The Relationship Between GAPDH Gene Polymorphism and Risk of Acute Coronary Syndrome in South Indians with Type 2 Diabetes Mellitus.

As glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is one of the regulators of carbonyl stress, a pathogenic mechanism for diabetic complications like acute coronary syndrome (ACS), the study aimed to investigate the relationship between GAPDH gene polymorphism, GAPDH activity in red blood cell (RBC), methylglyoxal (MG) levels in plasma and ACS risk in South Indians with type 2 diabetes mellitus (T2DM). This study comprised 150 T2DM with ACS as cases and 150 T2DM without ACS as controls. The GAPDH rs1136666, rs1060620 and rs1060619 gene polymorphisms were identified by TaqMan probe assays. The RBC GAPDH activity and plasma MG levels were estimated. Cases had significantly higher plasma MG levels and lower RBC GAPDH activity than controls (P < 0.001). The distribution of rs1060620 or rs1060619 alleles and genotypes significantly differed between groups. The rs1060620 AG (OR 0.55; 95% CI 0.33-0.92; P = 0.022) or rs1060619 CT (OR 0.51; 95% CI 0.31-0.83; P = 0.007) genotype was associated with reduced ACS risk, confirmed in the over-dominant genetic model. Haplotype analyses revealed that the GAT and CGC haplotypes were associated with increased (OR 28.37; 95% CI 3.82-210.49; P = 8.51 × 10-7) and decreased (OR 0.45; 95% CI 0.24-0.86; P = 0.014) ACS risk in T2DM patients, respectively. Lower GAPDH activity was observed in the TT and CT genotypes compared to the CC genotype of rs1060619 (P < 0.001). This work established that the GAPDH rs1060620 or rs1060619 gene polymorphisms are associated with ACS risk in South Indians with T2DM.

GC-MS validation and analysis of targeted plasma metabolites related to carbonyl stress in type 2 diabetes mellitus patients with and without acute coronary syndrome.

Methylglyoxal (MG) is responsible for advanced glycation end-product formation, the mechanisms leading to diabetes pathogenesis and complications like acute coronary syndrome (ACS). Sugar metabolites, amino acids and fatty acids are possible substrates for MG. The study aimed to measure plasma MG substrate levels using a validated gas chromatography-mass spectrometry (GC-MS) method and explore their association with ACS risk in type 2 diabetes mellitus (T2DM). The study included 150 T2DM patients with ACS as cases and 150 T2DM without ACS as controls for the analysis of glucose, fructose, ribulose, sorbitol, glycerol, pyruvate, lactate, glycine, serine, threonine, C16:0, C16:1, C18:0, C18:1, C18:2, C18:3, C20:0 and C22:6 by GC-MS. Validated GC-MS methods were accurate, precise and sensitive. Cases significantly differed in plasma MG and metabolite levels except for lactate, C16:0, C18:0, C18:2, and C18:3 levels compared with controls. On multivariable logistic regression, plasma C20:0, C18:1, glycine and glycerol levels had increased odds of ACS risk. On multivariate receiver operating characteristic analysis, a model containing plasma C20:0, C16:1, C18:1, C18:2, serine, glycerol, lactate and threonine levels had the highest area under the curve value (0.932) for ACS diagnosis. In conclusion, plasma C20:0, C16:1, C18:1, glycine, glycerol and sorbitol levels were associated with ACS risk in T2DM.

The Association of Sperm DNA Fragmentation With Serum Lipid Profile Among Males With Abnormal Semen Parameters: An Analytical Cross-Sectional Study.

