Sandeep Bhattacharya

Association of Genetic Polymorphism of GSTT1, GSTM1 and GSTM3 in COPD Patients in a North Indian Population

Environmental exposures and genetic susceptibility can contribute to lung function decline in chronic obstructive pulmonary disease (COPD). Cigarette smoking is the main etiological factor for decline in lung function in COPD. However, only 10–20% chronic smokers develop symptomatic COPD. Genetic susceptibility to COPD might depend upon the variation of enzyme activities that detoxify cigarette smoke components. We performed a case control study to assess the association of Glutathione- S-transferase T1(GSTT1),Glutathione- S-transferase M1 (GSTM1), and Glutathione-S-transferase M3(GSTM3) common polymorphisms with the susceptibility to COPD patient in a north India population. In the present study, the genotypes of 412 subjects, (204 COPD patients and 208 healthy controls) were analyzed. Statistical analysis revealed that the frequency of homozygous GSTM1 null genotype was found to be significant higher in COPD patients as compared with healthy controls (OR, 2.58; 95% CI, 1.73–3.84; P = 0.001), but there were no significant differences in the distribution of homozygous null GSTT1 and 3-bp deletion polymorphism (rs1799735) in intron 6 variant allele in GSTM3 between COPD patients and healthy controls. Our study results suggest that GSTM1 null polymorphism is associated with genetic susceptibility to COPD. Moreover, we also found association between this polymorphism with pulmonary function test in smokers as well as nonsmokers.

Association of Cytokine Gene Polymorphisms in Patients with Chronic Obstructive Pulmonary Disease

OBJECTIVE Chronic obstructive pulmonary disease (COPD) is a major health problem. The disease is driven by abnormal inflammatory reactions in response to inhaled particles and fumes. Therefore, inflammatory mediators are postulated to be of distinct importance. Keeping in view of the above facts; we investigate the role of polymorphisms of cytokine genes in the genetic predisposition of COPD. METHODS In this present case-control study, the allele and genotype distributions of IL1B, IL1RN, TNF-α, and IL4 were studied in COPD patients (N=204) and healthy individuals (N=208). Genomic DNA was obtained by whole blood and genotyping was carried out by a polymerase chain reaction (PCR) based Restriction Fragment Length Polymorphism technique. RESULTS Genotype IL1RN*2/IL1RN*2 was identified as protective for male COPD, its frequency being 8.7% in COPD patients and 14.6% in healthy subjects (p=0.017; OR=0.53), but IL1RN*1/IL1RN*2 turned out to be a risk factor for females COPD. No significant differences were found between the groups of COPD patients and healthy subjects concerning the genotype frequencies of the polymorphisms T (-511) C of IL1B and 70bp VNTR of IL-4. Genotype GA of the TNF-α polymorphism G (-308) A was more common in the COPD patients than in the controls (20.5% vs.14.4%; p=0.107), and allele A was significantly associated with COPD patients (p=0.023; OR=0.65). CONCLUSION IL-1RN *2 allele appears to be significantly associated with the COPD female patients and TNF-α-308A allele is a risk factor for the development of COPD.

The effect of elapsed time on the cardiac Troponin-T (cTnT) proteolysis in case of death due to burn: A study to evaluate the potential forensic use of cTnT to determine the postmortem interval

BACKGROUND After the death of an organism, intracellular enzymes cause protein to degrade into smaller fragments as the time passes, if these fragments can be isolated and visualized, and if the fragmentation is proved to be measurable and quantifiable, it can be a good sign of the post-mortem interval (PMI). The aim of this study is to evaluate the effect of PMI on Troponin-T protein degradation in cardiac tissues of cadavers through quantitative analysis of Troponin-T degradation by easily electrophoretic method and its association with PMI in case of deaths due to burn. METHODS An efficient extraction protocol to analyze the banding pattern of cTnT in post-mortem tissue was developed. The analysis involves extraction of the protein (at different PMI (~7.30, 18.20, 30.30, 41.20, 41.40, 54.30..................88.40h), from the heart muscles of cadavers (burn cases), separation by denaturing gel electrophoresis (SDS-PAGE) and visualization by Western blot using cTnT specific monoclonal antibodies. RESULTS The results specify a characteristic banding pattern amongst human cadavers (n=9), a pseudo-linear relationship between percent cTnT degraded and the time since death (r=0.87, p=0.0001). The area of the bands within a lane was quantified by scanning and digitizing the image using commonly available scanners. CONCLUSIONS The present research used a simple, easy, applicable and highly informative electrophoresis method that make it an ideal for the busy forensic laboratory. The post-mortem Troponin-T fragmentation observed in this study reveals a sequential, time-dependent process with the potential for use as a predictor of PMI in cases of burning. This result shows a potential for use as a future applied method of evaluating time since death.

