and hepcidin were assessed by ELISA. Results Frequency of TD was 10.6% (95%C.I. = 6.4%–16.2%). Compared to patients without TD, patients with TD were older (F = 0.340;p = 0.000), had more episodes of illness (U = 962.5;p = 0.044) higher rates of medical comorbidity ( X 2 = 6.924; p = 0.009*), antipsychotic exposure (U = 592.5;p = 0.000), typical antipsychotic exposure (U = 756.5;p = 0.001) and cognitive deficits (F = 1.129;p = 0.001). The biomarkers levels did not differ between the groups. Hepcidin levels correlated with Abnormal involuntary Movements scale (AIMS) score (r = 0.213;p = 0.006). Patients treated with lithium were more likely to have TD, but also had greater exposure to antipsychotics than patients on valproate. Conclusion About one-tenth of patients with BD-I have TD. The presence of TD is associated several clinical characteristics such as age, exposure to typical antipsychotics and chronicity of illness. Hepcidin was associated with greater severity of dyskinetic movements and needs further exploration.

Introduction Early achievement of therapeutic INR leads to shorter hospital stay and lesser cost. Two warfarin initiation nomograms (10 mg nomogram and 5 mg nomogram) are widely used but it is not yet clear which one is better. They have been validated in the West but there are no studies from India. We undertook this study to compare the efficacy and safety of the 10 mg and 5 mg nomograms in the Indian population. Methods 169 patients were enrolled between august 2014 to July 2016. Patients with venous thromboembolism or atrial fibrillation secondary to valvular heart disease were included. Patients were allocated to 10 mg or 5 mg nomogram as per the policy of the treating unit. Results 52% of patients in the 10 mg nomogram achieved therapeutic INR by day 5 as compared to only 17% in the 5 mg nomogram (P = 0.022). The median time to achieve therapeutic INR was much shorter in the 10 mg nomogram (5 days vs 14 days, p = 0.018). Two patients in the 10 mg group (2.3%) and none in the 5 mg group had INR > 4 but they did not have any bleeding. Conclusion The 10 mg nomogram achieved therapeutic INR significantly earlier with less INR measurements and appears safe. Indian patients require higher a dose of warfarin at initiation and maintenance as compared to other ethnic groups.

In the search for the ideal intravenous induction drug, etomidate is in the forefront as it provides haemodynamic stability without compromising on the end point of induction. It has been established that slowing the rate of infusion of propofol decreases the dose required for induction. Even though etomidate provides good haemodynamic stability while inducing, there is concern about its cortisol suppressive function. This study has been designed, with entropy guidance, to establish whether induction by slowing the rate of infusion of etomidate will reduce the dose required for induction and simultaneously assess whether adverse effects are reduced. Ninety-six patients were randomly allocated into three groups based on etomidate dose. Etomidate dose was given till both loss of eyelash reflex and entropy50 was achieved. Total dose of etomidate consumed, time taken for loss of eye lash reflex and time to reach entropy50 were recorded. Cortisol levels were measured at different intervals. We observed that slowing the rate of infusion reduced the dose of etomidate for induction; however, it prolonged the time for induction of anaesthesia. Cortisol levels were suppressed in the first 6 h after induction in all three groups, but remained within normal limits and reached to pre induction levels by 24 h. The slower the rate of infusion, the lesser the dose of etomidate used for induction, but prolongs the time taken to reach the end point of induction. Incidence of myoclonus might be avoided by infusing etomidate for induction at a lower rate. Clinical Trials Registry of India, CTRI/2016/04/006879, www.ctri.nic.in/

Introduction: Peripheral neuropathy is a common microvascular complication in patients with type 2 diabetes mellitus with a prevalence of around 50%. Objectives: This prospective observational cross-sectional study was done to assess serum calprotectin levels among diabetic patients with peripheral neuropathy as compared to those without neuropathy. Methods: This cross-sectional study was conducted in 126 diabetic patients attending the out-patient department of JIPMER Hospital, Pondicherry from July 2017 to January 2019. The subjects were divided into two groups (with and without peripheral neuropathy) and underwent nerve conduction study of both the lower limbs. Blood samples were collected and stored at −80°C for estimation of serum calprotectin. Serum calprotectin levels were compared between diabetic patients with and without peripheral neuropathy. Results: Serum calprotectin levels were increased in patients with diabetic peripheral neuropathy (DPN) as compared to those without DPN. However, there was no significant difference in the mean value of serum calprotectin among the various sub-groups of DPN. Conclusion: Serum calprotectin, an inflammatory biomarker is elevated in patients with diabetic peripheral neuropathy as compared to those without neuropathy.