BACKGROUND: Through the ages, infertility, affecting 8% to 12% of couples worldwide, has been a perturbing clinical problem. Approximately 40% to 50% of all infertility cases are due to 'male factor' infertility. Semen analysis is crucial in routinely evaluating idiopathic male infertility. Studies support the idea that semen parameters are associated with serum lipids and sperm DNA fragmentation (SDF). Therefore, it is possible to evaluate male infertility by serum lipid levels, especially before assisted reproduction technology, and modify it by bringing about lifestyle modifications. This study aimed to measure the correlation of SDF with levels of total cholesterol (TC), triglycerides (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) among males with abnormal semen parameters. METHODS: A cross-sectional analytical study was conducted in the infertility clinic of a tertiary care hospital. A total of 106 infertile males with abnormal semen analysis as per the WHO criteria (2010) were enrolled in the study. After routine semen analysis, SDF was studied using the comet assay. The serum fasting lipid profile was analyzed using the spectrophotometric kit in the autoanalyzer. The relationship of SDF with serum lipid profile parameters was analyzed. RESULTS: Out of 106 infertile men, 52% (n = 55) had severe SDF. A modest positive correlation was observed between SDF (percentage of DNA in comet tail) and serum lipid values (serum TG, serum LDL, and serum VLDL). CONCLUSIONS: Our study is novel in its research on the correlation between SDF and serum lipid values. Based on the findings of our study, it can be concluded that a significant level of SDF was observed in men with high levels of serum TG, LDL, and VLDL. This provokes a potential relationship between sperm DNA integrity and serum lipid profile, which warrants further research.

Cardiac Autonomic and Endothelial Function in Acute Lymphoblastic Leukaemia Patients Immediately After Chemotherapy and at the Three-Month Follow-up.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is a malignant uncontrolled overproduction of immature lymphoid cells in blood and bone marrow. The primary treatment of ALL is chemotherapy. Chemotherapy can have myriad systemic side effects, notably cardiovascular derangement. Autonomic derangement occurrence in cancer patients signifies cardiovascular risk in them and is a determinant of cardiovascular morbidity and mortality. Elevated soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) levels implicated in the regulation of inflammation indicate endothelial dysfunction. High levels of high-sensitivity C-reactive protein (hsCRP) can be indicative of low-grade inflammation. Hence, in this study the cardiac autonomic function and endothelial and inflammatory biomarker levels in adult patients with ALL were assessed immediately and three months after chemotherapy. METHODS: In this longitudinal study, 30 ALL patients (23 males, seven females) aged between 18 to 50 years, who had completed chemotherapy regimens, and 30 age and gender-matched healthy participants (controls) were recruited. Cardiac autonomic function tests (short-term heart rate variability (HRV), 30:15 ratio, synaptic excitation and inhibition (E/I) ratio, diastolic blood pressure (DBP) response to isometric hand grip), endothelial markers (sVCAM-1 and sICAM-1), and inflammatory marker (hsCRP) were assessed immediately and at three months after chemotherapy. RESULTS: Magnitudes of time domain and frequency domain indices, conventional autonomic function test indices, and biomarkers were deranged in ALL patients immediately after chemotherapy. After three months, cardiac autonomic function parameters were found to improve in the form of increased root mean square of successive differences between normal heartbeats (RMSSD), standard deviation of the interbeat intervals of normal sinus beats (SDNN), total power, high-frequency (HF)nu, and decreased low-frequency(LF)nu & LF-HF ratio. Endothelial (sVCAM-1) and inflammatory markers (hsCRP) were lower in the patient group as compared to the controls immediately after chemotherapy. Three months after chemotherapy, the levels of endothelial and inflammatory markers did not show much change. CONCLUSION: In this study, we found ALL patients showed higher sympathetic drive, decreased parasympathetic modulation, and sympathovagal imbalance immediately after chemotherapy as compared to the controls, indicating cardiovascular risk. After three months, improvement in cardiovascular autonomic function was observed. ALL itself is a state of inflammation with elevated endothelial and inflammatory markers; thus, the decreased endothelial and inflammatory markers could be attributed to the immediate effect of chemotherapy.

Urinary megalin levels in patients with type 2 diabetic nephropathy and its correlation with renal function.