Identification of a person with the help of bite mark analysis

Forensic dentistry is an essential part of Forensic science, mainly involves the identification of an assailant by comparing a record of their dentition (set of teeth) with a record of a bite mark left on a victim. Other uses in law for dentists include the identification of human remains, medico-legal assessment of trauma to oral tissues, and testimony about dental malpractice. While the practice of human identification is well established, validated and proven to be accurate, the practice of bite mark analysis is less well accepted. The principle of identifying an injury as a bite mark is complex and, depending on severity and anatomical location, highly subjective. Following the identification of an injury as a bite mark, the comparison of the pattern produced to a suspects dentition is even more contentious and an area of great debate within contemporary odontological practice. Like fingerprints and DNA, bite marks are unique to an individual - such as distance and angles between teeth, missing teeth, fillings and dental work. This type of impression evidence can be left in the skin of a victim and also can be in food, chewing gum and other miscellaneous items such as pens and pencils. The advent of DNA analysis and its recovery from bite marks has offered an objective method of bite mark analysis.

Association of Serum CRP level with Lung Cancer and Healthy Control of North Indian Population

BackgroundLung cancer is the major cause of cancer-related mortality worldwide. Chronic inflammation of the airway plays an important role in the alternations of bronchial epithelium and lung microenvironment, therefore provoking the pulmonary carcinogenesis and progression of lung cancer. The results may suggest that high inflammation level can be associated with the higher risk of lung cancer. CRP is an acute-phase protein produced in the liver in response to elevated cytokine levels after an inflammatory stimulus. C-reactive protein (CRP) a systemic marker of chronic inflammation is associated with increased lung cancer risk. Material and MethodologyThis case-control study was conducted on 40 lung cancer patients and 30 healthy controls. CRP level was measured in serum by ELISA kits. ResultsElevated serum CRP level was found in lung cancer patients as comparison to healthy controls. This study shows significant association between the serum CRP level of lung cancer patients and healthy controls (p<0.0001) and also showed significant association between smoker, ex-smoker and non-smokers lung cancer patients as well as in healthy controls (p<0.0001). ConclusionHigher CRP levels were found in lung cancer patients as compared to healthy controls. The higher CRP level was also observed in Smoker, Ex-smoker as compared to non-smoker in lung cancer patients and healthy control. Key-wordsLung Cancer, CRP, Inflammatory Stimulus, Cardiovascular disease, Biomarker INTRODUCTION Lung cancer is the major cause of cancer-related mortality in both men and women worldwide [1] . Chronic inflammation in airway plays an important role in the alternations of bronchial epithelium and lung microenvironment provoking the pulmonary carcinogenesis and progression of lung cancer. The results may suggest that high inflammation level can be associated with the higher risk of lung cancer. It is known that pro-inflammatory cytokines such as interleukin 1, interleukin 2, tumor necrosis factor alpha and tumor growth factor are able to stimulate the production of C-reactive protein (CRP) as well as influence survival, growth, mutation, proliferation, differentiation, and migration of tumor cells [2] . C-reactive protein (CRP) a Access this article online Quick Response Code Website:

Study on Association of BMI with Lung Cancer in North Indian Population

BackgroundLung cancer is one of the most prevalent types of cancer in India. It is considered as the most commonly diagnosed cancer and constitutes the leading cause of cancer-related mortality. The majority of lung cancer is due to smoking. Tobacco use has been reported to be one of the main causes of lung cancer. It has been observed in previous studies that excess body weight and obesity are protective factors against lung cancer in current and former smokers. MethodsThe present study recruited 235 lung cancer patients. BMI was categorized as underweight (BMI <18.5 kg/m), normal weight (BMI 18.5 to <25kg/m), overweight (BMI 25 to <30 kg/m) and obese (BMI≥30 kg/m). The study was conducted to establish the association of BMI with gender, smoking status, and histological subtypes of lung cancer. ResultsOut of 235 patients enrolled, 55.32% were underweight, 40.43% were normal weight, 3.4% of patients were classified as overweight and 0.85% was obese. This study showed a significant association of BMI with smoking status (p<0.0057), while the non-significant association with gender (p=0.75) and histological subtypes (p=0.74). ConclusionWe were concluded that significant association was found between BMI and smoking status, while non significant association was observed between BMI and gender as well as BMI and histological subtypes of lung cancer patients in the north Indian population in this study. Key-wordsBMI, Histological Subtypes, Lung Cancer, Mortality, Smoking INTRODUCTION Lung cancer is one of the most prevalent types of cancer in India and constitutes the leading cause of cancer related mortality worldwide . Lung cancer is defined as the uncontrolled cell growth of lung tissues which may lead to metastasis, invasion of adjacent tissue and infiltration beyond the lungs . The majority of lung cancer cases are due to Tobacco smoking and other environmental pollutants have been recognized as risk factors for cancer. The average five-year survival rate after diagnosis is low . It is essential to emphasize the importance of Lung Cancer prevention, and knowledge of modifiable risk factors such as environmental exposures, tobacco smoking and air pollution is prevalent among good quality epidemiological studies that explain the majority of Lung Cancer incidence . The complex interplay of etiological and psychophysical factors is believed to modify the effect of respiratory carcinogens on lung cancer initiation and prognosis . Access this article online Quick Response Code Website:

Epidermal Growth Factor Receptor Mutations detection by Mutant Specific Immunohistochemistry in North Indian Lung Cancer population

http://dx.doi.org/10.21276/IJRDPL.227 8-0238.2017.6(6).2796-2799 ABSTRACT: Background: Lung cancer is one of the leading causes of cancer-related deaths due to limited treatment options available for advanced-stage disease. The epidermal growth factor receptor is a trans-membrane glycoprotein having an extracellular epidermal growth factor binding domain and an intracellular tyrosine kinase domain which regulates signaling pathways to control cellular proliferation. Material and Methods: Detection of EGFR mutation status of 80 subjects of non-small cell lung cancer of adenocarcinoma subtype had been done by IHC using EGFR mutation specific antibodies. Results: 20 cases were positive for Del E746-A750 mutation, 6 for L858R mutation. IHC analysis shows that 30 cases scored 0, 12 cases scored 2+ and 8 cases scored 3+ in Del E746-A750 mutation while 24 cases scored 0, 1 case scored 2+ and 5 cases scored 3+ in L858R mutation. The mean age of mutation positive is 56±9.50 and negative is 53.37±11.83. 65.38% male and 34.61% female were positive for EGFR mutation. The study shows that 8 (30.77%) ex/ current smokers and 18 (69.2%) nonsmokers were positive for EGFR mutations. Conclusion: Patients who were positive for EGFR mutation can take gefitinib treatment instead of taking other chemotherapy regimen. This is a rapid method for diagnosis of lung cancer patients and helpful in the treatment decision which improve the burden of the disease. ⇑ Corresponding author at: Dr. Sandeep Bhattacharya, Department of Physiology, King George’s Medical University, Lucknow, India E-mail address: sbhattachya@gmail.com

Abstract 2222: Synergistic effects of NAT2 and GSTT1 null polymorphism in lung cancer: a study from North India

