NDM-beta-lactamase-1: Where do we stand?

Multidrug-resistant (MDR) Gram-negative bacilli (GNB) have been playing havoc in the field of nosocomial as well as community-acquired infections. Of particular concern are the carbapenem-resistant GNBs, belonging to Enterobacteriaceae and encoding for New Delhi metallo-beta-lactamase-1 (NDM-1) gene. These strains spread rapidly and horizontally in the population, thus exhibiting MDR traits as these can harbour several resistance encoding genes to almost all antimicrobial groups. Several predisposing factors are responsible towards its spread, viz. excessive antibiotic usage, improper aseptic conditions by healthcare workers, lack of awareness, abruptly discontinuing medication course, alternative medications and vector-borne factors contributing to the unchecked harbouring of these super bugs in India. Thus, a bugle call has already been sounded worldwide especially in India, where the country has taken serious cognizance to build up strategy via implementation of several national programs to combat antimicrobial resistance covering human, animal, agriculture and environmental aspects. As there is an exponential rise in variants of NDM-1 harbouring strains, molecular epidemiological investigations of these strains using genotyping techniques are of paramount importance for a better understanding of this rampant spread and curbing resistance thereafter. This review explores the urgent need to develop a cost-effective, rapid molecular assay, viz. the loop-mediated isothermal amplification method for field detection of MBL harbouring bacterial strains, especially NDM-1 and its variants, thus targeting specific carbapenemase genes at a grass root level even to the remote and rural regions of the country.

Sero-Occurrence of HBV/HCV Co-infection and Levels of Liver Enzymes among Patients at a Tertiary Care Hospital in Central India: a Pilot Study.

INTRODUCTION: Hepatitis B and C viral infections share common modes of transmission and account for a large proportion of liver disease burden across the globe. Patients with Hepatitis B (HBV) and Hepatitis C virus (HCV) co-infection may have more severe liver disease and are potentially at higher risk for developing hepatocellular carcinoma. The aim of this study was to assess the sero-occurrence of HBV/HCV co-infection by examining the medical records of tertiary care hospital patients in Central India and determine the extent of liver damage based on liver function tests (LFTs). METHODS: Patients with a positive test for HBV surface antigen (HBsAg) over a period of 10 years were identified from laboratory records in a tertiary care facility in central India. Records of 51,075 consecutive non-duplicate blood samples were then screened for a positive HBV and HCV tests. LFT, liver enzymes, and bilirubin data were also extracted. Means and standard deviations were determined for continuous variables, and the difference in means was compared using a independent samples t-test. Associations between HBV/HCV co-infection status and demographic variables were calculated using Pearson's Chi-squared test. A p-value less than 0.05 was considered statistically significant. RESULTS: In this study, 1674 (3.27%) screened patients were positive for HBsAg and the sero-occurrence of co-infection with HCV in HBsAg positive patients was reported in 28 individuals (1.67%). There was no significant gender difference for HBV/HCV co-infection (p>0.05). HBV/HCV co-infection was observed more frequently in the 31-60 year old age group (p=0.001). HBV/HCV co-infected patients had significantly higher levels of liver enzymes and bilirubin than those with HBsAg mono-infection (p=0.001). CONCLUSION: Liver function tests are potentially important predictors for HBV/HCV coinfection. Screening for HCV co-infection in HBsAg-positive patients is recommended in India. Detection of co-infection may enable timely preventive/therapeutic interventions aimed at preventing progression to hepatocellular carcinoma.

Role of oxidative stress & transient receptor potential in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) affect millions of people worldwide and is known to be one of the leading causes of death. The highly sensitive airways protect themselves from irritants by cough and sneeze which propel endogenous and exogenous substances to minimize airway noxious effects. One noxious effect of these substances is activation of peripheral sensory nerve endings of nociceptor neurons innervating these airways lining thus transmitting dangerous signals from the environment to the central nervous system (CNS). Nociceptor neurons include transient receptor potential (TRP) ion channels, especially the vanilloid and ankyrin subfamilies, TRPV1/A1 which can be activated by noxious chemical challenges in models of airways disease. As oxidative stress may activate airways sensory neurons and contribute to COPD exacerbations we sought to review the role that TRP channel activation by oxidative signals may have on airway responses. i0 t would be prudent to target the TRP channels with antagonists and lower systemic oxidative stress with agents that can modulate TRP expression and boost the endogenous levels of antioxidants for treatment and management of COPD.

Insights from the Molecular Docking of Hydrolytic Products of Methyl Isocyanate (MIC) to Inhibition of Human Immune Proteins.