Purpose: Megalin is a glycoprotein molecule found on proximal renal tubular epithelial cells. The objectives of this study were to determine urinary megalin levels in non-diabetic subjects and in patients with and without type 2 diabetic nephropathy and to assess the correlation between urinary megalin, urinary albumin, and estimated glomerular filtration rate (eGFR) in diabetic patients. Materials and Methods: This was a cross-sectional comparative study conducted at a tertiary care teaching hospital in South India for 2 years. Study subjects were divided into three groups: non-diabetic subjects, diabetics with normoalbuminuria, and diabetics with microalbuminuria. Urinary albumin was detected by the dipstick technique in a spot urine sample for all study subjects. Nephelometry was used to quantify urinary albumin levels. The enzyme-linked immunosorbent assay technique estimated urinary megalin. Results: Urinary megalin levels were higher in non-diabetic subjects compared to diabetic study subjects. There was a significant difference in urinary megalin levels between non-diabetic subjects and diabetic patients with microalbuminuria. No correlation was found between urinary megalin, urinary albumin, and eGFR in patients with diabetic nephropathy. Conclusion: Urinary megalin levels were higher in non-diabetic subjects than in type 2 diabetic patients. There was no correlation between urinary megalin, urinary albumin, and eGFR in patients with diabetic nephropathy.

Association of Tenascin-C Gene Polymorphisms with Risk of Acute Coronary Syndrome in South Indian Population: A Case-Control Genetic Association Study.

Background: The extracellular matrix (ECM) glycoprotein changes are associated with the pathogenesis and complications of atherosclerosis, leading to acute coronary syndrome (ACS). Tenascin-C (TNC), an ECM protein, has been implemented in the pathogenesis, diagnosis, and prognosis of patients with cardiovascular disease. Aim: The study aimed to compare the genetic variants of the TNC gene (rs13321, rs2104772, and rs12347433) between South Indians with ACS and healthy participants. Materials and Methods: This case-control study recruited 150 ACS patients as cases and 150 healthy participants as controls. TNC genotyping was performed using TaqMan 5'-exonuclease allele discrimination assay. Serum TNC levels were measured by enzyme-linked immunosorbent assay. Results: Serum TNC levels were significantly higher in cases compared with controls. No significant difference was observed in allele and genotype frequencies of rs13321, rs2104772, and rs12347433 between cases and controls, which was confirmed by dominant, recessive, codominant, and homozygotic genetic models. The patients with heterozygous genotypes of rs13321, rs2104772, and rs12347433 had significantly lower serum TNC levels than patients with respective homozygous genotypes. Haplotype analyses revealed that the C-T-A haplotype in the block of rs13321-rs12347433-rs2104772 was associated with lower ACS risk (OR = 0.33, 95% CI: 0.15 - 0.75; p = 0.005). Also, the C-T-T and G-T-A haplotypes of the TNC gene were associated with higher and lower serum TNC levels, respectively. Conclusion: Our study demonstrated no genetic association between single nucleotide polymorphisms of the TNC gene and ACS risk; however, the C-T-A haplotype of the TNC gene might be associated with reduced ACS risk in South Indians.

Deoxyribose Nucleic Acid Damage and Its Association With Plasma Malondialdehyde Levels Among Patients With Cervical Cancer: A Case-Control Study.

Purpose The objective of this research project was to estimate DNA damage in patients diagnosed with cervical cancer using the comet assay, establish a correlation between this quantification and the oxidative stress marker malondialdehyde (MDA; plasma MDA), and compare the resulting parameters between the cases and age-matched controls. Materials and methods This study included 49 cervical cancer cases and 49 age-matched controls to measure DNA damage parameters such as comet length, head diameter, percentage of DNA in the comet head, tail length, percentage of DNA in the comet tail, and oxidative stress marker (plasma MDA) using the thiobarbituric acid reactive substance (TBARS) enzyme-linked immunosorbent assay (ELISA) method. Results Comet metrics suggesting DNA damage, such as comet length, tail length, and percentage of DNA in the comet tail, were considerably higher in cervical cancer cases than in age-matched controls. The proportion of DNA in the comet head, representing undamaged/mild DNA damage, was significantly higher in age-matched controls than in cervical cancer patients. Plasma MDA and comet tail length were shown to have a positive correlation. Compared to the age-matched controls, those between the ages of 30 and 39, with a parity of two to four, who had a history of early age at first pregnancy and a positive family history of cervical cancer, had the highest level of DNA damage. Conclusion The elevated levels of comet parameters and their positive correlation with plasma MDA suggest that individuals diagnosed with cervical cancer have a higher degree of DNA damage compared to the control group. In conjunction with established methods like the PAP smear, this predictive test comprising comet assay and estimation of plasma MDA may be utilized to identify and assess the risk of cervical cancer in individuals aged 30-39 years, with a parity between two and four pregnancies and a prior history of early age at first pregnancy, accompanied by a positive family history of the disease.