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Purpose: Polymorphism in carcinogen detoxification enzymes, NAT2 and GSTT1, has been suggested as susceptibility factor for DNA damage and lung cancer. However, little information is available on DNA adduct burden in lung tissue and polymorphisms in NAT2 and GSTs gene. We investigated the independent and combined effect of metabolic gene polymorphisms NAT2 and GSTs in lung cancer north India patients. Aim: Present study was conducted to examine: 1) whether GSTT1 Null and NAT2 genotypes have combined risk factors for Lung cancer, 2) To study possible association of tobacco smoking with NAT2 and GSTT1 null genotype of these patients. Materials and Methods: This case control study was undertaken over a period of 19 months and included 100 Lung cancer patients and 145 controls. The GSTT1 Null and NAT2 genotypes were identified by PCR-RFLP method in peripheral blood DNA samples. Genotypes frequencies and the association of the genotypes among patients and controls group were assessed by X2 test and Binary Logistic regression. Results: The NAT2 slow acetylator genotype frequency of slow or fast acetylator genotypes was not significant in lung cancer patients alone (OR = 1.18, 95% CI: 0.69 - 2.03, p value = 0.583).when we combined GSTT1Null/NAT2 slow, then we found no significant association (OR = 0.85, 95% CI: 0.47 - 1.54, p value = 0.610) between case and controls. While on comparing data with smoker as well non-smoker NAT2 polymorphism have no association but GSTT1 null have significant association (P=0.004) in smoker patients. Conclusion: These data demonstrate that there have no combined affect GSTT1 Null NAT2 slow acetylator genotype did not associated with the risk of developing lung cancer in North Indian population when compared with controls. Note: This abstract was not presented at the meeting. Citation Format: Rajni Kant Shukla, Surya Kant, Sandeep Bhattacharya, Balraj K. Mittal. Synergistic effects of NAT2 and GSTT1 null polymorphism in lung cancer: a study from North India. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2222. doi:10.1158/1538-7445.AM2014-2222

Association of Diabetic Autonomic Neuropathy with Red Blood Cell Aldose Reductase Activity

OBJECTIVE Activation of polyol pathway based on increased activity of aldose reductase (AR) has been implicated in the development of diabetic complications including diabetic autonomic neuropathy (DAN). The relationship between DAN and hyperglycemia-induced activation of polyol pathway is still uncertain. In the present study, we investigate the association between aldose reductase activity and diabetic autonomic neuropathy by measuring AR level in red blood cells (RBC). METHOD In this study, 145 subjects with diabetes with or without DAN and 32 subjects without diabetes have been included. All subjects have been investigated for autonomic function tests and RBC aldose reductase activity. DAN was defined if results of any 2 of the tests of parasympathetic function were abnormal. RBC aldose reductase level was determined spectrophotometrically and expressed as unit/g of hemoglobin. The values were expressed as mean ± standard deviation, and ANOVA test has been applied for comparison between groups. RESULTS RBC aldose reductase activity was found to be significantly higher in people with diabetes with autonomic neuropathy in comparison to people with diabetes without autonomic neuropathy and healthy individuals without diabetes. Aldose reductase (AR) level ranges from 0.8 units/g Hb to 14.2 units/g Hb. The mean AR level was 8.6±2.95 units in subjects of DM with autonomic neuropathy, while mean AR level was 4.1±1.78 units and 2.0±0.89 units in people with diabetes without neuropathy and normal healthy individuals, respectively (p<0.001). CONCLUSIONS High aldose reductase activity is associated with the presence of autonomic neuropathy in subjects of type 2 DM.

RETRACTED: Epidemiology & preventive aspects of railway suicides and fatalities related to trespassing accidents

PURPOSE Suicide and trespass are major contributors to risk on the railway, resulting in around 170-180 fatalities per year in Lucknow region, as well as associated major disruption to the rail network. Lucknow is the capital city of the state of Uttar Pradesh in India. METHODS The analysis included train-pedestrian fatalities during 2007-2012. The data for 2007-2012 were collected from the autopsy reports of the university, case sheets from the hospital, the general prosecutors investigations report and the inquest reports from police. RESULTS The results show that the majority of victims were males. Half of the suicide victims were 20-39 years old. Accidents happened most frequently in situations when a person was walking on the tracks/in front of train (22.7%) or were crossing the tracks illegally (20.9%). Among all train-pedestrian fatalities, about half of the victims (42.8%) were intoxicated by alcohol. Female suicide victims suffered from mental health problems more frequently (55.8%) than male suicide victims. CONCLUSION Overall, there is no reason to believe that train-pedestrian fatalities are unavoidable. By contrast, the effective prevention of railway suicides and accidents should be based on a systems approach involving effective measures introduces by several organisations such as government, railway organisations, various authorities (such as public health, education, enforcement, urban planning) and communities. Same measures can often be used to prevent both trespassing and suicides, even though their effectiveness may depend on the target group. In addition, there are measures specifically targeted to prevent either trespassing or suicides.