This study is an attempt to find the reason for immunological suppression in victims of Bhopal gas tragedy during 1984 against Mycobacterium tuberculosis (Mtb) infection. Here, we tried to understand this problem by studying interactions between immune proteins associated with susceptibility to tuberculosis and hydrolytic products of methyl isocyanate (MIC) released during the tragedy. The hydrolytic products of MIC i.e. dimethyl urea, trimethyl urea and trimethyl isocyanurate were docked to different human immune proteins against Mtb using AutoDock 4.0. Results shows that all hydrolytic products (dimethyl urea, trimethyl urea and trimethylisocyanurate) strongly inhibit to CD40 ligand, and their binding energies were found to be [Formula: see text] G [Formula: see text]3.51, [Formula: see text]3.79, [Formula: see text]4.55 (Kcal/mole), respectively. Further, to check the stability of docked complex, we performed the molecular dynamics simulation study which also shows that CD40 Ligand was maximally inhibited by trimethylisocyanurate and has a role in the macrophage activation for the destruction of M. tuberculosis. The present study may lead to better understanding of human immune protein inhibition by hydrolytic product of MIC.

Insights from the molecular docking of hydrolytic products of methyl iso cyanate (MIC) to inhibition of human immune proteins.

This study is an attempt to find the reason for immunological suppression in victims of Bhopal gas tragedy during 1984 against Mycobacterium Tuberculosis (Mtb) infection. Here we tried to understand this problem by studying interactions between immune proteins associated with susceptibility to Tuberculosis and hydrolytic products of methyl isocyanate (MIC) released during the tragedy.The hydrolytic products of methyl isocyanate (MIC) i.e. dimethyl urea, trimethyl urea and trimethyl isocyanurate was docked to different human immune proteins against Mtb using autodock 4.0. Results shows that all hydrolytic product (dimethyl urea, trimethyl urea and trimethylisocyanurate) strongly inhibits to CD40 ligand and their binding energies were found to be ΔG -3.51, -3.79, -4.55 (Kcal/Mole) respectively. Further to check the stability of docked complex we performed the molecular dynamics simulation study which also shows that CD40 Ligand was maximum inhibited by trimethylisocyanurate, has a role in the macrophage activation for the destruction of Mycobacterium tuberculosis. The present study may lead to better understanding of human immune protein inhibition by hydrolytic product of methyl isocyanate (MIC).

CD14 C-159T polymorphism and its association with chronic lung diseases: A pilot study on isocyanate exposed population of Central India.

CONTEXT: CD14 functions as a multifunctional receptor for bacterial cell wall components including endotoxin and lipopolysaccharide and is likely to influence the cytokine profile and subsequent immunoglobulin E production in response to antigen/allergen contact in allergic phenotypes. AIMS: The present study was to investigate genetic polymorphism in CD14 gene - 159C/T, which may be one of the risk factor for increased prevalence of Chronic Lung Diseases in the Central India. SETTINGS AND DESIGN: Survivors of Methyl isocyanates toxicity in Bhopal still suffering from various respiratory ailments were examined. MATERIALS AND METHODS: Polymerase chain reaction-restriction fragment length polymorphism was performed to determine the polymorphism of C-159T. RESULTS: The genotype and allelic frequencies were in Hardy-Weinberg's equilibrium. Prevalence of CC, CT, and TT were 5.5%, 22.2% and 9.25% respectively in asthmatics; 16.6%, 20.3% and 5.5% respectively in chronic obstructive pulmonary disease (COPD) patients and 5.5%, 14.8% and 1.85 respectively among interstitial lung disorder (ILD) patients; whereas the control cohort with no methyl isocyanate exposure displayed (CC, CT, and TT) cytosine, thymine as 2%, 1.6% and 2% respectively. Increased risk of Asthma among those carrying TT genotype and T allele (odds ratio [OR] =2.61 and 2.02 respectively). CONCLUSION: COPD risk significantly found among those with CC genotype and C allele (OR = 2.81 and 1.50 respectively), whereas ILD risk found significantly among CT genotype and C allele (OR = 1.75 and 1.40 respectively). Therefore, single nucleotide polymorphism (SNP) C-159T polymorphism in CD14 gene might be a risk factor for development of CLD in this population.

Association of microsatellite instability and chronic obstructive pulmonary disorder in isocyanate-Exposed population of Bhopal.

CONTEXT: Survivors of the Bhopal gas disaster still suffer from various respiratory ailments. We examined the effects of exposures among a cross-section of current residents suffering from COPD by ISSR-PCR. AIMS: Molecular screening of the gas-affected population of Bhopal with COPD for microsatellite instability due to exposure of MIC. SETTINGS AND DESIGN: The isocyanate-exposed population of Bhopal city suffering from chronic obstructive pulmonary disorder. MATERIALS AND METHODS: Inter-(SSR) analysis was used to characterize microsatellite instability in 52 MIC victims of Bhopal, suffering from COPD using (CA)(8)RG and (CA)(8)R[Y-Q] primer. STATISTICAL ANALYSIS USED: Association analyses were performed using regression analysis. RESULTS: The study on the MIC-affected population in Bhopal showed weak association between microsatellite instability and age (r = + 0.37); exposure distance from site (r = -0.44); and smoking status(r = + 0.12); while regression analysis of the above parameters displayed supporting evidence. CONCLUSIONS: The high prevalence of smoking coupled with aging and poor living habits threatens, to further increase COPD incidences among this population, highlighting the need for enhanced screening efforts.