The genetic polymorphisms and activity of glyoxalase 1 as a risk factor for acute coronary syndrome in South Indians with type 2 diabetes mellitus.

OBJECTIVE: The individuals' genetic traits predispose them to a higher or lower risk of Type 2 diabetes mellitus (T2DM) and its complications, for example, acute coronary syndrome (ACS). As carbonyl stress is responsible for the pathogenesis and complications of T2DM, and glyoxalase 1 (GLO1) is the most crucial determinant of carbonyl stress, the study aimed to explore the association between GLO1 gene polymorphism, GLO1 activity in red blood cell (RBC), plasma methylglyoxal (MG) levels, and ACS risk in South Indian T2DM patients. METHODS: A total of 150 T2DM patients with ACS as cases and 150 T2DM patients without ACS as controls were recruited in a case-control study. The rs4746, rs1049346 and rs1130534 of the GLO1 gene were analysed using TaqMan allele discrimination assay. The RBC GLO1 activity and plasma MG levels were measured. RESULTS: Significantly lower RBC GLO1 activity and higher plasma MG levels were found in cases compared to controls (p < 0.001 and p = 0.008, respectively). The genotype and allele frequencies of rs1049346 significantly differed between cases and controls (p < 0.001). For rs1130534 and rs1049346, no significant difference was found. For rs1049346, the TT and CC genotypes were associated with higher (p = 0.002) and lower (p = 0.001) ACS risk, respectively, in various genetic models. The TT genotype of rs1049346 was associated with lower RBC GLO1 activity (p = 0.004) and higher MG level (p = 0.010). In haplotype analysis, higher ACS susceptibility with the TAT haplotype (p < 0.001) and lower ACS susceptibility with the TAC haplotype (p < 0.001) were observed. Also, lower RBC GLO1 activity was associated with the TAT haplotype (p = 0.002). CONCLUSIONS: The rs1049346 of the GLO1 gene may be associated with ACS risk in South Indian T2DM patients, and the T and C allele might be essential precipitating and protective factors, respectively.

Body Iron Store and its Association with Risk of First Episode of Spontaneous Lower Extremity Deep Vein Thrombosis/ Pulmonary Embolism: A Case-Control Study.

Background and objectives: The association between body iron stores and risk of deep vein thrombosis/ pulmonary embolism (DVT/ PE) has not been studied among Indian subjects. This study aimed to evaluate the same and also study the association between iron stores and recanalization of affected veins at week-12. Methods: This Case-Control with follow-up study enrolled 85 consecutive adult (≥ 18 years) cases presenting with first episode of spontaneous, proximal lower extremity DVT/ PE and 170 age (± 3 years) and sex matched adult controls without DVT/ PE. Those with haemoglobin(Hb) < 9 g/dl, malignancies, serum creatinine ≥ 2 mg/dL, heart failure and concurrent infections/ inflammatory disorders were excluded. All participants underwent iron profile, serum ferritin light-chain (FtL) and hepcidin testing. Results: Anaemia [OR = 2.3 (95% CI = 1.3-4.0), p = 0.001] and elevated RDW (RDW-CV > 15%) [OR = 2.3 (95% CI = 1.2-4.3), p = 0.012] were significantly associated with increased risk of DVT/ PE. Iron deficiency (ID, defined as serum ferritin < 30 µg/L, along with TSAT < 20%) was not associated with DVT/ PE risk [OR = 0.8 (95% CI = 0.4-1.7), p > 0.05]. Serum FtL in the highest quartile (> 75th centile) was associated with higher risk of DVT/ PE (OR = 5, 95% CI = 2.6-9.6) and levels < 25th centile with protection against DVT/ PE (OR = 0.1, 95% CI = 0.01-0.32), compared to levels between 25th and 75th centiles (referent range). Highest DVT/ PE risk was associated with FtL > 90th centile [OR≈12 (95% CI = 3.9-37.2)]. No associations were noted between serum hepcidin and DVT/ PE risk and ID and DVT recanalization at week-12. Conclusion: Higher iron stores, rather than ID, were associated with increased risk of DVT/ PE among those with Hb ≥ 9 g/dL. Anaemia and elevated RDW were also associated with risk of DVT/ PE. ID was not associated with poorer DVT recanalization at week-12.