Cardiovascular autonomic neuropathy (CAN) is a major cause of morbidity and mortality in patients with diabetes as it is associated with a high risk of cardiac arrhythmias. Objectives: This prospective observational cross-sectional study was done to estimate the prevalence of CAN in patients with type 2 diabetes and to study its association with serum omentin and leptin levels. Methods: This study included 100 patients with type 2 diabetes mellitus attending the outpatient department of JIPMER Hospital, Pondicherry, India, from January 2017 to December 2018. CAN was assessed in all subjects using four cardiovascular autonomic function tests. Blood samples were collected and stored at - 80°C to estimate leptin and omentin levels. Comparison of leptin and omentin levels was done between diabetic patients with and without CAN. Results: CAN was present in 64% of the study subjects. Serum leptin levels were significantly higher in patients with CAN, whereas omentin levels, though elevated in those with CAN, were not statistically significant in diabetic patients without CAN. Conclusion: There is a high prevalence of CAN in patients with type 2 diabetes mellitus. Leptin levels were elevated in these patients, whereas omentin levels were not significantly different between diabetic patients with and without CAN.

Determination of time since death is one of the important objectives of a medicolegal autopsy. The level of electrolytes present in the body fluids acts as a helpful indicator in this regard. Nowadays cold chambers are present in most of the autopsy centres where the body is stored for a variable period of time at a temperature which is different from the environmental temperature. This study was undertaken to know the effect of the cold chamber temperature on the changes in sodium, potassium and chloride levels of vitreous humor and plasma and also to estimate the time since death from the levels of these electrolytes. For this, the study subjects were exposed to the cold chamber temperature (in a range of +2 °C to +4 °C) for a variable duration of time before beginning the autopsy. The results obtained substantiate the fact that the temperature of the cold chamber has a significant effect on the change in vitreous humor potassium level. In subjects exposed to the cold chamber, there was a statistically significant negative correlation between the sodium and chloride levels of vitreous humor with time since death. The R-squared value for the regression equation to predict time since death from vitreous humor sodium level was found to be 0.0916 and was considered a significant predictor of time since death.

Background & objectives: Simultaneous administration of phenytoin and isoniazid (INH) in tuberculous meningitis (TBM) or tuberculoma patients with seizures results in higher plasma phenytoin level and thus phenytoin intoxication. N-acetyltransferase 2 (NAT2) enzyme catalyses two acetylation reactions in INH metabolism and NAT2 gene polymorphism leads to slow and rapid acetylators. The present study was aimed to evaluate the effect of allelic variants of N-acetyltransferase 2 (NAT2) gene as a predisposing factor for phenytoin toxicity in patients with TBM or tuberculoma having seizures, and taking INH and phenytoin simultaneously. Methods: Sixty patients with TBM or tuberculoma with seizures and taking INH and phenytoin simultaneously for a minimum period of seven days were included in study. Plasma phenytoin was measured by high performance liquid chromatography. NAT2 gene polymorphism was studied using restriction fragment length polymorphism and allele specific PCR. Results: The patients were grouped into those having phenytoin intoxication and those with normal phenytoin level, and also classified as rapid or slow acetylators by NAT2 genotyping. Genotypic analysis showed that of the seven SNPs (single nucleotide polymorphisms) of NAT2 gene studied, six mutations were found to be associated with phenytoin intoxication. For rs1041983 (C282T), rs1799929 (C481T), rs1799931 (G857A), rs1799930 (G590A), rs1208 (A803G) and rs1801280 (T341C) allelic variants, the proportion of homozygous mutant was higher in phenytoin intoxicated group than in phenytoin non-intoxicated group. Interpretation & conclusions: Homozygous mutant allele of NAT2 gene at 481site may act as a predisposing factor for phenytoin intoxication among TBM or tuberculoma patients having seizures.

Background: One of the most predominant macrovascular complications of type 2 diabetes mellitus (T2DM) is acute coronary syndrome (ACS). Advanced glycation end products (AGEs) play an important role in the development and progression of ACS in T2DM patients. The soluble receptor of AGEs (sRAGE) decoys the effect of AGEs by binding with them. Objectives: The objectives of the study were to measure serum ɛN-carboxymethyllysine (CML) and sRAGE levels among T2DM with and without ACS and to find out whether serum CML and sRAGE could be used to predict the risk of ACS among T2DM patients. Materials and Methods: A total of 37 T2DM patients with ACS were selected as cases and 37 T2DM as controls. Routine biochemical parameters were carried out on autoanalyzer and serum CML and sRAGE were estimated by ELISA. The data were recorded and analyzed on SPSS system and were compared by Student’s t-test or Mann–Whitney test. Results: Serum CML level and CML/sRAGE ratio were significantly increased in the cases as compared to control. Correlation analyses showed that serum CML concentration and serum CML/sRAGE ratio were positively correlated with weight, waist circumference, body mass index and serum urea, and very low-density lipoprotein-cholesterol. Multivariate regression (Binary logistics) analysis after adjusted for waist circumference, weight, BMI, and systolic blood pressure showed that serum CML was significantly associated with ACS risk among T2DM patients. Receiver operating characteristic curve depicted that high CML level (>31.83 ng/ml) and CML/sRAGE ratio (>15.48) were associated with greatest risk of ACS among type 2 DM patients. Conclusion: T2DM patients with high serum CML concentration and CML/sRAGE ratio were at risk of ACS independent of other cardiovascular risks.