A validated and optimized method for separation and quantification of total fatty acids by gas chromatography-ion trap mass spectrometry in human plasma.

Fatty acids (FAs) are associated with many physiological functions of tissues, and their alteration has been linked with tissue-specific or systemic diseases. The current situation warrants us to have a sensitive and specific method for analysis of total FAs simultaneously from the biological fluid so that the risk prediction, diagnosis or prognosis of the disease can be made effectively. Because of greater sensitivity and resolution, a method of gas chromatography-ion trap mass spectrometry (GC-IT/MS) has been optimized and validated to quantify simultaneously 19 total FAs levels in plasma and compared with GC-triple quadrupole mass spectrometry. FAs have been transesterified by methanolic acetyl chloride to fatty acid methyl esters (FAMEs). A 65 min GC method separated all 19 FAMEs. The calibration curve had good linearity up to 313-922 µM with a correlation coefficient between 0.9882 and 0.9998. The LODs and LOQs of FAMEs were in the range of 0.63 to 9.55 and 2.12 to 31.8 µM, respectively. The method has recovery up to 144 %, stability at 4 °C for 48 h and one freeze-thaw cycle, and good intra-day and inter-day precision. The optimized method has been used to quantify plasma total FAs in type 2 diabetes mellitus patients with and without acute coronary syndrome. Though a significant difference has been found between IT/MS and triple quadrupole mass spectrometry, the GC-IT/MS can help to quantify total FAs in the clinical setting.

Altered expression of a disintegrin and metalloproteinase 10 in peripheral blood mononuclear cells in type 2 diabetes mellitus patients with the acute coronary syndrome: a pilot study.

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: Reduced expression of ADAM10 in PBMC might be responsible for lower serum sRAGE levels, predisposing T2DM patients to high ACS risk.

Presepsin vs Procalcitonin as Predictors of Sepsis Outcome.

BACKGROUND: Sepsis diagnosis and management is aided by the use of newer biomarkers like procalcitonin and presepsin. For prognostication, presepsin may be better than procalcitonin. METHODOLOGY: Ninety-two participants, suspected to be suffering from sepsis of varied etiologies were included in this study at the time of their presentation to the emergency health services. Presepsin and procalcitonin were estimated and the patient followed up till discharge or death. Receiver operating curve (ROC) curves, sensitivity, specificity, and positive and negative likelihood ratios were calculated. Association between these markers and mortality was estimated. RESULTS: Out of 92 participants enrolled on day 1, 73 survived till day 3. Patients who had thrombocytopenia, high neutrophil counts, and elevated levels of bilirubin, urea, presepsin, and procalcitonin were associated with poor outcomes. Presepsin and procalcitonin levels increased significantly from day 0 to day 3 in the nonsurvivor group as compared to the survivor group. On comparing the ROC curve of presepsin and procalcitonin, the area under the curve (AUC) of presepsin was more than procalcitonin, signifying that it was a better biomarker of mortality due to sepsis. At a cutoff value of 1.47 ng/dL, presepsin was a predictor of mortality in sepsis [odds ratio (OR) = 14]. It had similar sensitivity but better specificity than procalcitonin in predicting mortality.

Association between serum netrin-1, netrin-4 and risk of the acute coronary syndrome in patients with type 2 diabetes mellitus-A pilot study.

The present study was done to assess the diagnostic utility of serum netrin-1 and netrin-4 for recognising the acute coronary syndrome (ACS) in type 2 diabetes mellitus (T2DM) patients. Forty-two T2DM patients with ACS (Cases) and forty-two T2DM patients without ACS (Controls) were compared. Cases had lower serum netrin-1 and netrin-4 levels than controls and were negatively associated with creatinine kinase-total, creatinine kinase-MB, troponin-T and H-FABP. ROC analysis showed that netrin-1 and netrin-4 had good sensitivity and specificity for ACS prediction in T2DM patients. Serum netrin-1 and netrin-4 levels might be considered complementary markers for ACS diagnosis in T2DM patients.

Procalcitonin Assay Has No Role in the Routine Assessment of Severe Trauma Patients at Admission to the Emergency Department.

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 <8, head and neck injuries, and extremity injuries were found to be significantly associated with mortality. Bloodstream infections were more common in the presence of lung contusions, abdominal injury, operative management, and blood transfusions. PCT levels at admission did not have a significant predictive value for mortality, bloodstream infections, other infectious complications, or length of ICU stay. Conclusions Head injuries were the most common cause of mortality in our study. In addition to the anatomical region involved, ISS and GCS have a significant association with mortality. PCT levels at ED admission do not have any prognostic value and need not be routinely analysed.

Carbonyl stress in diabetics with acute coronary syndrome.

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.

Association of serum calprotectin with peripheral neuropathy in patients with type 2 diabetes mellitus.

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.

Assessment of Organophosphate Pesticides Exposure in Men with Idiopathic Abnormal Semen Analysis: A Cross-Sectional Pilot Study.

BACKGROUND: Because of the widespread use of organophosphate (OP) pesticides in agriculture, they are major environmental contaminants in developing countries. OP pesticides decrease sperm concentration and affect its quality, viability, and motility. studies have demonstrated the association between abnormal semen analysis and OP pesticides exposure among the high-risk population. Asthere is limited data on the percentage of OP pesticides exposure, the study aimed to determine the OP pesticides exposure in Southern Indian men with idiopathic abnormal semen analysis and find the possible source of their OP pesticides exposure. MATERIALS AND METHODS: In this cross-sectional pilot study, fifty men with idiopathic abnormal semen analysis as cases and fifty men with normal semen analysis as controls were recruited. Detailed history wastaken and general and systemic examinations were carried out. OP pesticides exposure was determined by assessment of pseudocholinesterase and acetylcholinesterase levels and urinary OP pesticides metabolites dialkyl phosphate (DAP) consisting of dimethyl phosphate (DMP), diethyl thiophosphate (DETP), and diethyl dithiophosphate (DEDTP). RESULTS: Cases had statistically significantly lower levels of pseudocholinesterase (5792.07 ± 1969.89 vs. 10267.01 ± 3258.58 IU/L) (P=0.006) and acetylcholinesterase [102.90 (45.88-262.74) vs. 570.31 (200.24-975.30) IU/L] (P=0.001) as compared to controls. Cases had a statistically significantly higher percentage of urinary DAP positivity as compared to controls (80 vs. 38%, P<0.0001). Hence, cases had a significantly higher percentage of OP pesticides exposure as compared to controls (20 vs. 4 %, P=0.015). OP-exposed cases had significantly higher urinary DETP and DEDTP levels as compared to OP non-exposed cases. Also, urinary DETP and DEDTP levels were significantly negatively associated with sperm concentration, motility, and normal morphology among OP-exposed cases. CONCLUSION: Southern Indian men with idiopathic abnormal semen analysis had a significantly higher percentage of OP pesticides exposure as compared to men with a normal semen analysis.

Clinical utility of validated gas chromatography-ion trap mass spectrometry in patients with anticholinesterase pesticides poisoning.

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.

Assessment of serum tenascin-C and growth differentiation factor-15 among type 2 diabetes mellitus patients with and without acute coronary syndrome.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: T2DM patients with higher serum GDF-15 and TNC levels were at higher risk of acute coronary syndrome independent of other cardiovascular risk factors.

Cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus and its association with serum omentin and leptin.

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.